Search

Dietary calcium supplementation has been to alter calcium metabolism and prevent hypertension in spontaneously hypertensive rats (SHR). Likewise, microgravity alters calcium metabolism. It is possible that the alteration of calcium metabolism caused by different levels of dietary calcium or microgravity change skeletal muscle properties. The purpose of this investigation was to determine whether spaceflight and/or dietary calcium causes alteration of properties in skeletal muscle from SHR. Nine-week-old male SHR, fed either high- (2.0%, HCa) or low-calcium (0.2%, LCa) diets, were flown on an 18-day shuttle flight. They were assigned to four groups (n=7/group): control (ground-based) with LCa or HCa, spaceflight with LCa, or HCa. After the spaceflight, the soleus muscle was dissected and analyzed histochemically and biochemically. Spaceflight caused a slow-to-fast fiber transition that did not differ between diet groups. Cross-sectional areas of a single muscle fiber were not modified by dietary calcium in either control or spaceflight groups. The changes of succinate dehydrogenase activity in Type I fibers in response to spaceflight was higher in the LCa diet (+23.7%) than the HCa diet group (+12.8%). Conversely, in Type IIa fibers the response to spaceflight was lower in the LCa (-9.6%) than the HCa (-19.2%) group. These findings suggest that the effect of dietary calcium on fiber type composition and fiber size may be smaller than that of spaceflight, while dietary calcium may inhibit the alteration of oxidative metabolism of muscle fibers by spaceflight in SHR.

Despite important health benefits, the presence of depressive symptoms may decrease the prevalence of breastfeeding. The current study assessed the relationship between depressive symptoms and breastfeeding at 6 and 12 weeks postpartum. Participants were recruited from a cohort completing a clinical trial of calcium for prevention of preeclampsia. At 6 weeks postpartum, the Edinburgh Postnatal Depression Scale (EPDS) was completed by mail. At 12 weeks postpartum, the EPDS was completed at an outpatient visit. There was an inverse relationship between depressive symptoms and breastfeeding at 6 weeks postpartum ( P < .001) but not at 12 weeks. This relationship persisted even after controlling for prior history of depression, increased life stress, and current psychoactive medication. The results suggest that depressive symptoms early in the postpartum period may lower the prevalence of breastfeeding.

Ground studies indicate that spaceflight may diminish vascular contraction. To examine that possibility, vascular function was measured in spontaneously hypertensive rats immediately after an 18-day shuttle flight. Isolated mesenteric resistance arterial responses to cumulative additions of norepinephrine, acetylcholine, and sodium nitroprusside were measured using wire myography within 17 h of landing. After flight, maximal contraction to norepinephrine was attenuated ( P < 0.001) as was relaxation to acetylcholine ( P < 0.001) and sodium nitroprusside ( P < 0.05). At high concentrations, acetylcholine caused vascular contraction in vessels from flight animals but not in vessels from vivarium control animals ( P < 0.05). The results are consistent with data from ground studies and indicate that spaceflight causes both endothelial-dependent and endothelial-independent alterations in vascular function. The resulting decrement in vascular function may contribute to orthostatic intolerance after spaceflight.

Nulliparous women, between 11 and 21 weeks gestation, were randomized to receive either placebo or 2,000 mg elemental calcium per day as subjects in the NIH-sponsored Calcium for Preeclampsia Prevention (CPEP) trial. Six weeks following delivery, a demographic and medical history questionnaire, and the Edinburgh Postnatal Depression Scale (EPDS), was mailed to subjects in two CPEP sites, Portland, OR and Albuquerque, NM. Subjects in the Portland site were reassessed at 12 weeks following birth. There were no statistically significant differences between treatment and placebo groups with respect to maternal demographics, history of prior depressive illness, impact of life stressors, utilization of breast-feeding, nor infant characteristics. Utilizing a standardized definition of depression (EPDS ≥ 14), chi square analysis of 293 women at 6 weeks postpartum indicated a trend (p = 0.07) toward less depression in calcium-supplemented women. Among the 247 women evaluated at 12 weeks postpartum, calcium-treated subjects had significantly less depression (p = 0.014).

Background: Chronic alcohol consumption is a major risk factor for hypertension. There is evidence in humans that the susceptibility to alcohol-related hypertension may vary based on genotype. As a first step in investigating the genetic basis for alcohol-related hypertension, the current study was designed to assess the heritability of the blood pressure response to acute ethanol exposure by using AKR/J (AK), C57BL/6J (B6), DBA/2J (D2), Balb/cJ (Balb), and A/J (A) mice. Methods: Mean arterial pressure (MAP) was recorded continuously for 24 hr in freely moving mice from an indwelling femoral catheter before we tested the effects of saline or ethanol (2 g/kg ip) on blood pressure. Results: Relative to saline, ethanol caused a pressor response that peaked within 10 min, followed by a decline in MAP. Strain A mice had a significantly greater pressor response to ethanol than other strains and did not show a decline in MAP below baseline. All other strains showed a progressive fall in blood pressure below baseline across the 60 min measurement interval. Heritability was estimated to be 0.62 for the pressor response and 0.64 for the maximal depressor response. Repeated doses of ethanol at 1 hr intervals in A and B6 mice (0,2,1.5,1.5,1.5 g/kg ip) resulted in a dose-dependent increase in MAP in A mice for the first three doses and a dose-dependent decrease in MAP in B6 mice that was independent of blood ethanol concentrations. Conclusion: The results indicate that there is a significant genetic component to the acute blood pressure response to ethanol.

