Cardiorenal reflexes do not attenuate the renal effects of infused atriopeptin in conscious dogs.

Low-dose infusions of atriopeptin produce only a modest diuresis and natriuresis. However, these infusions also decrease atrial pressures, a change that has been postulated to elicit an antidiuretic and antinatriuretic reflex from cardiac receptors and thereby to attenuate the direct renal effects of atriopeptin. To determine whether the renal effects of intravenously administered atriopeptin might be attenuated by a cardiorenal reflex, we infused alpha-human atrial natriuretic peptide (alpha-hANP) into cardiac-denervated and sham-operated (normal) conscious dogs. Following a control period, alpha-hANP was infused into each dog at 12.5, 25, or 50 ng.kg-1.min-1 for 1 hr. Infusion of alpha-hANP at 50 ng.kg-1.min-1 produced similar decreases in left atrial pressure in both normal and cardiac-denervated dogs (peak changes, -1.6 +/- 0.8 vs -2.4 +/- 0.9 mm Hg, respectively). Increases in urine flow (peak changes, 0.13 +/- 0.05 vs 0.20 +/- 0.06 ml/min) and sodium excretion (peak changes, 56 +/- 22 vs 70 +/- 11 microEq/min) also were not different between groups. The lower doses of alpha-hANP also elicited renal and hemodynamic responses in the cardiac-denervated dogs that did not differ significantly from those in the normal dogs. These data indicate that the diuresis and natriuresis elicited by intravenously administered alpha-hANP are not attenuated by a cardiorenal reflex in conscious dogs.     

Atriopeptin alters the vasopressin and renin responses elicited by hemorrhage

This study was designed to investigate whether an infusion of atrial peptide is capable of modulating the hormonal and hemodynamic responses elicited by acute hemorrhage. Conscious dogs were bled at a rate of 0.8 ml.kg-1.min-1 until 20 ml of blood/kg body wt had been removed. Two experiments were performed on each dog; in one experiment the animal was given alpha-human atrial natriuretic peptide (alpha-hANP) (50 ng.kg-1.min-1) dissolved in saline; in the other only the saline vehicle was given. Right and left atrial pressures decreased during hemorrhage in all experiments; the absolute decreases were greater when the animals received atriopeptin, but the differences between treatments were statistically significant only for right atrial pressure. Cardiac output decreased (P less than 0.05) and total peripheral resistance increased (P less than 0.05) during hemorrhage when atriopeptin was infused; although these variables showed similar trends when vehicle alone was infused during hemorrhage, no significant changes occurred. Infusion of atrial peptide did not affect the decrease in arterial blood pressure that occurred during hemorrhage. The increase in plasma vasopressin induced by hemorrhage was potentiated, but the increase in plasma renin activity was attenuated when alpha-hANP was infused. Hemorrhage increased circulating aldosterone levels in each experiment, but the response was less pronounced when alpha-hANP was given during the experiment. Intravenous administration of alpha-hANP modulates the hemodynamic responses elicited by hemorrhage, potentiates the rise in plasma vasopressin, and attenuates the rise in plasma renin activity induced by acute blood loss in conscious dogs.     

Modification of the renal response to endopeptidase inhibition and atrial natriuretic peptide infusion in normal dogs.

Inhibition of intrarenal neutral endopeptidase 24:11 (NEP) increases the natriuretic response to infused atrial natriuretic peptide (ANP). In various models of canine heart failure, angiotensin and kinins have been shown to modulate ANP and (or) NEP activity. In the present study, we examined possible modulators of NEP activity in normal dogs by infusing various agents into the left renal artery (or by denervating the left kidney) and comparing the response of this kidney with that of the contralateral one following the combined intravenous infusion of Squibb 28603 (a potent NEP inhibitor) and ANP (75 ng.kg-1.min-1). Four dogs received angiotensin (1.5 ng.kg-1.min-1) into the left renal artery, 8 dogs received saralasin (5 micrograms/min), 5 dogs received noradrenaline (2 micrograms/min), and 6 dogs received bradykinin (3 micrograms/min). Five dogs underwent left renal denervation. Angiotensin inhibited sodium excretion following the NEP inhibitor alone and after the NEP inhibitor plus ANP. Saralasin augmented the natriuretic response. None of the other protocols influenced sodium excretion. We conclude that angiotensin may modulate either the enzymatic degradation of ANP or influence its renal tubular effects.     

