Alterations of vasoconstrictor and sodium-regulating hormone systems in vascularly decompensated liver cirrhosis

Plasma levels of atrial natriuretic peptide (ANP), aldosterone (PA), vasopressin (AVP), and the plasma renin activity (PRA) were examined in 15 vascularly decompensated patients suffering from liver cirrhosis, before and after administration of albumin and after a subsequent administration of furosemide. The initial ANP level was lower in 9 patients (group "A") and higher in 6 patients (group "B") than in healthy controls (Group "A": 19.5 +/- 3.0 fmol/ml; group "B": 36.7 +/- 3.9 fmol/ml; control: 25.8 +/- 2.4 fmol/ml). The initial PRA (4.4 +/- 1.0 ng AngI/ml/h) and AVP (8.5 +/- 1.5 pg/ml) activity in group "A" increased significantly compared to group "B" (PRA: 0.44 +/- 0.09; AVP: 4.1 +/- 0.5), indicating an intravascular volume depletion in group "A". Albumin infusion raised the urine and sodium excretion and the plasma concentration of ANP in group "A" but lowered in plasma levels of renin and vasopressin. The same parameters were not changed by albumin in group "B". Furosemide equally raised the urine flow rate and sodium excretion in both groups. Plasma ANP level depends on the intravascular volume, and the secondary change in its plasma concentration plays a considerable role in the retention of fluid and electrolytes in patients with cirrhosis. The increased intravascular volume in these patients depletes the fluid and electrolyte retention via the increase in ANP level.     

Effects of vasopressin and its deamino-d-arginine analogue on renin release in the isolated perfused rat kidney

The direct action of arginine-vasopressin (AVP) and its deamino-d-arginine analogue (DDAVP) on renin release (RR) has been studied in isolated rat kidneys perfused with an electrolyte solution at constant pressure in a single-pass system. AVP and DDAVP infused at various concentrations (80 to 2100 pg/ml and 80 to 8700 pg/ml, respectively) reduced volume and increased osmolality of urine in a dose-dependent way. High doses of AVP reduced renal perfusate flow and glomerular filtration rate while DDAVP had no effect on renal haemodynamics. When vasoconstrictor doses of AVP or high concentrations of DDAVP were infused, basal RR remained unchanged. However, when RR had been stimulated by infusion of isoproterenol, vasoconstrictor doses of AVP as well as high doses of DDAVP which did not increase renal vascular resistance diminished RR by about 30% (P<0.01, andP<0.05, respectively). These results suggest that the inhibition of RR by vasopressin is not related to its vasoconstrictor action.     

Effect of somatostatin on kidney function and vasoactive hormone systems in healthy subjects

Summary The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0±0.25 vs 2.4±0.2 ng AngI/ml/h;p}<0.01) and glucagon levels (40±11 vs 20±16 pg/ml;p}<0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE₂, and PGF_2alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r=0.7;p}<0.001) and urinary postaglandin E₂ and glomerular filtration (r=0.52;p}<0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.Abbreviations PAH paraaminohippuric acid - ANF atrial natriuretic factor - AVP arginine vasopressin - PRA plasma renin activity - ERPF effective renal plasma flow - GFR glomerular filtration rate - TRP tubular reabsorption of phosphate - NE norepinephrine - E epinephrine - DA dopamine - GH growth hormone     

Effects of steady-state plasma vasopressin levels on the distribution of intrarenal blood flow on electrolyte excretion.