Objective To compare a nutritionally complete prepared meal plan that meets national dietary guidelines to usual-care dietary therapy for hypertension, dyslipidemia, and glycemic control. Design Randomized, controlled trial. Subjects/setting Outpatients with hypertension, dyslipidemia, or diabetes mellitus (n=251) were recruited at 6 medical centers in the United States and Canada. Intervention The prepared meal plan, which was developed by university-based nutrition and cardiovascular scientists and food technologists at Campbell's Center for Nutrition & Wellness (CCNW), provided the optimal levels of macronutrients and micronutrients recommended for cardiovascular risk reduction in a variety of prepackaged meals and snacks. After a 4-week pretrial period to assess baseline state, participants were randomized to the CCNW plan or "usual-care" diet for 10 weeks. Main outcome measures Blood pressure, carbohydrate metabolism, lipoproteins, homocysteine, weight, nutrient intake, compliance. Statistical analyses performed Repeated measures analysis of variance. Results Lipoproteins, carbohydrate metabolism, blood pressure, and weight improved on both plans. Mean differences (±standard deviation) between baseline and follow-up for the CCNW plan and the usual-care plan, respectively, were total cholesterol, −0.41±0.64 and −0.20±.50mmol/L (between-group P P P =.67), diastolic blood pressure, −3.8±5.9 and −2.2±5.5mmHg ( P P P Applications/conclusion The nutritionally complete CCNW plan offers greater improvements in lipids, blood sugars, homocysteine, and weight loss than usual-care diet therapy. This prepackaged comprehensive nutrition program can augment both the prescription and practice of optimal dietary therapy. J Am Diet Assoc. 1999;99:1077–1083

OBJECTIVE: To evaluate the clinical effects of a comprehensive prepackaged meal plan, incorporating the overall dietary guidelines of the American Diabetes Association and other national health organizations, relative to those of a self-selected diet based on exchange lists in free-living individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 202 women and men (BMI < or = 42 kg/m2) whose diabetes was treated with diet alone or an oral hypoglycemic agent were enrolled at 10 medical centers. After a 4-week baseline period, participants were randomized to a nutrient-fortified prepared meal plan or a self-selected exchange-list diet for 10 weeks. On a caloric basis, both interventions were designed to provide 55-60% carbohydrate, 20-30% fat, and 15-20% protein. At intervals, 3-day food records were completed, and body weight, glycemic control, plasma lipids, and blood pressure were assessed. RESULTS: Food records showed that multiple nutritional improvements were achieved with both diet plans. There were significant overall reductions in body weight and BMI, fasting plasma glucose and serum insulin, fructosamine, HbA1c, total and LDL cholesterol, and blood pressure (P < 0.001 or better for all). In general, differences in major end points between the diet plans were not statistically significant. CONCLUSIONS: Glycemic control and cardiovascular risk factors improve in individuals with type 2 diabetes who consume diets in accordance with the American Diabetes Association guidelines. The prepared meal program was as clinically effective as the exchange-list diet. The prepared meal plan has the additional advantages of being easily prescribed and eliminating the complexities of meeting the multiple dietary recommendations for type 2 diabetes management.

Psychiatrically high-risk women were recruited for a postpartum depression prevention trial. Participants were screened at entry (20-26 weeks gestation) by a psychiatrist prior to receiving randomized treatment. Of the 31 patients who did not complete the study, 10 (33%) were dropped because of diagnosed depression. Only two women developed major depression in the postpartum period. Our data suggests, among high-risk women, obstetric care providers may be overlooking up to one fifth of women with current major depression.

Increased arterial pressure is known to be influenced by a variety of nutrients. Compliance with dietary recommendations for risk reduction is often limited by the complexity of their implementation. In addition, how improvements in total diet, rather than single nutrients, influence concomitant cardiovascular risk factors has not been thoroughly explored. We assessed the effects of a nutritionally complete prepared meal program, the Campbell's Center for Nutrition and Wellness plan (CCNW), compared with dietary therapy in which participants received a structured nutritional assessment and prescription and selected their own foods, in 101 women and men with mild-to-moderate hypertension. Outcome measures included blood pressure (BP), lipids and lipoproteins, glucose, glycosylated hemoglobin (HbA1c), insulin, homocysteine, nutrient intake, compliance, and quality of life. Both dietary interventions significantly lowered BP (P < .0001), while simultaneously improving the overall cardiovascular risk profile. Significantly greater benefits were observed with the CCNW plan as compared with the participant selected diet in cholesterol and LDL levels (both P < .0001), LDL:HDL (P < .001), HbA1c (P < .05), homocysteine (P < .001), total nutrient intake (P < .0001), compliance (P < .0001), and quality of life (P < .001). This study demonstrates that improving the total diet to include the full array of recommended dietary guidelines, rather than focusing on single nutrients, has significant benefits for the cardiovascular risk profile of hypertensive persons beyond BP control. Compared with typical dietary therapy, the comprehensive CCNW meal plan has significantly greater effects on multiple cardiovascular risk factors while yielding greater compliance and improved quality of life.

Many vasoactive elements are involved in the elevation of blood pressure in spontaneously hypertensive rats (SHR). Elevated dietary calcium has been observed to reduce blood pressure in SHR. This study investigates interactions among dietary calcium, renal vascular resistance (RVR), elevation of blood pressure and effects of norepinephrine and nitric oxide synthesis. We completed a series of experiments on two groups each (fed low, 0.1% and high, 2.0% dietary calcium, respectively) of 9-week-old Wistar Kyoto (WKY), 9-week-old and 6-week-old SHR. Although 9-week-old SHR had elevated baseline blood pressure compared to 9-week-old WKY and also compared to 6 week-old SHR, there was no corresponding elevation in baseline RVR. All SHR fed high calcium diets had lower blood pressure compared to low calcium diets, and there was no corresponding reduction in RVR. WKY controls' blood pressure and RVR were unaffected by dietary calcium levels. In all hypertensive rats the blood pressure and renal vascular resistance were elevated by NG-nitro- l -arginine methylester ( l -NAME), but the dietary differences were sustained. Blood pressure of WKY was unaffected by the low dose of l -NAME. The increase in RVR to l -NAME was greater in SHR than in controls. The renal vascular response to norepinephrine was related to diet in older SHR, but smaller and unrelated to diet in younger SHR. Following l -NAME, WKY had greater responses to norepinephrine than 9-week-old SHR. We conclude that noradrenergic vasoconstriction is enhanced in the adult SHR, especially in the absence of high calcium diet. Alterations in NO synthesis may effect the norepinephrine response.

