Search

Hormones are specific molecules measured in biological fluids by elaborate analytical systems requiring meticulous attention. Variation between laboratories can be expected. However, recently published measurements of AVP, OXT, and BNP in human plasma under basal/control conditions include numbers which, between publications, vary by 100–10 000‐fold. Generally, the methods descriptions are scant, at best, and provide no information about quality control measures. Clearly, two results describing the same basal hormone concentration by numbers three orders of magnitude apart are incongruent providing reason for concern. Basal concentrations of bioactive AVP, OXT, and BNP in human plasma are in the order of 1–10 pmol/L. Therefore, assay systems applied to plasma must be able to measure concentrations of less than 1 pmol/L with appropriate specificity and accuracy. Basal concentrations of AVP, OXT, and BNP above 100 pmol/L should be reconsidered, as such results do not reflect bioactive hormone levels in humans, rats, or mice. Any concentration above 1000 pmol/L is of concern because such levels of bioactive hormone may be seen only under extreme conditions, if at all. [ABSTRACT FROM AUTHOR]

Pulmonary surfactant protein D (SP-D) is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese. However, the mechanism behind SP-D's role in energy metabolism is not known.Here we report that SP-D deficient mice had significantly higher ad libitum energy intake compared to wild-type mice and unchanged energy expenditure. This resulted in accumulation but also redistribution of fat tissue. Blood pressure was unchanged. The change in energy intake was unrelated to the basal levels of hypothalamic Pro-opiomelanocortin (POMC) and Agouti-related peptide (AgRP) gene expression. Neither short time systemic, nor intracereberoventricular SP-D treatment altered the hypothalamic signalling or body weight accumulation.In ad libitum fed animals, serum leptin, insulin, and glucose were significantly increased in mice deficient in SP-D, and indicative of insulin resistance. However, restricted diets eliminated all metabolic differences except the distribution of body fat. SP-D deficiency was further associated with elevated levels of systemic bacterial lipopolysaccharide.In conclusion, our findings suggest that lack of SP-D mediates modulation of food intake not directly involving hypothalamic regulatory pathways. The resulting accumulation of adipose tissue was associated with insulin resistance. The data suggest SP-D as a regulator of energy intake and body composition and an inhibitor of metabolic endotoxemia. SP-D may play a causal role at the crossroads of inflammation, obesity, and insulin resistance.

The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using [H.sub.2][sup.15]O as tracer. Measurements were performed at baseline, during constant intravenous infusion of nitric oxide (NO) donor glyceryl nitrate and after intravenous injection of NO synthase inhibitor [N.sup.[omega]]-monomethyl-L-arginine (L-NMMA). Using the CT image, the kidney pole areas were delineated as volumes of interest (VOI). In the data analysis, tissue layers with a thickness of one voxel were eliminated stepwise from the external surface of the VOI (voxel peeling), and the blood flow subsequently was determined in each new, reduced VOI. Blood flow in the shrinking VOIs decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 [+ or -] 0.17 ml x g [tissue.sup.-1] x [min.sup.-1] during the control period; it increased during infusion of glyceryl nitrate to 2.97 [+ or -] 0.18 ml x g [tissue.sup.-1] x [min.sup.-1] (P < 0.05) and decreased after L-NMMA injection to 1.57 [+ or -] 0.17 ml x g [tissue.sup.-1] x [min.sup.-1] (P < 0.05). Cortical blood flow was 4.67 [+ or -] 0.31 ml x g [tissue.sup.-1] x [min.sup.-1] during control, unchanged by glyceryl nitrate, and decreased after L-NMMA [3.48 [+ or -] 0.23 ml x [(g x min).sup.-1], P < 0.05]. PET/CT scanning allows identification of a renal medullary region in which the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans. blood pressure; humans; renal medulla; renal perfusion; PET/CT; L-NMMA; glyceryl nitrate