1. In order to evaluate the effects of arginine vasopressin (AVP) on the distribution of intrarenal blood flow and on electrolyte excretion, steady-state plasma AVP levels (4-8, 19-1, 44-3, and 100-6 micro u./ml.) were produced in anaesthetized dogs, which were hydrated to minimize endogenous anti-diuretic hormone (ADH) release. 2. The urinary excretion of sodium and potassium increased without change in their filtered loads during AVP infusion. 3. Measurement by the 133xenon washout method revealed diphasic blood flow shifts, as a function of the plasma AVP level, between compartment 1 (outer cortex) and compartment 2 (inner cortex and outer medulla) without change in compartment 3 (inner medulla). 4. In a separate study, the radioactive microsphere (15 micronm) method was used with a plasma AVP levels of 19-8 micronu./ml. Blood flow (expressed as % flow/g tissue) decreased in the outer cortex and increased in the inner cortex. 5. Total renal blood flow did not change during infusion of AVP. However, the values measured by 133xenon were lower than those measured by the microsphere method. 6. There was agreement between these two independent methods that blood flow shifted from outer to inner cortex, with no change in total renal flow, at similar plasma AVP levels (19-1 and 19-8 micronu./ml.). The relationship of these intrarenal circulatory changes to the increased electrolyte excretion is discussed.     

Acute and chronic effects of vasopressin on blood pressure, electrolytes, and fluid volumes.

Physiological levels of arginine vasopressin (AVP) were continuously infused 24 h/day into six dogs for periods ranging from 7 to 34 days. The acute and chronic responses of the mean arterial pressure (MAP), body fluid volumes, renal function indices, plasma electrolyte concentrations, plasma renin activity, and urinary electrolyte and water excretion rates were measured. MAP was unaffected acutely but rose significantly to a peak on day 9 before declining toward control. MAP was significantly and positively correlated with the plasma volume, but had a diphasic correlation with the plasma sodium concentration and the change in total body sodium. The plasma sodium concentration reached a relatively stable plateau that was maintained in spite of large changes in total body water. We conclude that AVP produces only a transient hypervolemic hypertension; that AVP is a natriuretic agent, either directly or indirectly, both acutely and chronically; and that chronically it is a more potent controller of the plasma sodium concentration than of the total body water except in extreme cases.     

Plasma Renin Activity Following Central Infusion of Angiotensin II and Altered CSF Sodium Concentration in the Conscious Goat

To study central influences on the renal release of renin, angiotensin II was infused into the lateral cerebral ventricle of conscious hydrated goats. CSF sodium concentration was increased or lowered by similar infusions of hypertonic NaCl or of isotonic fructose solution. Infusion of anglotensin II in doses from 0.5 to 1 μg caused a drop in plasma renin activity (PRA) and elicited a rise in blood pressure, antidiuresis, natriuresis, and thirst. Intraventricular infusion of hypertonic NaCl also suppressed PRA, induced anti-diuresis, natriuresis, and an inconsistent rise in blood pressure. Lowering of CSF [Na⁺] by infusion of isotonic fructose caused a rise in PRA and was followed by a water diuresis in the non-hydrated animal. The fructose infusions caused some decrease in renal K⁺ excretion but no consistent change in renal Na⁺ excretion. The results indicate that angiotensin II and changes in sodium balance modulate renal renin release also via the central nervous system.     

Role of vasopressin in blood pressure regulation in conscious water-deprived dogs

The role of vasopressin in the regulation of blood pressure during water deprivation was assessed in conscious dogs with two antagonists of the vasoconstrictor activity of vasopressin. In water-replete dogs, vasopressin blockade caused no significant changes in mean arterial pressure, heart rate, plasma renin activity (PRA), or plasma corticosteroid concentration. In the same dogs following 48-h water deprivation, vasopressin blockade increased heart rate from 85 +/- 6 to 134 +/- 15 beats/min (P less than 0.0001), increased cardiac output from 2.0 +/- 0.1 to 3.1 +/- 0.1 1/min (P less than 0.005), and decreased total peripheral resistance from 46.6 +/- 3.1 to 26.9 +/- 3.1 U (P less than 0.001). Plasma renin activity increased from 12.4 +/- 2.2 to 25.9 +/- 3.4 ng ANG I X ml-1 X 3 h-1 (P less than 0.0001) and plasma corticosteroid concentration increased from 3.2 +/- 0.7 to 4.9 +/- 1.2 micrograms/dl (P less than 0.05). Mean arterial pressure did not change significantly. When the same dogs were again deprived of water and pretreated with the beta-adrenoceptor antagonist propranolol, the heart rate and PRA responses to the antagonists were attenuated and mean arterial pressure decreased from 103 +/- 2 to 91 +/- 3 mmHg (P less than 0.001). These data demonstrate that vasopressin plays an important role in blood pressure regulation during water deprivation in conscious dogs.     