Physiological responses to low dose infusions of atrial peptide in conscious dogs

Mongrel dogs prepared with chronic catheters in their femoral artery and vein and urinary bladder received 60 minute infusions of atrial peptide ranging from 5 to 100 ng/kg/min. Infusion of atrial peptides caused dose dependent increases in plasma atrial peptide concentration with doses of 25 ng/kg/min or less increasing plasma concentrations to levels observed in normal animals during stimulation of endogenous atrial peptide secretion. Atrial peptide infusion at doses of 10 ng/kg/min and above caused significant decreases in mean arterial pressure which were not accompanied by statistically significant changes in heart rate. Atrial peptide infusion at doses of 25 ng/kg/min and above increased urinary sodium excretion and urine flow rate. Atrial peptide infusion was without effect on plasma vasopressin, ACTH and corticosterone concentrations. However, atrial peptide infusion resulted in dose dependent decreases in plasma aldosterone concentration and plasma renin activity, but the decreases were only significant with the high physiologic (25 ng/kg/min) and pharmacologic doses (50 & 100 ng/kg/min). These data show that atrial peptide infusions in conscious dogs have minimal effects when infused in small doses that mimic endogenous atrial peptide release. At higher doses, significant effects on the cardiovascular, renal and endocrine systems can be observed but their physiological significance is unclear.     

Acute effects of angiotensin II in intact and adrenalectomized conscious dogs

Renal effects of A II, retention of sodium and water, may be mediated by the stimulation of aldosterone secretion and/or by direct effects of A II on the kidneys. An attempt was made to differentiate between these two possibilities. Methods: Conscious, female beagle dogs were used. The dogs were kept under standardized conditions (metabolic cage, daily sodium intake 4.5 mmol X kg-1 bw, chronically implanted arterial and venous catheters, i.v. hormone substitution after adrenalectomy by a portable pump). A II was infused i.v. over a period of 60 min after 60 min control. (Rate: 1, 4, 20 or 200 ng X min-1 X kg-1 bw). Results: Mean arterial blood pressure (MABP) increased with 20 and 200 ng A II X min-1 X kg-1 bw by an average of 34 mm Hg and 65 mm Hg resp. before and after adrenalectomy. Before adrenalectomy: sodium and water excretion decreased always at 4 and 20 ng A II X min-1 X kg-1 bw, whereas a rate of 200 ng A II X min-1 X kg-1 bw had different effects on renal sodium and water excretion. After adrenalectomy: sodium and water excretion decreased at 4 ng A II X min-1 X kg-1 bw. Whereas a rate of 20 and 200 ng. -As no marked alterations of the glomerular filtration rate occurred, sodium retention observed was mainly due to tubular effects of A II. Plasma aldosterone concentration increased at 4, 20 and 200 ng A II X min-1 X kg-1 bw in the intact dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary vascular responses to angiotensin II and captopril in conscious dogs