Patients with cirrhosis exhibit impaired regulation of the arterial blood pressure, reduced baroreflex sensitivity (BRS), and prolonged QT interval. In addition, a considerable number of patients have a pulmonary dysfunction with hypoxemia, impaired lung diffusing capacity ([DL.sub.co]), and presence of hepatopulmonary syndrome (HPS). BRS is reduced at exposure to chronic hypoxia such as during sojourn in high altitudes. In this study, we assessed the relation of BRS to pulmonary dysfunction and cardiovascular characteristics and the effects of hyperoxia. Forty-three patients with cirrhosis and 12 healthy matched controls underwent hemodynamic and pulmonary investigations. BRS was assessed by cross-spectral analysis of variabilities between blood pressure and heart rate time series. A 100% oxygen test was performed with the assessment of arterial oxygen tensions ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]) and alveolar-arterial oxygen gradient. Baseline BRS was significantly reduced in the cirrhotic patients compared with the controls (4.7 [+ or -] 0.8 vs. 10.3 [+ or -] 2.0 ms/mmHg; P < 0.001). The frequency-corrected QT interval was significantly prolonged in the cirrhotic patients (P < 0.05). There was no significant difference in BRS according to presence of HPS, [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII], [DL.sub.CO], or Child-Turcotte score, but BRS correlated with metabolic and hemodynamic characteristics. After 100% oxygen inhalation, BRS and the QT interval remained unchanged in the cirrhotic patients. In conclusion, BRS is significantly reduced in patients with cirrhosis compared with controls, but it is unrelated to the degree of pulmonary dysfunction and portal hypertension. Acute hyperoxia does not significantly revert the low BRS or the prolonged QT interval in cirrhosis. portal hypertension; lung function; cardiovascular regulation; hyperoxia; bioactive substances doi: 10.1152/ajpgi.00078.2010.

Saline administration may change renin-angiotensin-aldosterone system (RAAS) activity and sodium excretion at constant mean arterial pressure (MAP). We hypothesized that such responses are elicited mainly by renal sympathetic nerve activity by [[beta].sub.1]-receptors ([[beta].sub.1]-RSNA), and tested the hypothesis by studying RAAS and renal excretion during slow saline loading at constant plasma sodium concentration ([Na.sup.+] loading; 12 [micro]mol [Na.sup.+]*[kg.sup.-1]*[min.sup.-1] for 4 h). Normal subjects were studied on low-sodium intake with and without [[beta].sub.1]-adrenergic blockade by metoproM. Metoprolol per se reduced RAAS activity as expected. [Na.sup.+] loading decreased plasma renin concentration (PRC) by one-third, plasma ANG II by one-half, and plasma aldosterone by two-thirds (all P < 0.05); surprisingly, these changes were found without, as well as during, acute metoprolol administration. Concomitantly, sodium excretion increased indistinguishably with and without metoprolol (16 [+ or -] 2 to 71 [+ or -] 14 [micro]mol/min; 13 [+ or -] 2 to 55 [+ or -] 13 [micro]mol/min, respectively). [Na.sup.+] loading did not increase plasma atrial natriuretic peptide, glomerular filtration rate (GFR by [sup.51]Cr-EDTA), MAP, or cardiac output (CO by impedance cardiography), but increased central venous pressure (CVP) by ~2.0 mmHg (P < 0.05). During [Na.sup.+] loading, sodium excretion increased with CVP at an average slope of 7 [micro]mol*[min.sup.-1]*mm[Hg.sup.-1]. Concomitantly, plasma vasopressin decreased by 30-40% (P < 0.05). In conclusion, [[beta].sub.1]-adrenoceptor blockade affects neither the acute saline-mediated deactivation of RAAS nor the associated natriuretic response, and the RAAS response to modest saline loading seems independent of changes in MAP, CO, GFR, [[beta].sub.1]-mediated effects of norepinephrine, and ANP. Unexpectedly, the results do not allow assessment of the relative importance of RAAS-dependent and-independent regulation of renal sodium excretion. The results are compatible with the notion that at constant arterial pressure, a volume receptor elicited reduction in RSNA via receptors other than [[beta].sub.1]-adrenoceptors, decreases renal tubular sodium reabsorption proximal to the macula densa leading to increased NaCl concentration at the macula densa, and subsequent inhibition of renin secretion. blood pressure; angiotensin; aldosterone; natriuresis; sodium balance