Spontaneously hypertensive rats (SHR) are known to be blood pressure sensitive to dietary calcium. The effects of dietary calcium on platelet aggregation and intracellular Ca2+ mobilization were assessed by turbidimetric methods and fura-2 methods, respectively, in washed platelets of SHR. Ca2+ ATPase activity was examined in aortic membrane fractions. Six weeks of dietary calcium supplementation attenuated the increase of systolic blood pressure (SBP 199 +/- 16 v 170 +/- 9 mm Hg, P < .001) and thrombin-induced platelet aggregation (84.5 +/- 3.7 v 73.7 +/- 7.4%, P < .004) at 9 weeks of age. The ionomycin-induced intracellular calcium ([Ca2+]i) peak in the absence of external Ca2+, which reflects [Ca2+]i storage size, and thrombin-evoked [Ca2+]i release from [Ca2+]i storage were decreased by 2.0% Ca diet (472 +/- 55 v 370 +/- 23 nmol/L, P < .001, 339 +/- 29 v 278 +/- 33 nmol/L, P < .002). In addition, SBP was positively correlated with platelet aggregation (r = 0.703, P = .0088), thrombin-evoked [Ca2+]i (r = 0.739, P = .0044), and ionomycin-induced [Ca2+]i (r = 0.591, P = .0415), respectively. However, there was no significant effect of dietary calcium on Ca2+-ATPase activity in aortic membranes. These results suggest that dietary calcium supplementation had a beneficial effect on platelets of SHR by attenuating [Ca2+]i mobilization from [Ca2+]i storage. The hypotensive effect of dietary calcium might be associated with attenuated [Ca2+]i mobilization in SHR.

Noncompliance with therapeutic diets remains a major obstacle to achieving improvements in cardiovascular disease (CVD) morbidity and mortality. This study compared dietary compliance and CVD risk factor response to two dietary interventions designed to treat hypertension, dyslipidemia, and diabetes mellitus. In a multicenter trial, 560 adults were randomly assigned to either a self-selected, mixed-food plan (n = 277), or a nutrient-fortified prepared meal plan (n = 283); each was designed to provide 15-20% of energy from fat, 55-60% from carbohydrate, and 15-20% from protein. Nutrient intake was estimated from 3-d food records collected biweekly throughout the 10-wk intervention. Compliance was determined by evaluating the participants' ability to meet specific criteria for energy intake [+/-420 kJ (100 kcal) from the midpoint of the prescribed energy range], fat intake (< 20%, < 25%, or < 30% of energy from total fat), and the National Cholesterol Education Program/American Heart Association Step 1 and 2 diet recommendations. Compliance with energy, fat, and Step 1 and 2 criteria was better in participants who followed the prepared meal plan than in those who followed the self-selected diet (P < 0.0001). Compliant participants in both groups achieved greater reductions in body weight, systolic and diastolic blood pressure, and total and low-density-lipoprotein cholesterol than noncompliant participants (P < 0.05). In general, better endpoint responses were observed with lower fat intakes regardless of group assignment. The prepared meal plan is a simple and effective strategy for meeting the many nutrient recommendations for CVD risk reduction and improving dietary compliance and CVD endpoints.

Borderline hypertensive rats (BHR) were used to test the hypothesis that baroreflex resetting prevents a fall in blood pressure (BP) when cardiac output (CO) is reduced during air-jet stress. Eight-week-old BHR were instrumented with flow probes around the ascending aorta for measuring CO, femoral and jugular catheters were inserted for measurement of arterial pressure and infusion of drugs, and sinoaortic baroreceptors were either denervated (SAD) or left intact. Alternating bolus injections of phenylephrine and sodium nitroprusside were given at baseline and during air-jet stress to assess the baroreflex. Air-jet stress immediately shifted the midpoint of the baroreflex curve for heart rate (HR) to a higher BP levels. When metoprolol was administered during air-jet stress, HR was reduced and CO reverted to prestress levels, but the stress-induced pressor response was not changed. In SAD BHR, air-jet stress caused an elevation of BP that was not different from intact rats. Administration of metoprolol to SAD rats during air-jet stress resulted in a further elevation rather than a reduction in BP. We conclude that the sinoaortic cardiac baroreflex is reset during air-jet stress and that it integrates reflex changes in BP during stress. The arterial baroreflex is not, however, necessary for the initiation or maintenance of the pressor response during stress, nor does it prevent a fall in BP when CO is compromised during stress.

Background: Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet. Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction. Objective: To assess the clinical effects of this plan, which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins, minerals, and macronutrients, compared with a patient-selected American Heart Association Step I and Step II diet plan. Methods: This multicenter, randomized, parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension, dyslipidemia, or diabetes. Following calculation of prescriptions to meet individual nutritional requirements based on the HarrisBenedict equation, participants were randomized to the Campbell's Center for Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast, lunch, and dinner meals provided to participants, or a nutritionist-guided American Heart Association Step I and Step II diet, in which participants self-selected foods to meet their nutrition prescription for 10 weeks. Main Outcome Measures: Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c), and insulin levels; body weight; dietary intake; and quality of life. Results: Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life (P≤.001 for all findings except low-density lipoprotein-high-density lipoprotein ratio,P=.25) all improved on both nutrition plans. Mean differences (±SD) between baseline and treatment clinical values for the CCNW and the self-selected diet groups (between-groupPvalues), respectively, were as follows: systolic BP, -6.4±9.2 mm Hg and -4.6±9.0 mm Hg (P=.02);ic BP, -4.2±5.7-4.2±5.7 -3.0±5.1 m-3.0±5.1 mm Hg (P=.006)rol, -0.32±0.58-0.32±0.58 mmol/L and -0.27±0.56 mmol/L(-12.4±22.5 mg/dL and -10.4±21.9 mg/dL) (P=.30); glucose, -0.65±1.88 mmol/L andm-0.75±2.03 mmol/L (-11.7±34.0 mg/dL and -13.5±36.6 mg/dL) (P=.10); and HbA1c, -0.4%±0.8% and -0.3%±0.7% (P=.66). Weight loss with the CCNW and self-selected plans, respectively, was as follows: men, -4.5±3.6 kg and -3.5±3.3 kg; and women, -4.8±3.0 kg and -2.8±2.8 kg. Quality of life was significantly improved for daily and work activities (P Conclusions: Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease. The CCNW plan resulted in greater clinical benefits, nutritional completeness, and compliance than the self-selected diet. The CCNW is a comprehensive nutrition plan, convenient for both prescription and practice, and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease. disease. Arch Intern Med. 1997;157:169-177

