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To clarify whether exposure to 6 degrees head-down tilt (HDT) leads to alterations in body fluid volumes and responses to a saline load similar to those observed during space flight we investigated eight healthy subjects during a 4-day, 6 degrees HDT and during a time-control ambulatory period with cross-over. Compared with the ambulatory period, HDT was associated with greater urinary excretion of water and sodium (UV, U(Na)V) from 0 to 12 h (cumulated UV 1,781 +/- 154 vs. 1,383 +/- 170 ml, P < 0.05; cumulated U(Na)V 156 +/- 14 vs. 117 +/- 9 mmol, P < 0.05), and with higher plasma atrial natriuretic factor (ANF) at 4 h. Hemoglobin and hematocrit increased over the first 24 h, and blood and plasma volumes were decreased after 48 h of HDT (P < 0.05). Plasma renin activity (PRA) and aldosterone did not differ between the two groups. With prolongation of HDT, UV and U(Na)V returned close to baseline values. On the fourth HDT day, a 30-min infusion of 20 ml/kg isotonic saline was performed, while a large oral water load maintained a high urine output. The ambulatory period experiment was done with the subjects in the acute supine posture. Sodium excreted within 4 h of loading was 123 +/- 8 mmol during HDT vs. 168 +/- 16 mmol during the ambulatory period (P < 0.05). The increase in plasma ANF and decrease in PRA were greater during HDT than during the ambulatory period (ANF 30 +/- 5 vs. 13 +/- 4 pg/ml, P < 0.05; PRA -1.4 +/- 0.4 vs. -0.5 +/- 0.2 ng. ml(-1). h(-1), P < 0.05). Our data suggest that after a 3-day HDT period, thoracic volume receptor loading returns to the level seen in the upright position, leading to blunted responses to volume expansion, compared with acute supine control.

We have measured plasma volume expansion (Evans blue and hematocrit changes) and hemodynamic responses in conscious hemorrhaged and normovolemic splenectomized sheep after a 30-min infusion of either 20 ml/kg of diaspirin cross-linked hemoglobin (DCLHb), 20 ml/kg of human albumin (Alb), or 60 ml/kg of a solution of Ringer lactate (RL). All regimens expanded blood volume and increased blood pressure and cardiac output after hemorrhage. However, only 15 +/- 3% of the infused volume of RL was evident as intravascular expansion 10-min postinfusion, compared with 67 +/- 16% and 139 +/- 139% for Alb and DCLHb, respectively. DCLHb infusions were associated with higher blood pressures and lower cardiac outputs compared with RL and Alb infusions, but the increased oxygen content of blood with DCLHb resulted in systemic delivery of oxygen similar to that of the other infusions. These differences in hemodynamics and vascular volume continued for 6 h, and at 24 h vascular volume and all hemodynamics were similar in all three groups. The better volume expansion with DCLHb may be due to greater mobilization of endogenous interstitial protein or reduced transcapillary loss as total intravascular endogenous plasma protein increased after infusion of DCLHb, whereas there was an apparent loss of endogenous intravascular protein after infusions of Alb and RL. Vasoconstriction by DCLHb is one mechanism that could lower blood-to-tissue transport of fluid and protein. In addition to its oxygen-carrying capacity and vasoactivity, DCLHb is associated with volume expansion properties out of proportion to its colloid osmotic pressure.

Relatively few studies on the physiological effects of fat administration have been published. In the present study, whole body and splanchnic oxygen consumption, blood flow, blood temperature, glucose and insulin economy, and arterial and hepatic venous concentrations of hemoglobin, free fatty acids (FFA), and glycerol were measured by indirect calorimetry and catheterization technique in seven healthy men before and during 2.5 h after oral ingestion of 850 kJ of fat and in five healthy men before and during a 2.5-h intravenous (i.v.) infusion of 850 kJ of fat. Oral fat increased the splanchnic blood flow by 57 +/- 25%, reduced the plasma volume by 6 +/- 1%, reduced the arterial concentrations of FFA and glycerol by 33 +/- 7 and 50 +/- 16%, respectively, and increased arterial insulin concentration by 52 +/- 12% despite a simultaneous reduction in splanchnic insulin release, thus suggesting a reduction of the extrasplanchnic extraction of insulin. None of these effects occurred during intravenous fat infusion, and it is suggested that intestinal hormones might elicit these effects. Body heat content, unaffected after oral fat, increased by 67 +/- 20 kJ during intravenous fat infusion.