Renin secretion is regulated in part by renal nerves operating through [[beta].sub.1]-receptors of the renal juxtaglomerular cells. Slow sodium loading may decrease plasma renin concentration (PRC) and cause natriuresis at constant mean arterial blood pressure (MAP) and glomerular filtration rate (GFR). We hypothesized that in this setting, renin secretion and renin-dependent sodium excretion are controlled by via the renal nerves and therefore are eliminated or reduced by blocking the action of norepinephrine on the juxtaglomerular cells with the [beta].sub.1]-receptor antagonist metoprolol. This was tested in conscious dogs by infusion of NaCl (20 [micro]mol*[kg.sup.-1]*[min.sup-1] for 180 min, NaLoad) during regular or low-sodium diet (0.03 mmol*[kg.sup.-l]*[day.sup.-1], LowNa) with and without metoprolol (2 mg/kg plus 0.9 mg*[kg.sup.-1][h.sup.-l]). Vasopressin [V.sub.2] receptors were blocked by Otsuka compound OPC31260 to facilitate clearance measurements. Body fluid volume was maintained by servocontrolled fluid infusion. Metoprolol per se did not affect MAP, heart rate, or sodium excretion significantly, but reduced PRC and ANG II by 30-40%, increased plasma atrial natrittretic peptide (ANP), and tripled potassium excretion. LowNa per se increased PRC (+53%), ANG II (+93%), and aldosterone (+660%), and shifted the vasopressin function curve to the left. NaLoad elevated plasma [Na.sup.+]] by 4.5% and vasopressin by threefold, but MAP and plasma ANP remained unchanged. NaLoad decreased PRC by ~30%, ANG II by ~40%, and aldosterone by ~60%, regardless of diet and metoprolol. The natriuretic response to NaLoad was augmented during metoprolol regardless of diet. In conclusion, PRC depended on dietary sodium and [[beta].sub.1]-adrenergic control as expected; however, the acute sodium-driven decrease in PRC at constant MAP and GFR was unaffected by [[beta].sub.1]-receptor blockade demonstrating that renin may be regulated without changes in MAP, GFR, or[[beta].sub.1]-mediated effects of norepinephrine. Low-sodium diet augments vasopressin secretion, whereas ANP secretion is reduced. blood pressure; sodium balance; angiotensin; aldosterone; vasopressin; atrial natriuretic peptide

It was hypothesized that renal sympathetic nerve activity (RSNA) and neuronal nitric oxide synthase (nNOS) are involved in the acute inhibition of renin secretion and the natriuresis following slow NaCl loading (NaLoad) and that RSNA participates in the regulation of arterial blood pressure (MABP). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages, and acutely during anesthesia. NaLoad was performed over 2 h by intravenous infusion of hypertonic solution (50 [micro]mol*[min.sup.-1]*kg body [mass.sup.-1]) at constant body volume conditions. SMTC was coinfused in amounts (20 [micro]g*[min.sup.-1]*[kg.sup-1]) reported to selectively inhibit nNOS . Directly measured MABPs of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P < 0.005). Plasma renin concentration (PRC) was reduced by renal denervation (14.5 [+ or -] 0.2 vs. 19.3 [+ or -] 1.3 mIU/l, P < 0.005) and by nNOS inhibition (12.4 [+ or -] 2.3 vs. 19.6 [+ or -] 1.6 mlU/l, P < 0.005). NaLoad reduced PRC (P < 0.05) and elevated MABP modestly (P < 0.05) and increased sodium excretion six-fold, irrespective of renal denervation and SMTC. The metabolic data demonstrated that renal denervation lowered sodium balance during the first days after denervation (P < 0.001). These data show that renal denervation decreases MABP and renin secretion. However, neither renal denervation nor nNOS inhibition affects either the renin downregulation or the natriuretic response to acute sodium loading. Acute sodium-driven renin regulation seems independent of RSNA and nNOS under the present conditions. plasma renin concentration; total body sodium; blood pressure; sodium excretion