Plasma concentrations of atrial natriuretic peptide, arginine vasopressin and hormones of the renin-angiotensin system in patients with end-stage renal disease

Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), plasma renin activity (PRA) and aldosterone, were measured before and after 3 h of hemodialysis in 9 patients with end-stage renal disease on maintenance hemodialysis. Hormone concentrations were also determined in the same patients on a separate occasion after 1 h of ultrafiltration (UF). Plasma concentrations of ANP were significantly higher in the patients with ESRD than in a normal reference population and declined after both 1 h and 3 h of hemodialysis. Plasma concentrations of ANP failed to exhibit a significant decline after 1 h of UF. Plasma AVP concentrations were not significantly different after either hemodialysis or UF, while plasma aldosterone concentrations fell with hemodialysis. The decline in plasma aldosterone concentrations paralleled the decrease in dialysis-induced fall in serum potassium concentrations. There was no correlation between the blood pressures, heart rate, interdialytic weight gain and estimated fluid overload and any of the hormones measured except for the plasma renin activity (PRA) which correlated significantly with the systolic blood pressure. The data suggest that ANP may not be a major factor in blood pressure regulation in normotensive patients with ESRD and its elevation in patients with ESRD is most likely due to fluid overload and atrial distention as well as a possible reduction in its metabolic clearance in renal insufficiency. The fall in plasma ANP following hemodialysis is not due to its removal by dialysis but is most likely due to a reduction in ANP production caused by dialysis-induced correction of hypervolemia.     

Gravitational stress and volume regulation.

During the past 3 decades, groundbased experiments have been performed in order to investigate the effects of increased and decreased gravitational stress, respectively, on the renal response in humans. Experiments that simulate an increase in gravitational load (+Gz) to the subjects (centrifugation, passive head-up titlt [HUT] or lower body negative pressure [LBNP] have clearly demonstrated a decrease in renal sodium and water excretion. Simultaneously, increases in plasma levels of arginine vasopressin (AVP), renin activity (PRA), aldosterone (PA), norepinephrine (NE) and decreases in ANP have been observed. Additionally, experiments that have utilized immersion of seated subjects to simulate a decreased gravitational stress (approximately 0 Gz) have demonstrated that renal water and sodium excretion increases by 100-400% and that plasma AVP, PRA, PA, and NE concentrations are reduced and ANP levels increased. Alternative experimental models conducted to simulate the effects of weightlessness in humans such as head-down tilt (HDT) and lower body positive pressure (LBPP) have yielded less consistent results than those of water immersion (WI) with respect to renal function. However, compared to a seated control HDT clearly induces an increased rate of renal fluid and sodium excretion. The demonstration that central volume expansion during WI is accompanied by an increase in renal fluid and electrolyte excretion and that central hypovolaemia during centrifugation, HUT, and LBNP is accompanied by the opposite effects indicate that changes in central blood volume is an important determinant of the renal functional changes. Results of experiments in humans during weightlessness in space are inconsistent and difficult to interpret. However, they have indicated that a cephalad redistribution of blood and fluid occurs and that this is accompanied by a decrease in total body fluid. Experimental models that, respectively, increase and decrease the gravitational stress in humans constitute promising tools in the investigation of the physiology and pathophysiology of volume regulation.     