Our objectives were to investigate the extent to which angiotensin II (ANG II) and converting-enzyme inhibition (CEI) exert a direct vasoactive influence on the pulmonary circulation of conscious dogs. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q. The effects of ANG II infusion (60 ng X kg-1 X min-1, iv) and CEI with captopril (1 mg/kg plus 1 mg X kg-1 X h-1, iv) on pulmonary vascular P/Q plots were assessed first with the conscious dogs intact and again after combined administration of pharmacological antagonists to block sympathetic alpha- and beta-adrenergic, cholinergic, and arginine vasopressin receptors. In intact dogs, ANG II increased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure, PAP-PCWP) over the entire range of Q studied (60-120 ml X min-1 X kg-1). Conversely, CEI decreased (P less than 0.05) PAP-PCWP at each level of Q. After administration of the autonomic nervous system and arginine vasopressin receptor antagonists, ANG II again increased (P less than 0.01) and CEI decreased (P less than 0.01) PAP-PCWP over the entire range of Q studied. Thus exogenous administration of ANG II results in active, nonflow-dependent constriction of the pulmonary circulation, and this effect is not dependent on the autonomic nervous system or increased circulating levels of arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic factor release during acute infusion of isoproterenol in the conscious rat.

The effect of beta-adrenergic stimulation on atrial natriuretic factor (ANF) release was studied in conscious rats. 20-min infusion of 85 or 850 ng kg-1 min-1 isoproterenol (ISO) resulted in positive inotropic and chronotropic responses and no elevation of atrial pressures. A slight increase in plasma ANF, together with a drop in blood pressure, were observed only in the group infused with the higher dose. During the infusion of 850 ng kg-1 min-1 ISO, there was no relationship between plasma ANF and any of the haemodynamic parameters, with the exception of mean arterial pressure (r = 0.72, P less than 0.05, n = 9). Larger doses (greater than 3 micrograms kg-1 min-1) were toxic. We conclude that beta-adrenergic stimulation is not an important stimulus for ANF release when diastolic resting tension is low.     

Cardiovascular and renal effects of calcitonin gene-related peptide in hypertensive dogs

The systemic cardiovascular and renal effects of synthetic beta-human calcitonin gene-related peptide (beta-hCGRP) were examined in conscious normotensive and one-kidney one-clip (1K-1C) hypertensive dogs. beta-hCGRP was infused intravenously at 10 and 50 ng/kg/min for 75-min periods each. Mean arterial pressure did not change significantly (p greater than 0.05) in either group during low dose infusion of beta-hCGRP, but infusion of beta-hCGRP at 50 ng/kg/min produced a fall in mean arterial pressure from 140 +/- 4 to 116 +/- 6 mmHg (p less than 0.05) in the hypertensive dogs (n = 4) and from 100 +/- 4 to 78 +/- 3 mmHg (p less than 0.05) in the normotensive dogs (n = 4). Heart rates increased significantly during infusion of beta-hCGRP in both groups. Also, renal sodium and potassium excretion decreased (p less than 0.05) in the two groups at both the low and high doses of beta-hCGRP. Creatinine clearance was unchanged in normal dogs and decreased (p less than 0.05) in 1K-1C hypertensive dogs at the high rate of beta-hCGRP infusion. The clearance of p-aminohippurate increased approximately 20% (p less than 0.05) in both groups with the low dose infusion of beta-hCGRP but further increases were elicited only in the normotensive dogs in response to the elevation in the beta-hCGRP infusion rate. Plasma renin and aldosterone levels increased (p less than 0.05) above control levels during the maximum hypotensive response to beta-hCGRP infusion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of sodium and water excretion in the antihypertensive effect of vasopressin in the spontaneously hypertensive rat.