Responses to acute sodium loading depend on the load and on the level of chronic sodium intake. To test the hypothesis that an acute step increase in total body sodium (TBS) elicits a natriuretic response, which is dependent on the chronic level of TBS, we measured the effects of a bolus of NaCl during different low-sodium diets spanning a 25-fold change in sodium intake on elements of the renin-angiotensin-aldosterone system (RAAS) and on natriuresis. To custom-made, low-sodium chow (0.003%), NaCl was added to provide four levels of intake, 0.03-0.75 mmol x [kg.sup.-1] x [day.sup.-1] for 7 days. Acute NaCl administration increased PV (+6.3-8.9%) and plasma sodium concentration (~2%) and decreased plasma protein concentration (-6.4-8.1%). Plasma ANG II and aldosterone concentrations decreased transiently. Potassium excretion increased substantially. Sodium excretion, arterial blood pressure, glomerular filtration rate, urine flow, plasma potassium, and plasma renin activity did not change. The results indicate that sodium excretion is controlled by neurohumoral mechanisms that are quite resistant to acute changes in plasma volume and colloid osmotic pressure and are not down-regulated within 2 h. With previous data, we demonstrate that RAAS variables are log-linearly related to sodium intake over a >250-fold range in sodium intake, defining dietary sodium function lines that are simple measures of the sodium sensitivity of the RAAS. The dietary function line for plasma ANG II concentration increases from theoretical zero at a daily sodium intake of 17 mmol Na/kg (intercept) with a slope of 16 pM increase per decade of decrease in dietary sodium intake. renin-angiotensin-aldosterone system; sodium intake; potassium; renin function line; dietary function line

Patients with untreated heart failure (HF) exhibit a blunted hemodynamic and neuroendocrine response to a high sodium intake, leading to excessive sodium and water retention. However, it is not known whether this is the case for patients with compensated HF receiving angiotensin-converting enzyme inhibitors and [beta]-adrenoreceptor blockers. Therefore, we determined the hemodynamic and neuroendocrine responses to 1 wk of a low-sodium diet (70 mmol/day) and 1 wk of a high-sodium diet (250 mmol/day) in 12 HF patients and 12 age-matched controls in a randomized, balanced fashion. During steady-state conditions, hemodynamic and neuroendocrine examinations were performed at rest and during bicycle exercise. In seated HF patients, high sodium intake increased body weight (1.6 [+ or -] 0.4%), plasma volume (9 [+ or -] 2%), cardiac index (14 [+ or -] 6%), and stroke volume index (21 [+ or -] 5%), whereas mean arterial pressure was unchanged. Therefore, the total peripheral resistance decreased by 10 [+ or -] 4%. Similar hemodynamic changes were observed during an incremental bicycle exercise test. Plasma concentrations of angiotensin II and norepinephrine were suppressed, whereas plasma pro-B-type natriuretic peptide remained unchanged. In conclusion, high sodium intake was tolerated without any excessive sodium and water retention in medically treated patients with compensated HF. The observation that high sodium intake improves cardiac performance, induces peripheral vasodilatation, and suppresses the release of vasoconstrictor hormones does not support the advice for HF patients to restrict dietary sodium. dietary sodium; plasma volume; exercise