Effects of small changes of plasma vasopressin on subcutaneous and skeletal muscle blood flow in man

The effect of vasopressin (AVP) on subcutaneous blood flow was studied by the 133Xenon wash-out method in 13 healthy subjects during three consecutive infusions of synthetic AVP, using increasing infusion rates. In seven of them, both subcutaneous and skeletal muscle blood flows were measured during the first infusion. The preinfusion, and infusion pAVP levels were 1.6 +/- 0.4, 3.4 +/- 0.4, 4.9 +/- 0.5 and 8.8 +/- 0.7 pg ml-1, respectively (mean +/- SE). The values are within the range normally found during dehydration. During the AVP infusions, the blood flow in subcutaneous tissues decreased 30-40% and the vascular resistance increased 60-80%. Neither heart rate nor blood pressure change significantly during the infusions. Plasma renin activity (PRA) decreased significantly. After cessation of the infusions, blood flow and vascular resistance rapidly returned to preinfusion values, while PRA increased very slowly. Skeletal muscle and subcutaneous tissues blood flows were found to be equally sensitive to small changes in the pAVP level. The present study has demonstrated that even minor increments of pAVP levels, as seen during dehydration, can significantly alter the regional blood flow in subcutaneous and skeletal muscle tissues in man.     

Effects of acute exercise and prolonged exercise training on blood pressure,vasopressin and plasma renin activity in spontaneously hypertensive rats

Summary The purpose of this study was to investigate the effect of swimming training on systolic blood pressure (BP_s), plasma and brain vasopressin (AVP), and plasma renin activity (PRA) in spontaneously hypertensive rats (SHR) during rest and after exercise. Resting and postexercise heart rate, as well as blood parameters such as packed cell volume (PCV), haemoglobin concentration (Hb), plasma sodium and potassium concentrations ([Na⁺], [K⁺]) osmolality and proteins were also studied. Hypophyseal AVP had reduced significantly after exercise in the SHR, whereas PRA had increased significantly in the Wistar-Kyoto (WKY) strain used as normotensive controls. Plasma AVP concentration increased in both strains. By the end of the experiment, training had reduced body mass and BP_s by only 10% and 6%, respectively. Maximal oxygen uptake was increased 10% and plasma osmolality 2% by training. The postexercise elevation of heart rate was not significantly attenuated by training. A statistically significant reduction in postexercise plasma osmolality (10%) and [Na⁺] (4%) was observed. These results suggested that swimming training reduced BPS. Plasma and brain AVP played a small role in the hypertensive process of SHR in basal conditions because changes in AVP contents did not correlate with those of BP_s. Moreover, there were no differences between SHR and WKY in plasma, hypophyseal and hypothalamic AVP content in these basal conditions. Finally, during moderate exercise a haemodilution probably occurred with an increase of plasma protein content. This was confirmed by the exercise-induced increase of plasma AVP and the reduction of hypophyseal AVP content, suggesting a release of this hormone, which probably contributed to the water retention and haemodilution. This investigation showed that swimming training produced an attenuation of the raised resting blood pressure in this strain and that plasma and brain AVP played a negligible role in the maintenance of hypertension in basal conditions. However, during training, this hormone may have played a role, training having induced simultaneously a decrease in BP_s and plasma AVP.     

Plasma epinephrine and control of plasma renin activity: possible extrarenal mechanisms.

Previous work from our laboratory has shown that physiological increments of circulating epinephrine concentration increase plasma renin activity (PRA) by an extrarenal beta-receptor mechanism. In the present experiments, epinephrine was infused intravenously at 125 ng.kg-1.min-1 for 45 min in trained, conscious dogs. PRA rose 3 to 5-fold, as previously described, and was accompanied by a transient decline of mean arterial pressure, decreased plasma potassium concentration, and increased hematocrit. Prior splenectomy to maintain hematocrit constant did not attenuate the PRA response to epinephrine. The kidneys of 4 dogs were denervated and constrictor cuff was placed around the renal artery. Renal denervation did not alter the PRA response to intravenous epinephrine infusion. A transient decline in renal perfusion pressure produced by cuff constriction only transiently increase PRA. Neither maintenance of a constant plasma potassium concentration nor oral administration of indomethacin altered the PRA response to epinephrine. We conclude that intravenous epinephrine increases PRA by a mechanism independent of the renal nerves, changes in renal perfusion pressure, hematocrit, plasma potassium concentration, and plasma prostaglandins.     