The association between dietary calcium intake, calcium metabolism, and blood pressure form the basis of this review. Epidemiologic data consistently show an inverse relationship between dietary calcium and blood pressure. Clinical trials of calcium supplementation have not been as consistent in outcome. Approximately two-thirds of the supplementation studies have found a beneficial effect of calcium on blood pressure. The lack of consistency in outcome from the clinical trials relative to the epidemiological literature may be related to calcium intake. The epidemiological literature indicates an inverse relationship between calcium intake and blood pressure, with those individuals with the lowest calcium intake ( 700 mg/day) may not see an effect of calcium supplementation on blood pressure because of a ceiling effect. Supplemental calcium appears to correct a defect in calcium handling characterized by a renal calcium leak, increased circulating parathroid hormone, and increased intracellular calcium levels. In part, the deficit in cellular calcium homeostasis may be a consequence of abnormal calmodulin activity. Specifically, it appears that calmodulin activity is diminished in experimental hypertension and that increasing dietary calcium may improve calmodulin activity in the spontaneously hypertensive rat. The deficit in calmodulin activity has the potential to interfere with a number of cellular processes crucial to the regulation of cell function and maintenance of appropriate vascular tone. It is concluded that additional research should be directed toward understanding the ramifications of altered calmodulin activity in hypertension and the influence that dietary calcium can have on the activity of calmodulin.Key words: hypertension, dietary Ca2+, calmodulin, Ca2+ metabolism, calcium channel blockers.

More than 80 studies have reported lowered blood pressure after dietary calcium enrichment in experimental models of hypertension. The evidence presented here suggests that dietary calcium may act concurrently through a number of physiological mechanisms to influence blood pressure. The importance of any given mechanism may vary depending on the experimental model under consideration. Supplemental dietary calcium is associated with reduced membrane permeability, increased Ca(2+)-ATPase and Na,K-ATPase, and reduced intracellular calcium. These results suggest that supplemental calcium may limit calcium influx into the cell and improve the ability of the VSMC to extrude calcium. This could be a direct effect of calcium on the VSMC or an indirect effect mediated hormonally. The calcium-regulating hormones have all been found to have vasoactive properties and therefore may influence blood pressure. Furthermore, CGRP and the proposed parathyroid hypertensive factor are both vasoactive substances that are responsive to dietary calcium. Therefore, diet-induced variations in calcium-regulating hormones may influence blood pressure. Modulation of the sympathetic nervous system is another important way that dietary calcium can influence blood pressure. There is evidence of altered norepinephrine levels in the hypothalamus as a consequence of manipulations of dietary calcium as well as changes in central sympathetic nervous system outflow. Dietary calcium has also been shown to specifically modify alpha 1-adrenergic receptor activity in the periphery. In some experimental models of hypertension, dietary calcium may alter blood pressure by changing the metabolism of other electrolytes. For example, the ability of calcium to prevent sodium chloride-induced elevations in blood pressure may be attributed to natriuresis. However, natriuresis does not account for all of the interactive effects of calcium and sodium chloride on blood pressure. Sodium chloride-induced hypertension may be due in part to calcium wasting and subsequent elevation of calcium-regulating hormones. Chloride is an important mediator of this effect because it appears that sodium does not cause calcium wasting when it is not combined with chloride. More attention to the central nervous system effects of dietary calcium is needed. Not only can calcium itself influence neural function, but many of the calcium-regulating hormones appear to affect the central nervous system. The influence of calcium and calcium-regulating hormones on central nervous system activity may have important implications for blood pressure regulation and also may extend to other aspects of physiology and behavior.

Blood pressure and circulating catecholamines were evaluated in borderline hypertensive rats (BHR) that were exposed to daily sessions of either short (20 min) or long (120 min) duration air-jet stimulation. Indirect measures of systolic blood pressure indicated that within 2 weeks both experimental groups developed stress-induced hypertension in comparison to home cage controls. Animals exposed to 120 min stress sessions had significantly higher systolic blood pressure relative to the 20 min group. However, direct measures of blood pressure taken after 5 weeks of daily stress did not reveal any differences between the stress groups. Daily measurements indicated that acute changes in blood pressure during stress were modest and transient, suggesting little contribution to the chronic elevation in blood pressure observed as a consequence of stress. Circulating catecholamines were significantly increased by the stressor. Epinephrine returned to baseline within 60 min, although norepinephrine remained elevated throughout the 120 min session. The results indicate that increasing the duration of daily air jet stimulation did not impact the development of stress-induced hypertension over the 5-week measurement period.

The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat. In response to acute environmental stress (air jet), the borderline hypertensive rat exhibits a diuretic response, whereas the parental strains exhibit an antidiuretic response (spontaneously hypertensive rat) or no change in urine flow rate (Wistar-Kyoto rat). This study sought to investigate the role of the periventricular tissue surrounding the anteroventral third ventricle and vasopressin release in the diuretic response of the borderline hypertensive rat to acute environmental stress. Sixteen-week-old borderline hypertensive rats who had consumed a 1% NaCl diet for 10-12 weeks were given either electrolytic lesions of the anteroventral portion of the third ventricle or sham lesions. When exposed to acute environmental stress 4 weeks later, the increase in volume of dilute urine seen in the sham-lesion rats was not observed in the lesion rats. Plasma vasopressin concentration was decreased by acute environmental stress in the sham-lesion rats (15.2 +/- 4.0 to 10.9 +/- 1.7 pg/ml, p less than 0.05) but was unchanged in the lesion rats (12.3 +/- 2.0 to 13.4 +/- 4.0 pg/ml). In a separate group of intact borderline hypertensive rats, a constant intravenous infusion of vasopressin prevented the diuretic response to acute environmental stress. The results suggest that acute environmental stress produces a diuresis in the borderline hypertensive rats via a decrease in plasma vasopressin concentration that is dependent on the integrity of the periventricular tissue of the anteroventral portion of the third ventricle.