Previous studies have suggested that acute elevations of arginine vasopressin (AVP) may result in an extravascular to intravascular shift of fluid independent of any change in total body H2O (TBW). The present studies examined the chronic influence of elevated AVP on fluid volume distribution in five splenectomized, sodium-deprived conscious dogs (avg body wt = 18.9 +/- 0.7 kg). During 4 days of continuous intravenous AVP infusion (0.36 ng X kg-1 X min-1), the computerized average 24-h total body weight was maintained within 110 g of the control value by means of a sensitive servo-controlled scale device. Urine flow and urine osmolality averaged 335 +/- 52 ml/day and 637 +/- 36 mosmol/kg during the preinfusion period and changed to levels averaging 151 +/- 14 and 1,377 +/- 121 with elevated AVP (P less than 0.05). Chromium-51-labeled red cell volume (51Cr RBC), plasma volume (Evans blue), TBW (3H2O), calculated total blood volume (using 51Cr RBC and Hct), and mean arterial pressure averaged 22 +/- 1 ml/kg, 54 +/- 7 ml/kg, 0.62 +/- 0.04 l/kg, 68 +/- 3 ml/kg, and 99 +/- 3 mmHg, respectively, during the control period and remained unchanged during the AVP infusion period. Plasma protein, sodium, and osmolality averaged 6.4 +/- 0.1 g/dl, 145.7 +/- 0.8 meq/l, and 295.0 +/- 1.5 mosmol/kg during the preinfusion period and also remained unchanged with elevated AVP. We conclude from the present studies that AVP has minimal or no chronic influence on internal volume redistribution.

The effects of volume loading were examined in conscious, unrestrained, and tranquilized baboons (20-25 kg) 1-3 mo after instrumentation with miniature left ventricular pressure and diameter gauges. The response to volume loading was accompanied by significant increases (P less than 0.01) in cardiac rate (32 +/- 4 beats/min) in tranquilized baboons. When rapid saline infusion was accomplished in conscious unrestrained baboons by means of activating a remote-controlled interrogator, heart rate also rose significantly (41 +/- 8 beats/min, P less than 0.01). After cholinergic blockade with atropine, ganglionic blockade with hexamethonium, bilateral vagotomy, or combined cholinergic and beta-adrenergic blockades, volume loading failed to increase heart rate. In two smaller (12-14 kg) intact conscious baboons with relatively high spontaneous heart rates, volume loading did not alter heart rate. These experiments suggest that the Bainbridge reflex exists in larger primates with relatively low spontaneous heart rates.

We previously reported that chronic (10 days) intracerebroventricular (ivt) infusion of angiotensin II (ANG II) into conscious rabbits produced a significant rise in mean arterial pressure (MAP), water intake (WI), and urinary sodium excretion (UNaV), and a significant fall in plasma sodium (PNa) and potassium (PK) concentrations. Urinary potassium excretion (UKV) and body fluid volume were not changed significantly. In the present experiments, similar chronic infusions were carried out in intact rabbits and in rabbits with an electrolytic lesion placed in the anteroventral third cerebral ventricle (AV3V) region. Integrity of the AV3V area is essential for normal expression of a variety of acute physiological responses to ANG II injected into the brain. In rabbits with AV3V lesions, chronic ivt infusion of ANG II did not significantly alter MAP, but WI and fractional UNaV increased, and PNa decreased in a manner identical to that of sham-lesioned control rabbits. Plasma and extracellular fluid volumes increased, and body weight and food intake decreased in all rabbits during ANG II infusion, but to a slightly greater extent in the AV3V-lesioned rabbits. We conclude that an intact AV3V region is crucial for the hypertensive effect of chronic ivt fusions of ANG II in the rabbit but is not necessary for most of the fluid and electrolyte alterations associated with such infusions.