Repeated hypotension induced by nitroprusside and haemorrhage in sheep: effects on vasopressin release and recovery of arterial blood pressure

The arginine vasopressin (AVP) release in response to repeated hypotension caused by intravenous (i.v.) infusion of sodium nitroprusside (SNP) or haemorrhage was studied in conscious euhydrated sheep. Parallel determinations of renal excretion and plasma concentration of AVP were made in experiments involving two consecutive 10-min i.v. infusions of SNP (about 35 micrograms kg-1 min-1) with a 3-h interval between and repeated the next day. The AVP response to the second SNP administration was significantly reduced, but partial recovery was observed in response to the initial infusion the next day. Maximal fall in mean arterial blood pressure (MABP) and its recovery pattern did not differ in response to any of the four SNP infusions. In contrast, impaired recovery of the MABP together with markedly reduced AVP response was seen as a consequence of a hypotensive haemorrhage repeated after 3 h, but not when the interval between haemorrhages was extended to 24 h. The haemorrhage-induced increase in plasma renin activity was not affected by variations in the interval between experiments. It is concluded that the massive AVP liberation normally seen as an effect of acute isovolaemic hypotension becomes markedly reduced upon a renewed fall in the MABP occurring within 3 h. An iteration of hypotensive haemorrhage accentuates this fatigue of the hormonal response, which may contribute to the impaired recovery of the MABP.     

Effects, release and disposal of endothelin-1 in conscious dogs.

Cardiovascular and renal responses to a step-up infusion of endothelin-1 (ET-1) (1, 5, and 15 ng kg-1 min-1) were investigated in conscious dogs. In addition, the disappearance of ET-1 in arterial and central venous plasma after an infusion of 10 ng kg-1 min-1 was quantified, and the effects of vasopressin (AVP, 10 ng kg-1 min-1) and angiotensin II (AII, 2, 5, and 10 ng kg-1 min-1) on plasma ET-1 were investigated. The step-up infusion of ET-1 increased the plasma level from 3.6 +/- 0.3 to 243 +/- 23 pg ml-1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose-dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 +/- 4 to 29 +/- 3 ml min-1 and 87 +/- 16 to 71 +/- 14 mumol min-1, respectively). Decay curves for ET-1 in venous and arterial plasma were identical, and initial t1/2 was 1.1 +/- 0.1 min. Vasopressin increased arterial blood pressure (107 +/- 4 to 136 +/- 3 mmHg) beyond the infusion period and increased plasma ET-1 (85%). An equipressor dose of AII tended to decrease plasma ET-1. It is concluded that the lung is apparently not important in the removal of ET-1, that the disappearance of ET-1 follows a complex pattern, and vasopressin--in contrast to angiotensin II--is able to increase the plasma concentration of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasopressin and renin responses to hemorrhage in conscious, cardiac-denervated dogs

We measured plasma arginine vasopressin (AVP) and plasma renin activity (PRA) during continuous hemorrhage in cardiac-denervated and sham-operated conscious dogs. Hemorrhage produced comparable decreases in aortic pressure, cardiac output, stroke volume, pulmonary arterial pressure, and left and right atrial pressures in each group of dogs. After 10 ml blood/kg body wt had been removed, AVP was increased in sham-operated dogs (P less than 0.05) but not in cardiac-denervated dogs. After 20 and 30 ml blood/kg body wt had been removed, AVP was increased in all dogs, but the response was markedly attenuated in cardiac-denervated dogs. Hemorrhage at 10 and 20 ml/kg caused comparable increases in PRA in each group of dogs. However, at 30 ml/kg hemorrhage the increase in PRA was significantly higher in cardiac-denervated dogs than in sham-operated dogs. Our results suggest that cardiac receptors play a dominant role in mediating the release of AVP during hemorrhage in conscious dogs. In contrast, we found no evidence for a dominant role of cardiac receptors in mediating renin secretion during hemorrhage.     