This study investigated possible mechanisms for the hypotension produced by nitroprusside infusion in conscious dogs pretreated with a V1 vasopressin antagonist. The hypothesis that an action of vasopressin at V2-like receptors contributes to the hypotension was tested by comparing the effects of a V1 antagonist to the effects of a combined V1/V2 antagonist. Nitroprusside infusion produced dose-dependent decreases in arterial and atrial pressures. Larger decreases in pressures were produced in animals pretreated with either antagonist; however, the decreases in V1/V2-blocked dogs were not less than the decreases in V1-blocked dogs. These data suggest that V2-like actions of vasopressin do not contribute to the hypotensive effects of V1 blockade. A second hypothesis was that the greater hypotension was due to activation of a cardiac reflex to cause withdrawal of sympathetic tone, a decrease in peripheral resistance, and adrenal activation. Measurement of cardiac output revealed that the larger decreases in arterial pressure were due to larger decreases in total peripheral resistance. The hypotension was also associated with decreases in heart rate, unchanging plasma norepinephrine concentration, and increases in epinephrine concentration. These data are consistent with the hypothesis that the fall in pressure observed in dogs pretreated with a V1 antagonist is secondary to a decrease in peripheral resistance that is due at least in part to withdrawal of sympathetic tone.

Supplemental dietary calcium in spontaneously hypertensive rats (SHRs) aged 21-28 d produces a decrease in blood pressure and hematocrit. The simultaneous fall in hematocrit and blood pressure suggests that the changes in blood pressure may be, in part, a consequence of the decrease in hematocrit and reduction in viscosity. To examine this possibility, SHRs aged 21 d were placed on one of four diets varying in iron content. At age 28, the animals showed iron-induced variations in hematocrit (P less than 0.001) but no difference in blood pressure. Subsequent manipulation of the ratio of calcium and iron in the diets of additional groups of animals resulted in variations in hematocrit that were independent of the calcium-induced alterations in blood pressure. We conclude that the effects of calcium on blood pressure are relatively independent of its effects on hematocrit.

Salt-sensitive spontaneously hypertensive rats (SHR) and their normotensive control strain, Wistar-Kyoto rats (WKY) were fed four diets varying in sodium chloride and calcium content in order to assess the effects of diet on learned blood pressure responses. The animals were exposed to a classical conditioning paradigm in which one tone was always followed by a brief electric shock and a second tone was never followed by shock. Sodium chloride loading raised baseline blood pressure in both strains, while supplemental calcium attenuated blood pressure. Sodium chloride potentiated blood pressure orienting responses to initial presentations of the tones among calcium deficient, but not calcium replete SHR. Increased sodium chloride intake also potentiated the learned pressor responses to the tone paired with shock in the SHR, but not the WKY. Calcium intake had no apparent effect on the learned blood pressure responses to the two tones.

We found in mice that repeated single daily subcutaneous (s.c.) isoproterenol (ISO) injections, like constant infusions using osmotic minipumps, caused increased biventricular mass or weight relative to body weight (VW/BW). We found that 5 (1/d) s.c. injections of 2, 10, or 20 µg/g body weight caused equivalent VW/BW increases as compared with 5-d infusions at 20 µg/(g·d)). While it is often presumed that ISO elicits hypertrophy by a direct effect on the myocytes, growth may also be secondary to systemic hemodynamic effects. The 2 modes of ISO administration had different effects on mean arterial blood pressure (MABP) and heart rate. Using telemetry we observed that single injections of ISO (0, 0.5, 2, and 10 µg/g) were associated with hypotension and tachycardia with a duration but not a magnitude that was dose dependent. MABP dropped rapidly to 60 mm Hg for more than 2 h at the highest dose. Constant s.c. infusion of ISO at 20 µg/(g·d) initially lowered MABP to about 70 mm Hg for 24 h. At 48 h MABP was normal, but rose 10 mm Hg higher than baseline by day 5. Thus, different routes of administration of ISO that cause comparable increases in VW/BW had different effects on MABP. Thus when evaluating mouse models of ISO-induced cardiac hypertrophy, both repeated daily injections or infusions can cause similar increases in VW/BW, but the daily doses that are required are not the same. Furthermore, these different routes of administration have different hemodynamic sequelae and could potentially evoke different cardiac phenotypes.Key words: C57BL6 mouse, hypotension, heart rate, cardiac hypertrophy, β-adrenergic.

Thyroxine (T(4)) is the predominant form of thyroid hormone (TH). Hyperthyroidism, a condition associated with excess TH, is characterized by increases in metabolic rate, core body temperature and cardiac performance. In target tissues, T(4) is enzymatically deiodinated to 3,5,3'-triiodothyronine (T(3)), a high-affinity ligand for the nuclear TH receptors TR alpha and TR beta, whose activation controls normal vertebrate development and physiology. T(3)-modulated transcription of target genes via activation of TR alpha and TR beta is a slow process, the effects of which manifest over hours and days. Although rapidly occurring effects of TH have been documented, the molecules that mediate these non-genomic effects remain obscure. Here we report the discovery of 3-iodothyronamine (T(1)AM), a naturally occurring derivative of TH that in vitro is a potent agonist of the G protein-coupled trace amine receptor TAR1. Administering T(1)AM in vivo induces profound hypothermia and bradycardia within minutes. T(1)AM treatment also rapidly reduces cardiac output in an ex vivo working heart preparation. These results suggest the existence of a new signaling pathway, stimulation of which leads to rapid physiological and behavioral consequences that are opposite those associated with excess TH.