Wamberg, Christian, Ronni R. Plovsing, Niels C.F. Sandgaard, and Peter Bie. Effects of different angiotensins during acute, double blockade of the renin system in conscious dogs. Am J Physiol Regul Integr Comp Physiol 285: R971-R980, 2003. First published July 17, 2003; 10.1152/ ajpregu.00262.2003.--Evidence of biological activity of fragments of ANG II is accumulating. Fragments considered being inactive degradation products might mediate actions previously attributed to ANG II. The study aimed to determine whether angiotensin fragments exert biological activity when administered in amounts equimolar to physiological doses of ANG II. Cardiovascular, endocrine, and renal effects of ANG II, ANG III, ANG IV, and ANG-(1-7) (6 pmol * [kg.sup.-1] * [min.sup.-1]) were investigated in conscious dogs during acute inhibition of angiotensin I-converting enzyme (enalaprilate) and aldosterone (canrenoate). Furthermore, ANG III was investigated by step-up infusion (30 and 150 pmol * [kg.sup.-1] * [min.sup.-1]). Arterial plasma concentrations [ANG immunoreactivity (IR)] were determined by an ANG II antibody cross-reacting with ANG III and ANG IV. Metabolic clearance rates were higher for ANG III and ANG IV (391 [+ or -] 19 and 274 [+ or -] 13 ml * [kg.sup.-1] * [min.sup.-1], respectively) than for ANG II (107 [+ or -] 13 ml * [kg.sup.-1] * [min.sup.-1]). ANG II increased ANG IR by 60 [+ or -] 7 pmol/ml, blood pressure by 30%, increased plasma aldosterone markedly (to 345 [+ or -] 72 pg/ml), and plasma vasopressin transiently, while reducing glomerular filtration rate (40 [+ or-] 2 to 33 [+ or -] 2 ml/min), sodium excretion (50 [+ or -] 7 to 16 [+ or -] 4 [micro]mol/min), and urine flow. Equimolar amounts of ANG III induced similar antinatriuresis (57 [+ or -] 8 to 19 [+ or -] 3 [micro]mol/min) and aldosterone secretion (to 268 [+ or -] 71 pg/ml) at much lower ANG IR increments (~1/7) without affecting blood pressure, vasopressin, or glomerular filtration rate. The effects of ANG III exhibited complex dose-response relations. ANG IV and ANG-(1-7) were ineffective. It is concluded that 1) plasma clearances of ANG III and ANG IV are higher than those of ANG II; 2) ANG III is more potent than ANG II in eliciting immediate sodium and potassium retention, as well as aldosterone secretion, particularly at low concentrations; and 3) the complexity of the ANG III dose-response relationships provides indirect evidence that several effector mechanisms are involved. sodium excretion; antidiuresis; blood pressure; angiotensin peptides; metabolic clearance rate

Plovsing, Ronni R., Christian Wamberg, Niels C.F. Sandgaard, Jane A. Simonsen, Niels-Henrik Holstein-Rathlou, Poul Flemming Hoilund-Carlsen, and Peter Bie. Effects of truncated angiotensins in humans after double blockade of the renin system. Am J Physiol Regul Integr Comp Physiol 285: R981-R991, 2003. First published July 17, 2003; 10.1152/ajpregu.00263.2003.--Angiotensins different from ANG II exhibit biological activities, possibly mediated via receptors other than ANG II receptors. We studied the effects of 3-h infusions of ANG III, ANG-(1-7), and ANG IV in doses equimolar to physiological amounts of ANG II (3 pmol * [kg.sup.-1] * [min.sup.-1]), in six men on low-sodium diet (30 mmol/day). The subjects were acutely pretreated with canrenoate and captopril to inhibit aldosterone actions and ANG II synthesis, respectively. ANG II infusion increased plasma angiotensin immunoreactivity to 53 [+ or -] 6 pg/ml (+490%), plasma aldosterone to 342 [+ or -] 38 pg/ml (+109%), and blood pressure by 27%. Glomerular filtration rate decreased by 16%. Concomitantly, clearance of endogenous lithium fell by 66%, and fractional proximal reabsorption of sodium increased from 77 to 92%; absolute proximal reabsorption rate of sodium remained constant. ANG II decreased sodium excretion by 70%, potassium excretion by 50%, and urine flow by 80%, whereas urine osmolality increased. ANG III also increased plasma aldosterone markedly (+45%), however, without measurable changes in angiotensin immunoreactivity, glomerular filtration rate, or renal excretion rates. During vehicle infusion, plasma renin activity decreased markedly (~700 to ~200 mIU/I); only ANG II enhanced this decrease. ANG-(1-7) and ANG IV did not change any of the measured variables persistently. It is concluded that 1) ANG III and ANG IV are cleared much faster from plasma than ANG II, 2) ANG II causes hypofiltration, urinary concentration, and sodium and potassium retention at constant plasma concentrations of vasopressin and atrial natriuretic peptide, and 3) a very small increase in the concentration of ANG III, undetectable by usual techniques, may increase aldosterone secretion substantially. healthy humans; angiotensin peptides; aldosterone secretion; sodium excretion