Mean arterial pressure (mmHg (1 mmHg = 133.322 Pa)), sodium excretion rate (mumol.kg-1.min-1), and urine flow (microL.kg-1.min-1) were measured in conscious unrestrained spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before, during, and after a 3-h intravenous infusion of arginine vasopressin (20 ng.kg-1.min-1), an equipressor dose of phenylephrine, or an infusion of the vehicle. Cessation of the phenylephrine infusion was associated with a return of arterial pressure to preinfusion control values in both SHR and WKY. Cessation of the vasopressin infusion was also associated with a return of arterial pressure to preinfusion values in WKY. In contrast, in the SHR, arterial pressure fell from a preinfusion control level of 164 +/- 6.2 to 137 +/- 4 mmHg within 1 h of stopping the vasopressin infusion. Five hours after stopping the infusion, pressure was 134 +/- 3 mmHg (29 +/- 5 mmHg below preinfusion levels). Similar to the WKY, cessation of a vasopressin infusion was associated with a return of arterial pressure to preinfusion values in Sprague-Dawley rats. Thus, the failure to observe a hypotensive response in normotensive rats was not a peculiarity of the WKY strain. Sodium excretion rates increased during the infusions of vasopressin to a greater extent in SHR than in WKY. However, the natriuresis induced by phenylephrine was not significantly different from that generated by vasopressin in SHR, and in WKY, the natriuresis was greater for phenylephrine than for vasopressin. Urine output increased to a greater extent during the infusions of phenylephrine in both SHR and WKY than during vasopressin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central effects of atrial natriuretic peptide on plasma catecholamines, vasopressin, renin and beta-endorphin and on renal excretory functions in the dog

Atrial natriuretic peptide (ANP) has been identified in the central nervous system and its participation in regulation of various regulatory brain functions has been postulated. To elucidate whether central ANP influences endocrine systems related to blood pressure regulation and renal excretory functions, effects of infusion of ANP at a rate of 120 ng.min-1 into the third cerebral ventricle on plasma level of epinephrine (E), norepinephrine (NE), renin, vasopressin and beta-endorphin as well as on excretion of urine, sodium, potassium (UKV) solutes and free water (CH2O) were investigated in conscious dogs. Significant decrease of plasma E from 77.6 +/- 7.0 to 62.1 +/- 4.8 pg.ml-1 and of NE from 345.5 +/- 20.7 to 286.4 +/- 15.0 pg.ml-1 was found at the end of 30 min lasting ANP infusion. Significant elevation of PRA and UKV and a decrease in CH2O were found 60 min after ANP infusion. No significant changes in other variables were found. In time control experiments plasma hormones concentration and renal excretory functions were not significantly influenced. The results suggest that central ANP may affect the sympatho-adrenal outflow.     

Does adenosine modulate the natriuretic response to ANP in normal dogs?

To determine if the usual natriuretic response to ANP could be altered by raising intrarenal levels of adenosine, ANP was administered to normal anesthetized dogs at 100 ng.kg-1.min-1 i.v. before and after the administration of adenosine (3 micrograms.kg-1.min-1) into the left renal artery (n = 8). For each kidney, the group mean delta UNaV in response to ANP was unchanged by the presence of adenosine. However, following intrarenal infusion of adenosine, this unaltered average response for the infused kidney was achieved by either attenuation or exaggeration of the natriuresis to ANP in half the dogs, respectively. When intrarenal levels of extracellular adenosine were elevated by the i.v. infusion of dipyridamole in seven dogs, there was uniform exaggeration of an ANP-induced natriuresis by an average of 145 mu equiv./min. The provision of theophylline by itself (an adenosine antagonist) had no effect on UNaV but prevented the dipyridamole-induced exaggerated natriuresis to ANP. The infusion of adenosine deaminase into one renal artery reduced the natriuretic response to ANP. We conclude that elevated intrarenal levels of adenosine will exaggerate an ANP-induced natriuresis possibly by altering intracytosolic Ca2+.     