Although potassium is known to lower blood pressure in a number of forms of experimental and human hypertension, the mechanism for this effect remains unclear. We studied several possible mechanisms for this effect in the spontaneously hypertensive rat (SHR). Fourteen-week-old SHR were given 0.5% KCl in the drinking water. This potassium supplement resulted in a 16-mmHg fall in mean arterial pressure and a 22% decrease in peripheral vascular resistance. Plasma potassium increased 0.4 meq/l, while muscle potassium was unchanged. Potassium supplementation resulted in no change in plasma renin activity, plasma aldosterone, or plasma norepinephrine. Urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha was also not altered by potassium supplementation. Potassium-supplemented SHR were found to have no difference in sodium excretion compared with control SHR, and plasma volume was similar in both groups. The pressor response to angiotensin II and norepinephrine was not substantially affected by potassium supplementation. Furthermore, baroreflex control of heart rate was not altered by potassium supplementation. Finally, potassium supplementation resulted in no change in mesenteric artery angiotensin II receptor number or receptor affinity. Therefore, although potassium lowers blood pressure in the SHR by decreasing peripheral vascular resistance, the mechanism of this effect on vascular resistance remains unknown.

This study examined body fluid volumes, the pressor responses to norepinephrine (NE), and the cardiovascular responses to NE before and during infusion of an angiotensin II (ANG II) antagonist in two-kidney rabbits with unilateral renal artery stenosis (RAS) of 3 and 30 day duration. Three separate experiments were performed. In the first experiment, plasma volume, extracellular fluid volume, and total body water were measured by the distribution volumes of radioiodinated serum albumin, 35SO4, and tritiated water, respectively. No differences were seen for any of these volumes between the 3- or 30-day RAS rabbits and their controls. In the second experiment, pressor responses to infusions of several doses of NE were examined; rabbits with 3- and 30-day RAS had exaggerated pressor responses to all doses of NE when compared with the control rabbits. In the third experiment, infusion of NE at 800 ng.min-1.kg body wt-1 resulted in more pronounced increases in mean arterial pressure and total peripheral resistance (TPR) in the 3- and 30-day RAS rabbits than in the controls; after infusion of [Sar1-Ile8] ANG II the increases in mean arterial pressure and TPR during NE infusion were blunted and were of the same magnitude as in the control group. In all experiments the 30-day RAS rabbits were hypertensive, whereas the 3-day RAS rabbits were normotensive; also, plasma renin activity (PRA) values were normal in both the 3- and 30-day RAS groups. These studies demonstrated that increases in body fluid volumes are not necessary for pressor and vascular hyperresponsiveness probably is mediated by ANG II, despite normal PRA values.

To assess the effect of arginine vasopressin (AVP) and 1-deamino-8-D-AVP (DDAVP) on atrial natriuretic peptide (ANP) release, renal water and electrolyte excretion, and cardiovascular function, AVP and DDAVP were administered at a dose of 10 ng.kg-1.min-1 iv for 30 min into anesthetized dogs receiving saline infusion at a rate of 1 ml.kg-1.min-1 (n = 12). In the control study, saline was infused alone (n = 6). AVP potentiated the plasma ANP response to an increase in plasma volume produced by saline infusion, increased mean arterial blood pressure (MAP), and exaggerated the natriuresis and kaliuresis. DDAVP did not potentiate the increase in plasma ANP but enhanced the natriuresis without any rise in MAP. Saline alone increased plasma ANP as well as sodium and potassium excretion with no changes in MAP. Inulin and p-aminohippuric acid clearances did not change during these studies. The results suggest that in hydrated dogs, AVP may increase ANP release and arterial blood pressure via the vasopressor activity of AVP and potentiate the natriuresis and kaliuresis, but the increased ANP may play little role in the natriuresis.