Angiotensin II attenuates the natriuresis of water immersion in humans. Am J Physiol Regulatory Integrative Comp Physiol 283: R187-R196, 2002. First,published March 22, 2002; 10.1152/ajpregu.00536. 2001.--The hypothesis was tested that suppression of generation of ANG II is one of the mechanisms of the water immersion (WI)-induced natriuresis in humans. In one protocol, eight healthy young males were subjected to 3 h of 1) WI (WI + placebo), 2) WI combined with ANG II infusion of 0.5 ng*[kg.sup.-1]*[min.sup.-1] (WI + ANG II-low), and 3) a seated time control (Con). In another almost identical protocol, 7-10 healthy young males were investigated to delineate the tubular site(s) of action of ANG II by the lithium clearance method ([C.sub.Li]) and were on an additional fourth study day subjected to infusion of ANG II at a rate of 1.5 ng*[kg.sup-1]*[min.sup.-1] (WI + ANG II-high). During WI + placebo, plasma concentration of ANG II decreased from 16 [+ or -] 2 to 8 [+ or -] 1 pg/ml (P < 0.05) and renal sodium excretion increased from 104 [+ or -] 15 to 294 [+ or -] 27 [micro]mol/ rain (P < 0.05). During WI + ANG II-low, plasma ANG II was not suppressed by WI, and the natriuresis was blunted by 52 [+ or -] 13% (P < 0.05). During WI + ANG II-low and WI + ANG II-high, an increase in [C.sub.Li] was prevented that was otherwise observed during WI, and fractional distal reabsorption of sodium was facilitated. In conclusion, maintaining plasma concentration of ANG II unchanged at the level of control attenuates the natriuresis of WI considerably in humans. Therefore, suppression of generation of ANG II is an important mechanism of the natriuresis of Wi in humans. Furthermore, infusion of ANG II during WI prevents an otherwise induced increase in [C.sub.Li] and facilitates the fractional distal reabsorption of sodium, probably via an effect on aldosterone release. sodium excretion; tubular function

The hypothesis that increases in plasma sodium induce natriuresis independently of changes in body fluid volume was tested in six slightly dehydrated seated subjects on controlled sodium intake (150 mmol/day). NaCl (3.85 mmol/kg) was infused intravenously over 90 min as isotonic (Iso) or as hypertonic saline (Hyper, 855 mmol/l). After Hyper, plasma sodium increased by 3% (142.0 [+ or -] 0.6 to 146.2 [+ or -] 0.5 mmol/l). During Iso a small decrease occurred (142.3 [+ or -] 0.6 to 140.3 [+ or -] 0.7 mmol/l). Iso increased estimates of plasma volume significantly more than Hyper. However, renal sodium excretion increased significantly more with Hyper (291 [+ or -] 25 vs. 199 [+ or -] 24 [micro]mol/min). This excess was not mediated by arterial pressure, which actually decreased slightly. Creatinine clearance did not change measurably. Plasma renin activity, ANG II, and aldosterone decreased very similarly in Iso and Hyper. Plasma atrial natriuretic peptide remained unchanged, whereas plasma vasopressin increased with Hyper (1.4 [+ or -] 0.4 to 3.1 [+ or -] 0.5 pg/ml) and decreased (1.3 [+ or -] 0.4 to 0.6 [+ or -] 0.1 pg/ml) after Iso. In conclusion, the natriuretic response to Hyper was 50% larger than to Iso, indicating that renal sodium excretion may be determined partly by plasma sodium concentration. The mechanism is uncertain but appears independent of changes in blood pressure, glomerular filtration rate, the renin system, and atrial natriuretic peptide. hypertonic sodium loading; osmoreceptors; renin-angiotensin-aldosterone system