Calciuresis elicited by spontaneous rehydration in dehydrated sheep

Cardiovascular and renal responses to a step-up infusion of endothelin-1 (ET-1) (1, 5, and 15 ng kg^-1 min^-1) were investigated in conscious dogs. In addition, the disappearance of ET-l in arterial and central venous plasma after an infusion of 10 ng kg^-1 min^-1 was quantified, and the effects of vasopressin (AVP, 10 ng kg^-1 min^-1) and angiotensin II (AII, 2, 5, and 10 ng kg^-1 min^-1) on plasma ET-1 were investigated. The step-up infusion of ET-1 increased the plasma level from 3.6 ± 0.3 to 243 ± 23 pg ml^-1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose-dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 ± 4 to 29 ± 3 ml min^-1 and 87 ± 16 to 71 ± 14 μmol min^-1, respectively). Decay curves for ET-1 in venous and arterial plasma were identical, and initial t_½ was 1.1 ± 0.1 min. Vasopressin increased arterial blood pressure (107 ± 4 to 136 ± 3 mmHg) beyond the infusion period and increased plasma ET-1 (85%). An equipressor dose of AII tended to decrease plasma ET-1. It is concluded that the lung is apparently not important in the removal of ET-1, that the disappearance of ET-1 follows a complex pattern, and vasopressin – in contrast to angiotensin II – is able to increase the plasma concentration of ET-1. The latter may suggest that ET-1 is involved in the prolonged pressor action of AVP observed.     

Effects of intraruminal loads of saline or water followed by voluntary drinking in the dehydrated lactating goat

In five goats water deprivation for 26 h increased plasma osmolality, total plasma protein concentration, and plasma vasopressin (AVP) concentration to higher levels during lactation compared to nonlactation. At the end of the dehydration period intraruminal loads of saline or water (corresponding to 50% of the body weight loss) were given to lactating goats. The saline load decreased the plasma protein concentration below control levels, while plasma osmolality, Na concentration and AVP did not change. After the water load the plasma protein concentration stayed elevated. Plasma osmolality, Na concentration and AVP fell, but remained significantly above control levels. Both plasma renin activity (PRA) and aldosterone (PA) concentration increased after water, but decreased after saline administration. Three hours after the fluid loads the goats were offered water to drink. AVP decreased at the sight of water. After drinking, plasma osmolality, Na and AVP continued to decrease in water loaded animals, and fell also in saline loaded goats. PRA remained elevated, and PA increased in water loaded goats, while these hormones still were depressed in saline loaded goats. Mean renal 'free water clearance' became positive after drinking in both groups. It is concluded that the water losses with the milk cause lactating goats to become dehydrated more rapidly than non-lactating goats during water deprivation. Lowering of the plasma osmolality and Na concentration are more important than restoration of the plasma volume in suppressing the high plasma AVP concentration in the dehydrated lactating goat. The water diuresis, which occurred after voluntary drinking, indicates that the goats had not been able to anticipate their water deficit accurately.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of the actions of angiotensin on the central nervous system of conscious dogs