Elevation of blood pressure induced by an acute sodium and fluid load in the anephric state has been attributed to intravascular fluid volume expansion. The present experiments were designed to study the role of vasopressin and catecholamines in this type of hypertension. Normotensive anephric rats, adrenergically intact or pretreated with alpha- and beta-adrenoceptor blockade, and deoxycorticosterone (DOC)-salt-treated anephric rats, intact or pretreated with alpha- and beta-adrenoceptor blockade, received an infusion of 2 ml containing 3 meq NaCl, followed by intravenous administration of an analogue antagonist of the vasopressor effect of arginine-vasopressin (AVP). Pressure increments induced by hypertonic saline were abolished by an AVP antagonist partly in the adrenergically intact animals (leaving a small residual pressure elevation) and completely in adrenergically blocked animals, which had a larger AVP component. Volumes expansion did not necessarily accompany increase in blood pressure after saline infusion. In fact some DOC-salt-treated animals with the highest blood pressures and norepinephrine levels exhibited contraction of plasma volume. Increments in blood pressure were negatively correlated with plasma volume changes (r = -0.687, P less than 0.05) in these animals and positively with norepinephrine levels in all adrenergically intact animals (r = 0.818, P less than 0.001). It is concluded that the hypertensive response elicited by acute hypertonic saline load is due to vasoconstriction mediated partly by vasopressin and partly by the sympathetic system, which may in some way attenuate the effect of vasopressin.

In resting supine subjects the whole-body clearance of norepinephrine (NE) based on arterial and venous sampling averaged 1.4 and 2.5 liters/min, respectively (P less than 0.02). The difference in clearance values was due to a peripheral uptake of NE averaging 45%. The calculation of plasma NE clearance based on venous sampling results in values that are too high. The plasma appearance rate of NE increased considerably after surgery, whereas the arterial blood pressure remained unchanged. This suggests that the sensitivity to NE is reduced postsurgery. Insulin has certain acute effects on cardiovascular function and plasma NE kinetics that are unrelated to the counterregulatory response to decrements in plasma glucose concentration. Insulin may both induce antagonism to the action of NE and increase the release of NE from sympathetic nerves. Intravenous insulin decreases the plasma volume and increases the hematocrit by an adrenergic mechanism. Plasma NE increases in normal subjects after an oral glucose load. This response may be of importance because in sympathectomized patients both oral glucose and insulin administration decreases the arterial blood pressure. During an oral glucose load insulin-dependent diabetics show abnormalities in the regulation of cardiovascular function and sympathetic nervous activity that may be related to the lack of rise in endogenous insulin in these patients. These results suggest that insulin may be of importance for the normal function of the cardiovascular system.

Previous research suggests that hamsters 1) fail to retain sodium after mineralocorticoid injections, 2) retain sodium after adrenalectomy equal to controls, and 3) do not develop salt appetite after mineralocorticoid or adrenalectomy. The present studies demonstrate sodium retention, body weight gain, hypernatremia, plasma volume expansion, and reduced fecal sodium excretion after daily injections of deoxycorticosterone acetate (DOCA). Salt appetite appeared after the 3rd and 4th days. Adrenalectomy caused reductions of sodium balance, plasma volume, and food intake, which were reversed by DOCA administration. Mineralocorticoids therefore represent one control of sodium metabolism in hamsters.