The current study examined the relationship between calcium supplementation during pregnancy and blood pressure (BP) in the mother and offspring at 3 months and at 2 years postpartum.Nulliparous pregnant women were assigned to either receive 2 g of calcium or placebo daily beginning between weeks 13 to 21 of gestation and continuing until delivery. Blood pressure was measured in children and their mothers at 3 months (n = 260) and (n = 57) at 2 years postpartum. Systolic BP was measured in the infants using a sphygmomanometer with ultrasonic amplification. For the toddlers, three supine BP measurements were taken from the right arm using a Critikon automated sphygmomanometer just after measurement of left ventricular wall thickness.Systolic BP in the calcium-supplemented infants was 2.2 mm Hg lower than in the placebo group (P.05). At 2 years of age, systolic BP was 4.8 mm Hg lower in the calcium supplemented group (P.05), whereas diastolic BP was 3 mm Hg lower (P.05). There was no difference in left ventricular mass index between groups, although there was a significant correlation between systolic BP and wall thickness (P.05). Maternal BP was positively correlated with circulating 1,25(OH)(2)D3 (P.001) but did not differ between calcium groups at 3 months postpartum.The data on BP in the children are in agreement with previous studies and argue strongly for additional research into the effects of prenatal calcium supplementation on BP regulation in the offspring.

To study physiologic factors affecting the blood pressure (BP) response to nonpharmacologic maneuvers, fasting blood glucose, insulin, lipid and mineral levels, urinary mineral excretion, and the calcium regulating hormones parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D (1,25 (OH)2D) were measured in 71 unmedicated hypertensive (26 hypertensive only [HT], 45 hypertensive hyperlipidemic [HTHL]), and 87 normotensive hyperlipidemic (NTHL) control subjects before and during a 10-week multicenter, randomized controlled trial comparing a prepared meal plan (CCNW) with a self-selected diet (SSD) based on nutritionist counseling. Blood pressure fell to a greater extent in hypertensive versus normotensive subjects (-8+/-1/-5+/-1 v -2+/-1/-2+/-1 mm Hg, P < .0001/P < .0001), and on CCNW versus SSD diets (delta systolic BP [SBP]/delta diastolic BP [DBP], P = .033/P = .002). Diet-induced weight change was the strongest correlate of changes in BP (SBP: r = 0.360, P < .0001; DBP: r = 0.414, P < .0001), which, on multivariate analysis for deltaSBP, could partly be accounted for by diet-induced changes in fasting glucose (r = 0.215, P = .009) and cholesterol (r = 0.219, P = .006) levels. Independently of weight, diet-induced changes in SBP also were significantly related to concomitant changes in urinary excretion of potassium (r = -0.285, P = .001), magnesium (r = -0.254, P = .003), and calcium relative to sodium (r = -0.200, P = .021), but not to sodium per se; and to changes in serum potassium (r = -0.249, P = .002), phosphorus (r = -0.279, P = .001), PTH (r = 0.288, P = .0006), and 1,25 D (r = 0.202, P = .017). We conclude that the ability of diet to lower BP successfully may result from the additive contributions of multiple components. Independently of weight loss and the associated changes in circulating glucose and cholesterol, BP is influenced by the increasing provision of minerals such as potassium, magnesium, and calcium, perhaps by virtue of their suppressive effects on circulating vasoactive calcium regulating hormones.

The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine1 and behavioural responses to stress2, and the related hormone urocortin3 (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2 (refs 4,5). These receptors may exhibit distinct functions due to unique tissue distribution6 and pharmacology4,5. Crhr-null mice have defined central functions for Crhr1 in anxiety and neuroendocrine stress responses7,8. Here we generate Crhr2−/− mice and show that Crhr2 supplies regulatory features to the hypothalamic-pituitary-adrenal axis (HPA) stress response. Although initiation of the stress response appears to be normal, Crhr2−/− mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive. Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2−/− mice. In addition, stress-coping behaviours associated with dearousal are reduced in Crhr2–/– mice. We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn. Feeding is initially suppressed in Crhr2−/− mice following Ucn, but Crhr2−/− mice recover more rapidly and completely than do wild-type mice. In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2−/− mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects. Moreover, Crhr2−/− mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis. Our results identify specific responses in the brain and periphery that involve Crhr2.

BACKGROUND Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-micromol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater. OBJECTIVE Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease. DESIGN This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/=100% of the recommended dietary allowances for 23 micronutrients, including folate. RESULTS Mean folate intakes at 10 wk were 601 +/- 143 microgram/d with the PMP and 270 +/- 107 microgram/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/- 5.8 to 9.3 +/- 4.9 micromol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD. CONCLUSIONS The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease.

The hypothesis that long-term increases in angiotensin II (ANG II) produce pressure-independent resetting of baroreflex control of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis was tested in rabbits by determining the effect of chronic ANG II infusion on reflex relationships between mean arterial pressure (MAP) and plasma concentrations of norepinephrine (NE) and corticosterone (CS). After 2 wk, ANG II increased MAP from 61 +/- 1 to 99 +/- 2 mmHg (P < 0.05) without altering heart rate or plasma NE concentration, but increased CS from 9.8 +/- 1.3 to 29.5 +/- 13.7 ng/ml (P < 0.05). Heart rate, NE, and CS baroreflex curves were all reset to a higher pressure level (P < 0.05) after 24 h, 1 wk, and 2 wk of ANG II. Forty minutes after stopping ANG II on the same days, MAP decreased, and curves were shifted back toward control (P < 0.05), indicating that ANG II was required for the resetting. Two findings suggest that the resetting action ofANG II is distinct from the pressor effect. First, although stopping ANG II reversed the hypertension as it reversed the resetting, reversal of the hypertension instead by prolonged infusion of nitroprusside along with ANG II did not have the same effect. Second, NE and heart rate baroreflex curves returned toward preinfusion positions after stopping ANG II (P < 0.05), even when the hypertension was nearly maintained by phenylephrine infusion. In conclusion, chronic increases in ANG II may have a global baroreflex resetting effect by a mechanism that is in part independent of the hypertension.