The responses to A[T.sub.1]-receptor blockade (candesartan 1 mg/kg) and to concomitant volume expansion (saline 35 ml/kg for 90 min) with and without nitric oxide synthase (NOS) inhibition ([N.sup.G]-nitro-Larginine methyl ester 30 [micro]g*[kg.sup.-1]*[min.sup.-1]) were investigated in separate experiments in normal dogs. A[T.sub.1] blockade decreased arterial pressure (106 [+ or -] 4 to 96 + 5 mmHg) and increased glomerular filtration rate (GFR) by 17% and sodium excretion threefold. NOS inhibition increased arterial pressure (103 [+ or -] 3 to 116 [+ or -] 3 mmHg) and decreased GFR by 21% and reduced sodium excretion by some 80%. Volume expansion increased arterial pressure significantly in all series involving this procedure, most pronounced during combined AT1 blockade and NOS inhibition (21 [+ or -] 4 mmHg). Volume expansion during A[T.sub.1] blockade elicited marked natriuresis (26 [+ or -] 11 to 274 [+ or -] 55 [micro]mol/min) that was severely reduced by concomitant NOS inhibition (10 [+ or -] 3 to 45 [+ or -] 11 [micro]mol/min), but still much larger than that seen with volume expansion during NOS inhibition alone (2 [+ or -] 1 to 23 [+ or -] 7 [micro]mol/min). Volume expansion during A[T.sub.1] blockade increased GFR (+30%), less so during combined A[T.sub.1] blockade and NOS inhibition (+ 13%), but it did not increase GFR significantly (P = 0.07) during NOS inhibition alone. Plasma ANG II increased greater than sevenfold with A[T.sub.1] blockade and doubled with NOS inhibition (paired t-test, P < 0.05), whereas it decreased by 50-80% during volume expansion irrespective of pretreatment, i.e., during NOS inhibition, volume expansion did not generate subnormal plasma ANG II concentrations. In conclusion, 1) acute A[T.sub.1] blockade leads to hyperfiltration, natriuresis, and hyperresponsiveness to volume expansion, 2) these responses are >85% inhibitable by unspecific NOS inhibition, and 3) NOS inhibition alone is followed by increases in plasma ANG II, hypofiltration, and severe antinatriuresis that may be counterbalanced but not overwhelmed by volume expansion. Thus NOS inhibition virtually abolishes the volume expansion natriuresis, at least in part, due to the lack of appropriate inhibition of the renin-angiotensin-aldosterone system. sodium excretion; blood pressure; glomerular filtration rate; [N.sup.G]-nitro-L-arginine methyl ester; candesartan

The responses to infusion of nitric oxide synthase substrate (L-arginine 3 mg*[kg.sup.-1]*[min.sup.-1]) and to slow volume expansion (saline 35 ml/kg for 90 rain) alone and in combination were investigated in separate experiments. L-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 [+ or -] 2 beats/min), and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 [+ or -] 0.0 to 0.7 [+ or -] 0.1 ml/min). Volume expansion increased arterial blood pressure (102 [+ or -] 3 to 114 [+ or -] 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 [+ or -] 31 [micro]mol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 [+ or -] 1.7 to 1.6 [+ or -] 0.3 pg/ml). Combined volume expansion and L-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 [+ or -] 23 [micro]mol/min at plasma ANG II levels of 3.0 [+ or -] 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, L-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus L-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess. sodium excretion; free water clearance; angiotensin

The hypothesis that the carotid baroreceptor stimulation caused by a posture change from upright seated with legs horizontal (Seat) to supine (Sup) participates in the suppression of arginine vasopressin (AVP) release was investigated. Findings showed that vasopressin secretion is suppressed during an antiorthostatic posture change, which increases carotid sinus pressure, arterial pulse pressure (PP) and left arterial diameter (LAD). The suppression is absent when PP and LAD are prevented from increasing.

The effects of physiological amounts of vasopressin on the kidneys of dogs were investigated during servocontrolled overhydration to determine the contribution of various factors to natriuresis in the test subjects. The dose of vasopressin was low enough so as not to alter the mean arterial pressure and the glomerular filtration rate. Results reveal that low levels of vasopressin induce natriuresis mediated through receptors other than V2 and prostaglandin synthesis.

Research shows that the biochemical amiloride has a lithiuretic effect on the kidney nephrons of rats red on a low-sodium diet. Experiments designed to measure the fractional urinary excretion of plasma lithium in rats are described. Evidence suggests that low end-tubular sodium reabsorption is caused by low tubular sodium concentration leading to lithium uptake.