Plasma renin activities (PRA) and aldosterone concentrations increased in parallel over a wide range of plasma volume deficits produced in unanesthetized rats by extravascular administration of polyethylene glycol (PEG) solution. When PEG-treated rats were given water to drink, their intakes were proportional to PRA; when given water and 0.5 M NaCl, PRA and the steroid concentrations diminished concurrently in association with sodium consumption. Aldosterone concentrations and NaCl intakes were markedly enhanced after PEG treatment in rats maintained on a sodium-deficient diet for 4 days. On the other hand, a clear relation between PRA and water intake, and between circulating aldosterone levels and sodium intake, was not suggested by other experiments in this series. For example, bilateral nephrectomy abolished the rise in PRA during hypovolemia yet rats drank water normally. Moreover, aldosterone concentrations were substantially elevated by PEG treatment in the nephrectomized rats yet sodium appetite was abolished. These and other findings suggest that neither angiotensin nor aldosterone plays a prominent role in stimulating water and saline intakes during hypovolemia.

The purpose of this study was to investigate the hormonal and renal response to plasma volume expansion in the ketamine-anesthetized rhesus monkey. The blood volume was determined in nine animals and found to be 6% of the body weight. Six monkeys received isoncotic isotonic fluid amounting to 25% of the blood volume. Plasma volume expansion led to significant decrease in the plasma concentrations of antidiuretic hormone (46.7%) and aldosterone (78.4%) as well as plasma renin activity (50.0%). The mean arterial pressure, plasma osmolality, and plasma concentrations of Na+ and K+ were unaffected by plasma volume expansion. However, renal plasma flow, glomerular filtration rate, the excretion of Na+ and K+, and urine flow increased. It was concluded that, in the ketamine-anesthetized rhesus monkey, circulating hormones contribute to blood volume homeostasis presumably through a neural mechanism similar to that observed in dogs and humans.

We have investigated the mechanisms by which chemical renal medullectomy with 2-bromoethylamine hydrobromide (200 mg/kg body wt) produces hypertension in rats. Groups of chemically medullectomized rats were compared with normal rats and rats that had been partially nephrectomized to produce an equivalent fall in glomerular filtration rate. Mean arterial pressure was elevated in the medullectomized (142 +/- 6 mmHg) compared with normal rats (124 +/- 3). In the medullectomized animals this was associated with significant tachycardia (483 +/- 15 vs. 450 +/- 6 beats/min) and an increase in cardiac output (61.1 +/- 5.0 vs. 49.9 +/- 2.2 ml X min-1 X 100 g body wt-1). Plasma volume was significantly reduced in medullectomized rats (2.16 +/- 0.15 vs 3.29 +/- 0.20 ml/100 g body wt), whereas exchangeable sodium was unchanged (39.9 +/- 0.5 vs. 39.7 +/- 0.5 meq/kg body wt). By contrast, both plasma volume and exchangeable sodium were increased in partially nephrectomized rats. These results are consistent with the hypothesis that chemical medullectomy produces hypertension by increased selective sympathetic efferent activity, raising cardiac output and postcapillary venular resistance. This may be the consequence of reducing the secretion of a renomedullary humoral substance that normally inhibits such activity.

The purpose of this study was to investigate the arterial pressure response to long-term administration of beta-agonists in the chronically instrumented conscious animal model. Chronically instrumented dogs were given intravenous infusions of ritodrine (2 micrograms.kg-1.min-1) for a period of 2 wk. Several cardiovascular and renal parameters were monitored before, during, and after the ritodrine infusion, and renal function curves were constructed. After the 1st wk of infusion, a new steady state was reestablished, and this was characterized by hypotension, reduced plasma protein concentration, elevated cardiac output, expanded extracellular fluid space, and near normal levels of activity of renin-angiotensin-aldosterone systems. The renal function curve during ritodrine infusion shifted to the left with no change in slope. We propose the following: 1) the persistence of hypotension is most probably related to the resetting of the arterial pressure-kidney blood volume servocontrol mechanisms, and 2) the persistent elevation of cardiac output and reduction in peripheral resistance are most probably related to increased oxygen and nutrient demand during beta-agonist infusions.