OBJECTIVE To determine the effect of chronic alcohol consumption upon blood pressure, blood pressure reactivity and vascular contractility in Wistar rats. DESIGN Wistar rats were fed a liquid diet containing 36% ethanol; control rats were pair fed. METHODS Rats were maintained on diets for 18 weeks. Indirect systolic blood pressure was measured weekly. Catheters were implanted for assessment of direct arterial pressure and blood pressure reactivity to norepinephrine, angiotensin II and ethanol injections. In a subgroup of rats, contractility of isolated mesenteric resistance vessels was measured. RESULTS In comparison with simultaneously pair-fed controls, ethanol-treated rats developed significantly lower blood pressure within 3 weeks of exposure to alcohol; this continued throughout the study. Despite the reduction in blood pressure, in vitro assessment of vascular contractility in mesenteric resistance vessels indicated that ethanol consumption significantly enhanced vascular contractility to norepinephrine and attenuated the vasodepressive effects of ethanol. Measurement of blood pressure reactivity to infused pressor agents showed no difference between controls and ethanol-treated rats in response to norepinephrine but a significantly attenuated pressor response to angiotensin II was observed in ethanol-treated rats. CONCLUSIONS The blood pressure results contrast with reports of elevated blood pressure in Wistar rats given ethanol in drinking water. This disparity may be due to nutritional factors. Increased vascular contractility combined with hypotension suggests that cardiovascular regulatory systems offset the direct effects of ethanol upon the vasculature. This view is reinforced by the lack of difference between groups in blood pressure reactivity to norepinephrine. The attenuated angiotensin II responses in the ethanol-treated rats suggests altered levels of circulating angiotensin II in this group.

To assess the long-term effects of a prepackaged, nutritionally complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss and cardiovascular risk factors in overweight and obese persons.In this randomized multicenter study, 302 persons with hypertension and dyslipidemia (n = 183) or with type 2 diabetes mellitus (n = 119) were randomized to the nutrient-fortified prepared meal plan (approximately 22% energy from fat, 58% from carbohydrate, and 20% from protein) or to a macronutrient-equivalent UCD.The primary outcome measure was weight change. Secondary measures were changes in blood pressure or plasma lipid, lipoprotein, glucose, or glycosylated hemoglobin levels; quality of life; nutrient intake; and dietary compliance.After 1 year, weight change in the hypertension/dyslipidemia group was -5.8+/-6.8 kg with the prepared meal plan vs -1.7+/-6.5 kg with the UCD plan (P.001); for the type 2 diabetes mellitus group, the change was -3.0+/-5.4 kg with the prepared meal plan vs -1.0+/-3.8 kg with the UCD plan (P.001) (data given as mean +/- SD). In both groups, both interventions improved blood pressure, total and low-density lipoprotein cholesterol levels, glycosylated hemoglobin level, and quality of life (P.02); in the diabetic group, the glucose level was reduced (P.001). Compared with those in the UCD group, participants with hypertension/dyslipidemia in the prepared meal plan group showed greater improvements in total (P.01) and high-density lipoprotein (P.03) cholesterol levels, systolic blood pressure (P.03), and glucose level (P.03); in participants with type 2 diabetes mellitus, there were greater improvements in glucose (P =.046) and glycosylated hemoglobin (P.02) levels. The prepared meal plan group also showed greater improvements in quality of life (P.05) and compliance (P.001) than the UCD group.Long-term dietary interventions induced significant weight loss and improved cardiovascular risk in high-risk patients. The prepared meal plan simultaneously provided the simplicity and nutrient composition necessary to maintain long-term compliance and to reduce cardiovascular risk.

LEARNING OUTCOME: To assess the quality of life outcomes from two methods for achieving the NCEP/AHA Step 1/2 dietary guidelines. Health professionals frequently advise patients with cardiovascular diseases to modify their diets but often find that patients do not follow their advice because of difficulties encountered altering food-intake patterns. Finding ways of reducing the difficulties associated with dietary change is of critical importance to successful nutritional therapy. The objective of this study was to provide a complete-prepared food plan as a means of reducing diet-related difficulties. Success in meeting this objective was measured by improvements in quality of life (QOL). The prepared food plan was compared to an intensive dietitian-guided, self-selected diet. Both meal plans provided as %Kcal

Objective : Daily exposure to air-jet stress (AJS) causes sustained elevations of blood pressure in borderline hypertensive rats (BHR). It is known that the renin-angiotensin system is activated during episodes of behavioral stress, and the purpose of this study was to assess the involvement of renin-angiotensin system in the development of stress-induced hypertension in the BHR. Design : Four groups of 8- and 9-week-old rats were studied : they received, respectively, oral captopril and AJS ; oral captopril without AJS ; AJS without captopril ; and neither AJS nor captopril. Methods : After 10 days of AJS and captopril conditions, femoral and jugular catheters were implanted for the measurement of mean arterial pressure and pressor responses to norepinephrine and tyramine. Blood samples were collected for the measurement of norepinephrine and plasma renin activity. Results : Ten days of AJS caused a significant elevation of blood pressure in BHR exposed to AJS without receiving captopril but not in those animals given captopril concurrently with AJS. Circulating norepinephrine and blood pressure responses to exogenous norepinephrine and tyramine were similar across the four groups. Plasma renin activity was highest in BHR given captopril, and was significantly elevated during an acute episode of AJS. Conclusions : The renin-angiotensin system may be important in the development of stress-induced hypertension in the BHR.

Plasma catecholamine levels were measured preceding programmed electrophysiological studies of patients who had survived a ventricular tachyarrhythmia episode. Psychological assessments of desire for control, locus of control and behavior pattern were obtained. Psychophysiological variables were analysed with respect to the severity of arrhythmias induced by the electrophysiological procedure. Analysis of data from 17 subjects showed desire for control was significantly higher in those with induced sustained arrhythmias than in those in which nonsustained arrhythmias were induced. No relationship was found between behavior pattern and arrhythmia severity or plasma catecholamine levels. There was a significant interaction between desire for control and behavior pattern with respect to epinephrine level. The findings indicate that psychological factors such as desire for control may be associated with potentially lethal arrhythmias and implicated in sudden cardiac death.

The present study was performed to determine the effects of the anticholinergic agent scopolamine and the cholinergic agent physostigmine on tonic immobility in rabbits. Recordings of the electroencephalographic (EEG) activity from cortex and hippocampus were also made before, during, and after each test session. Scopolamine significantly prolonged the response and produced large amplitude slow wave activity in the EEG of both cortex and hippocampus. Physostigmine significantly shortened the duration of immobility and increased rhythmic slow activity in the frequency range of 5.5-9.1 Hz in the hippocampus while producing a desynchronized cortical rhythm. It is suggested that the cortex and hippocampus play a role in modulating tonic immobility duration by inhibiting the brain-stem structures thought to control this response.