The effects of isotonic saline infusion on central venous pressure (CVP) and left atrial diameter were analyzed in healthy human males to determine the the interaction between hemodilution and natriuretic response. Analysis of CVP and LAD in human subjects after saline infusions indicated the role of saline-induced natriuresis in preventing CVP and LAD elevations. Furthermore, elevations in CVP and LAD mediate 50% of acute natriuresis caused by volume expansion which was also promoted by aldosterone release and hemodilution.

The physiological changes of mental stress were investigated by examining the effect of epinephrine (Epi) and the atrial natriuretic peptide (ANP) on forearm sympathetic activity. Subjects with mental stress had reduced forearm vascular resistance (FVR) but increased arterial Epi and forearm norEpi flow. Intra-atrial Epi infusion increased FVR, whereas intravenous Epi infusion decreased FVR, increased diastolic arterial pressure and increased heart rate. Subjects also had increased ANP. It was suggested that both Epi and ANP acted as vasodilators during mental stress.

Capillary beds in the legs respond to the changes in blood pressure caused by immersion in water by lowering the colloid osmotic pressure in the circulation. When a person is immersed partially and fully, the resultant decline in colloid osmotic pressure causes the kidneys to change its sodium excretion rate. In addition, the amount of sodium excreted by the kidneys increases as the person is immersed deeper in water.

Abstract Background Sex hormones have a pronounced effect on arginine vasopressin (AVP), and therefore on the diurnal water homeostasis. Low and high levels of plasma-estradiol as seen in the follicular phase of the menstrual cycle may therefore alter the diurnal regulation of urine production. Furthermore the structural resemblance of oxytocin to vasopressin has led to speculations about the possible antidiuretic properties of oxytocin under normal physiological conditions. To elucidate the influence of high and low p-estradiol on the regulation of the diurnal urine production, 15 normal menstruating women (21–33 y) underwent two circadian in-patient investigations, both situated in follicular phase. Methods Admitting the participants solely in the follicular phase resulted in high and low plasma-estradiol whereas plasma-progesterone was similar. Urine and blood samples were taken at predetermined time points to determine plasma AVP, plasma oxytocin, plasma aldosterone, plasma natriuretic peptide (ANP), urinary solute excretions, and urinary excretions of prostaglandin E2 (PGE-2) and aquaporin-2 (AQP-2). Blood pressure was measured every hour. Results Plasma AVP, plasma aldosterone and plasma ANP were unaffected by the different levels of estradiol. All had marked circadian variations whereas oxytocin did not display any circadian rhythm. High estradiol resulted in lower p-osmolality and p-sodium reflecting the downward resetting of the osmoreceptors. Oxytocin did not correlate with either diuresis or urine osmolality. The diurnal urine production was similar in the two groups as were urine osmolality, excretion of PGE-2 and AQP-2. AQP-2 does not have a circadian rhythm and is not significantly correlated to either AVP or oxytocin under normal physiological conditions. Conclusion High and low level of estradiol has no influence on the circadian rhythm of AVP or the subsequent urine production. High p-estradiol resets the osmoreceptors for AVP release. Furthermore it appears that oxytocin under normal physiological conditions do not contribute to the overall antidiuretic effect.

Autoregulation of cerebral blood flow (CBF) denotes that CBF is constant despite fluctuation of blood pressure within wide limits. Inhibition of the renin–angiotensin system (RAS) is known to decrease the lower and upper limits of CBF autoregulation. We have previously shown that this includes inhibition by the angiotensin receptor blocker (ARB) candesartan. In the present study we investigated the influence of the ARB candesartan on the lower limit of CBF autoregulation in two groups of Sprague-Dawley rats, on high (4.0% Na+) and low (0.004% Na+) sodium diet, respectively. Control animals were given the same diet, but no ARB. CBF was studied with the laser Doppler method. Blood pressure was lowered by controlled bleeding. Results revealed that both high and low sodium diet with low and high renin levels respectively block the influence of candesartan on CBF autoregulation. This was expected in rats on a high salt diet with a low renin level, but unexpected in rats with a low salt intake with a high renin level. [ABSTRACT FROM AUTHOR]