Angiotensin II (ANG II) acts on the brain to elevate blood pressure (BP), stimulate drinking, increase the secretion of vasopressin and corticotropin (ACTH), and inhibit the secretion of renin. The present studies were designed to evaluate the possible physiological significance of these effects. The experiments were performed in conscious dogs with small catheters chronically implanted in both carotid and both vertebral arteries. ANG II was infused into both carotid or both vertebral arteries in doses of 0.1, 0.33, 1.0, and 2.5 ng.kg-1.min-1. Intravertebral ANG II produced dose-related increases in BP that were generally accompanied by increases in heart rate. Intracarotid angiotensin also increased BP but did not change heart rate. Intracarotid ANG II stimulated drinking and, at the highest dose only, increased the secretion of vasopressin, ACTH, and corticosteroids. Intravertebral and intracarotid ANG II suppressed plasma renin activity (PRA). In a parallel series of experiments, the effects of intravenous ANG II, in doses of 2, 5, 10, and 20 ng.kg-1.min-1, were studied. These infusions produced dose-related increases in BP and water intake and suppressed PRA. Only the highest dose of ANG II increased vasopressin or corticosteroid secretion. Analysis of these results in terms of calculated or measured changes in plasma ANG II concentration indicate that the central cardiovascular and dipsogenic actions of angiotensin, as well as the suppression of PRA, can be elicited by concentrations of the peptide that are within the physiological range. On the other hand high, probably supraphysiological, levels of ANG II are required to increase vasopressin or ACTH secretion.     

Increase in plasma sodium enhances natriuresis in response to a sodium load unable to change plasma atrial peptide concentration

The influence of plasma sodium concentration in the control of sodium excretion was investigated in conscious, water-diuretic dogs. NaCl was infused for 60 min as a hypertonic or isotonic solution at a rate of 60 mumol NaCl min-1 kg-1 body wt. Plasma sodium concentration rose only during hypertonic infusion (P less than 0.05). Sodium excretion increased markedly with both infusions (hypertonic, from 2.4 +/- 0.6 to 105 +/- 27 mumol min-1; isotonic, from 3.9 +/- 1.3 to 58 +/- 17 mumol min-1). Fractional sodium excretion increased more during hypertonic than during isotonic infusion. Hypertonic infusion decreased diuresis from 3.1 +/- 0.5 to 1.3 +/- 0.6 ml min-1, while isotonic infusion elicited an increase from 3.9 +/- 0.5 to 7.2 +/- 0.7 ml min-1. Plasma renin activity and plasma aldosterone decreased markedly in both series (P less than 0.05), the relative changes in the two series being very similar. Central venous pressure increased (2.8 +/- 0.7 to 4.5 +/- 1.0 mmHg) during isotonic infusion but not significantly during hypertonic infusion. Arterial pressure, heart rate and plasma levels of atrial natriuretic peptide and catecholamines did not change measurably in either series. It is concluded that simultaneous increases in extracellular volume and sodium concentration cause a larger natriuretic response than a change in volume alone, and that a 40-fold increase in sodium excretion may occur without measurable changes in plasma atrial natriuretic peptide concentration.     

Renal response to captopril in conscious dogs pretreated with indomethacin

This study was designed to determine whether the prostaglandins mediate the renal effects of captopril in the conscious sodium-replete dog. In a group of control animals (n = 9), effective renal plasma flow (ERPF) increased from 185 +/- 15 to 230 +/- 12 ml/min and plasma renin activity (PRA) increased from 0.64 +/- 0.15 to 12.9 +/- 1.1 ng ANG I . ml-1 . h-1 after captopril (10 mg/kg bolus plus 10 micrograms . kg-1 . min-1 i.v.) administration. Glomerular filtration rate (GRF) and sodium excretion (UnaV) were also increased significantly following captopril treatment, whereas urine volume (V), potassium excretion (UkV), mean arterial pressure (MAP), and heart rate (HR) remained unchanged throughout the experiment. When the same dose of captopril was given to indomethacin-pretreated dogs (5 mg/kg bolus plus 2 micrograms . kg-1 . min-1 i.v.), ERPF increased from 170 +/- 8 to 265 +/- 18 ml/min and PRA increased from 1.2 +/- 0.4 to 14.6 +/- 3.0 ng ANG I . ml-1 . h-1 after the captopril, while UnaV, UkV, and V remained unchanged. These data demonstrate that the prostaglandins do not mediate the ability of captopril to increase PRA or effective renal plasma flow in this experimental model.