Prostaglandin E1 increases myocardial contractility in the conscious dog

The systemic and inotropic properties of prostaglandin E1 (PGE1) were investigated in 20 unanesthetized dogs. Pairs of ultrasonic dimension gauges and a micromanometer were implanted in the subendocardium and the apex of the left ventricle (LV), respectively. Seven to ten days later, increasing doses of PGE1 were infused into the left atrium. To appreciate the inotropic effects of the agent, the heart rate was maintained constant at 150 beats/min in a subgroup of dogs while preload was modified by bleeding or saline infusion over matched ranges of end-diastolic segmental length (EDL) during placebo and PGE1 infusions (0.25 microgram . kg-1 . min-1). LV function curves (delta L: systolic segmental shortening versus EDL) were plotted. Increasing doses of PGE1 above 0.031 microgram . kg-1 . min-1 brought a progressive decrease of left ventricular end-diastolic pressure, EDL, delta L, and peak left ventricular systolic pressure. The heart rate increased significantly at dosages from 0.063 to 0.125 microgram . kg-1 . min-1, and peak positive dP/dt after an initial increase fell at the dose of 0.5 microgram . kg-1 . min-1. The LV function curves invariably showed a shift to the left when PGE1 was administered; as the basal EDL was restored during PGE1 infusion, delta L reached a 33% increase (p less than 0.001). Thus, in addition to its potent vasodilating properties that are more prominent on preload than afterload, PGE1 increases myocardial contractility in the conscious dog.     

Effect of vasopressin and V1 receptors blockade on hypotensive action of ANP in normotensive (WKY) and spontaneously hypertensive rats.

The aim of the study was to find out whether vasopressin (AVP) modifies hypotensive and heart rate accelerating effects of atrial natriuretic peptide (ANP) in normotensive (WKY) and spontaneously hypertensive (SHR) conscious rats. The effect of i.v. administration of 1; 2 and 4 micrograms of ANP on blood pressure (MP) and heart rate (HR) was compared during i.v. infusion of 0.9% NaCl (NaCl), NaCl+AVP (1.2 ng kg-1 min-1) and NaCl+dEt2AVP (V1 receptors antagonist, 0.5 microgram kg-1 min-1). AVP increased MP in SHR and WKY and decreased HR in SHR. V1 antagonist decreased MP and increased HR only in SHR. In SHR ANP decreased MP and increased HR during NaCl, AVP and V1 antagonist infusion. In WKY these effects were observed only during AVP administration. In each experimental situation hypotension and tachycardia induced by ANP were greater in SHR than in WKY. In both strains ANP induced changes in MP and HR were enhanced during AVP in comparison to NaCl infusion. V1 antagonist did not modify effects of ANP in WKY and SHR. The results indicate that ANP abolishes hypertensive response induced by blood AVP elevation and that the basal levels of endogenous vasopressin acting through V1 receptors does not interfere with hypotensive action of ANP neither in WKY nor in SHR.     

The effect of Ringer solution induced extracellular volume expansion on kidney function

The present study quantitated the effects of extracellular volume expansion on sodium and water excretion in 118 anesthetized dogs. The animals received a priming injection of 10 ml kg-1 Ringer solution i.v. which was followed by a constant Ringer solution infusion at a rate of 0.25 ml.min-1.kg-1 until the end of the experiment. Fifteen minutes after the start of the constant infusion the renal parameters were examined in 11 subsequent 15 min periods (the total time was 3 hours). Volume expansion produced no significant change in arterial blood pressure, glomerular filtration rate (GFR), plasma sodium and potassium concentration or, haematocrit, but did reduce the CPAH from 284 ml.min-1 to 218 ml.min-1 (the data were calculated for 100 gram wet kidney weight). There were constant significant increases in the urinary excretion rate from 0.84 ml.min-1 to 4.06 ml.min-1 and the 39% of the infused water was excreted during the experiment. Volume expansion also caused a significant increase in sodium excretion during the three first periods from 120 mumol.min-1 to 329 mumol.min-1 followed by a small but significant decrease. The sodium excretion at the end of the experiment was 221 mumol.min-1 and the 23% of the infused sodium was excreted in the course of the experiment. The increase of the water excretion during the volume expansion was associated with fall of the urine osmolality and the urine because hypoosmotic as compared to the plasma. We have provided evidence that vasopressin was not involved in the control of water excretion in our experiments. It is concluded that neither filtered sodium nor decreased aldosterone secretion can account for the increase in sodium excretion that occurs after Ringer solution loading in the dog. It has been proposed that a decrease in plasma protein concentration may decrease passive sodium reabsorption due to oncotic forces in the proximal tubule. The Ringer solution diuresis elicits a rise in medullary blood flow, thereby causing a washout of medullary sodium. This might dissipate the osmotic force for the back-diffusion of water from the collecting duct. Our studies indicate that the response of the diluting segments of the distal nephron to increased delivery of sodium depends upon the presence or absence of volume expansion. However the increase of the distal tubular loading activates the tubuloglomerular feedback which increases the proximal tubular reabsorption. Based on these assumptions our studies provide further evidence that the tubuloglomerular feedback regulates the blood pressure in the peritubular capillaries in the cortex around the proximal tubules.     