It has been hypothesized [ B. Lofving, 1961, Acta Physiologica Scandinavica (Suppl) 53, 184 ; W. R. Klemm, 1971, In S. Ehrenpreis & O. C. Solnitzky, Eds., Neurosciences Research, Vol. 4, New York: Academic Press ; D. C. Hatton, T. Lanthorn, D. Webster, & M. E. Meyer, 1975, Behavioral Biology, 22, 122–127 ] that baroreceptor activity, as a consequence of postural inversion and restraint, plays a major role in the induction of the immobility reflex in rabbits. To investigate that hypothesis, blood pressure and heart rate were recorded from normal rabbits and rabbits with their carotid sinus denervated during induction and termination of the immobility reflex. The results indicated that a baroreceptor reflex occurred with postural inversion as measured by amount of bradycardia and the relative fall in blood pressure. There were significant differences in the pattern of the heart rate and blood pressure response between induction and termination for all animals. There were also significant differences between normal and denervated animals in their blood pressure response to inversion and termination. The results support the hypothesis that reflexive baroreceptor activity occurs as a consequence of the induction procedure for immobility.

Wallnau and Gallup ( L. B. Wallnau and G. G. Gallup, 1977, Biobehav. Rev. 1 , 35–43 ) recently proposed a serotonergic midbrain raphe model of tonic immobility (TI), wherein there is an inverse relationship between raphe activity and the duration of TI. In part, this model was based on the results of central and peripheral injections of serotonin in chickens which increase and decrease TI, respectively. In rats, centrally administered serotonin depresses raphe firing ( G. K. Aghajanian, 1972, Fed. Proc. 31 , 91–96 ) while peripherally administered serotonin potentiates raphe firing ( S. Mosko and B. L. Jacobs, 1974, Brain Res. 79 , 315–320 ). The present investigation examined the effect of central and peripheral injections of serotonin on the duration of TI in rabbits. The results were not in agreement with Wallnau and Gallup's predictions. The data suggest that serotonergic influences on TI vary across species.

Heart rate (HR) responses of restrained spontaneously hypertensive (SHR) and normotensive (WKY) female rats were compared during aversive classical conditioning. Baseline HR of the SHR group was temporarily higher than that of the WKY group. For both groups, the directions of the HR-orienting response to the novel CS prior to conditioning as well as the HR-conditioned response during conditioning were decelerative. Although the magnitude of the orienting response was larger in the SHR group than in the WKY group, the conditioned responses of the two groups were nearly the same. It was suggested that the orienting response in both groups was due to inhibition of sympathetic activity in conjunction with increased vagal outflow. It was further suggested that the enhanced orienting response in the SHR group could be accounted for by the greater β-adrenergic tone in the resting HR of the SHR which, with inhibition of sympathetic tone, resulted in a relatively larger fall in HR.

The present study was performed to test the effects of the anticholinergic drug scopolamine and the cholinergic-potentiating drug physostigmine on tonic immobility (TI) in ducks and guinea pigs. Scopolamine shortened the duration of the response in ducks, while increasing TI duration in guinea pigs. Physostigmine, on the other hand, increased TI duration in ducks, while shortening the response in guinea pigs. Though the neurochemical systems mediating the response may differ, it is suggested that TI could serve as a useful model behavior for studying functional homology between the brains of birds and mammals.

Baroreceptor activity has been implicated in the initiation of the immobility reflex in rabbits (Hatton, Lanthorn, Webster, & Meyer, 1978). In order to test the generality of the effect to other species, frogs, with the carotid labyrinth denervated or the glossopharyngeal nerve sectioned, were tested for the immobility reflex. The results indicate that sectioning of the glossopharyngeal nerve significantly reduced the incidence of immobility relative to controls, while frogs with the carotid labyrinth denervated were intermediate in suscept­ ibility to immobility in comparison to sectioned and control animals. The immobility reflex shares a number of common behavioral and physiological characteristics with the baroreceptor reflex. As pointed out by Gellhom (1967), increased pressure in the sino-aortic area or stimulation of the sinus nerve leads to a fall in blood pressure and heart rate, a loss in tone of striated muscle, and a tendency to sleep. In addition, spindling occurs in the cortical EEG and there is a reduced responsiveness to external stimuli. These effects are not present after denervation of the sino-aortic area. Likewise, during the immobility reflex in rabbits, there is marked hypoten­ sion of the muscles (Carli, 1969) and an initial decrease in blood pressure and heart rate, followed by a rapid increase and gradual decrease in these values over the course of the immobility episode (Carli, 1974; Hatton, Note 1); there is also a reduced responsiveness to external stimuli, and synchronization occurs in the corti­ cal EEG (Gerebtzoff, 1941; Hatton, Woodruff, & Meyer, 1975). As with the baroreceptor reflex, the incidence of occurrence of immobility is significantly reduced in rabbits following denervation of the carotid sinus or sectioning of the sinus nerve (Hatton et al., 1978). The present study was designed to examine the generality of the effect of denervation of the carotid sinus on the immobility reflex in another species.

The interactive effects of psychosocial stress and diet on the development of hypertension were investigated in spontaneously hypertensive rats. Psychosocial stress, produced through manipulation of group housing conditions, was evaluated at three levels of dietary calcium and sodium: Low (0.1% Ca2+, 0.25% Na+), Intermediate (1.0% Ca2+, 0.45% Na+), and High (2.0% Ca2+, 1.0% Na+). After 13 weeks of exposure, stressed animals had higher blood pressure and lower serum ionized calcium than nonstressed animals across all diets. Likewise, animals on the low diet had higher blood pressures and lower ionized calcium values than animals on normal or high diets regardless of stress condition. The combination of stress and low diet produced the highest blood pressure and lowest serum ionized calcium values. The results suggest that stress both independently and in combination with dietary Ca2+ altered calcium metabolism. The interaction between psychosocial stress and dietary factors appears to contribute to reductions in serum ionized calcium and elevations in blood pressure in this experimental model of genetic hypertension.