Inhibition by angiotensin II of some vasopressin effects on renal function in sheep.

The effects of intravenous infusions of arginine vasopressin (AVP) alone and with angiotensin II (AII) on renal function were studied in conscious Merino ewes. AVP at 11.5 pmol.min-1 caused an increase in water and electrolyte output which was associated with a rise in glomerular filtration rate (GFR), solute clearance, solute-free water reabsorption and tubular sodium reabsorption. Addition of AII of 100 ng.min-1 generally reversed all of these effects. The filtration fraction, which rose during AVP infusion, increased further when AII was added due to a greater fall in renal plasma flow than in GFR. The diuretic and electrolyte-excreting effects of infused AVP appeared to be brought about by an increase in GFR. It is suggested that this inappropriate effect of AVP, which is secreted in response to water deprivation, could be countered by the simultaneous production of AII.     

Biological effects of a proglumide derivative as cholecystokinin antagonist in conscious dogs

In conscious dogs we studied the effects of a new cholecystokinin (CCK) antagonist (coded CR 1505) on CCK8-stimulated exocrine pancreatic secretion and release of pancreatic polypeptide (PP). Graded doses of CCK8 (25-400 ng kg-1h-1) were infused i.v. Experiments were repeated against a background infusion of CR 1505 at different doses (0.1, 1 and 10 mg kg-1h-1). The lowest dose of CR 1505 had no biological effects. However, at the upper two doses the compound significantly inhibited the CCK8-stimulated PP release. Furthermore, a significant inhibition of exocrine pancreatic protein secretion was observed with 10 mg kg-1h-1 of CR 1505 (P less than 0.05). The results suggest that CR 1505 could be a useful tool in defining the physiological role of CCK in vivo.     

Effect of intravenous epinephrine infusion on plasma renin activity in adrenalectomized dogs

Previous experiments have shown that circulating epinephrine stimulates renin secretin and increases plasma renin activity (PRA) when it is infused intravenously, but not when it is infused directly into the renal artery at similar infusion rates. The present experiments were designed to test the hypothesis that the adrenal glands mediate the PRA response to intravenous epinephrine infusion. Accordingly, anesthetized dogs were prepared with either an acute bilateral adrenalectomy or a sham-adrenalectomy procedure. Epinephrine was then infused intravenously into each animal for 45 minutes at a rate of 25 ng X kg-1 X min-1. Time control experiments in which epinephrine was not infused were also conducted. In sham-adrenalectomized dogs, PRA (in nanograms per ml h-1) rose from 4.1 +/- 1.4 in the control period to 13.0 +/- 3.0 during intravenous epinephrine infusion (means +/- SE; p less than 0.01). In adrenalectomized dogs, PRA rose from 2.1 +/- 0.4 during the control period to 5.5 +/- 0.9 during intravenous epinephrine infusion (p less than 0.01). Neither the absolute increments in PRA nor the percent increases in PRA were significantly different between the two groups receiving epinephrine. PRA remained unchanged in time control experiments. These data demonstrate that the adrenal glands need not be present in order for intravenous epinephrine infusion to elicit an increase in PRA. The data do not support the hypothesis, therefore, that epinephrine-induced increases in PRA are initiated by receptors located within the adrenal glands.     

Antagonistic effects of naloxone on CCK-octapeptide induced satiety and rumino-reticular hypomotility in sheep

Continuous intracerebroventricular (ICV) infusion of CCK-octapeptide (CCK8) was performed in ewes fitted with a permanent cannula into the lateral cerebral ventricle and Nichrome electrodes on the reticulum in order to record its electrical activity. In the first series of experiments, subsequently repeated in 12 h fasted animals, CCK8 was infused during the first hour of a 3 hour period of feeding at 2.5, 5 and 10 ng.kg-1.min-1. The same series of infusion were performed 20 min after ICV injection of 2.4 and 10 micrograms.kg-1 of naloxone. CCK8 reduced significantly in a dose related manner the food intake (r = 0.95; P less than 0.01) and the frequency of cyclic spike bursts associated to biphasic contractions of the reticulum observed during feeding (r = 0.89; P less than 0.01). At 5 and 10 ng.kg-1.min-1, the reduction of food intake reached 46.2 and 52.6% during the period of infusion; the basal and stimulated (feeding) frequency of reticular contractions were nearly halved. Previous ICV administration of naloxone (2.4 micrograms.kg-1) partially blocked the effects of CCK8 infusion on both food intake (72%) and reticular frequency (54% basal, 67% stimulated). The CCK8 induced effects on both food intake and frequency of reticular contraction were completely abolished after a previous 10 micrograms.kg-1 injection of naloxone. These results suggest that the central effects of CCK8 on feeding behavior and forestomach motility involve similar central structures and are mediated through opiate receptor structures.     

Systemic and renal hemodynamic responses to vascular blockade of vasopressin in conscious dogs with ascites

A role for arginine vasopressin has been implicated in the compensatory control of arterial blood pressure in several animal models with reported increases in plasma levels of arginine vasopressin. A threefold elevation in plasma vasopressin has been reported in conscious dogs following constriction of the inferior vena cava. In the present study, infusion of the arginine vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine] Arg8-vasopressin into conscious dogs with chronic caval constriction did not decrease mean arterial blood pressure. However, the dose of infused antagonist completely blocked the pressor response to 2 micrograms of exogenous vasopressin. Also the antagonist produced no effect on heart rate, plasma renin activity, or urinary volume and electrolyte excretions. A slight, transient increase (P less than or equal to 0.05) was observed in creatinine clearance and in PAH clearance following antagonist infusion, suggesting a possible decrease in renal vascular resistance. These data suggest that the direct vasoconstrictor actions of vasopressin contribute minimally, if at all, to blood pressure maintenance following chronic caval constriction. Alternatively, blockade of endogenous vasopressin receptors at the level of peripheral arterioles may have resulted in no depressor response due to a masking of this response by other compensatory hormonal and neural pressor systems.     

Effect of parathyroid hormone on renin secretion

The ability of parathyroid hormone (PTH) to increase renin secretion was investigated in pentobarbital-anesthetized dogs. An intravenous infusion of bovine PTH 1-34, at the dose of 0.028 microgram/kg-1 min-1 increased renin secretion by 149% (501 +/- 105 to 1249 +/- 309 ng hr-1 min-1); renin secretion returned to control values during the recovery period. In order to determine whether PTH acted directly on the kidney to increase renin secretion, PTH was infused into the right renal artery at doses of 0.0014 to 0.0028 microgram/kg-1 min-1 and renin secretion from the right kidney was compared to that from the left (control) kidney. Renin secretion from the right (PTH-infused) kidney was not greater than control values for that kidney or different from the renin secretory rate of the left (control) kidney. In contrast, the excretion rates of both phosphate and sodium from the right kidney were greater than control values and from the excretion rates of the left kidney. These data suggest that PTH, while acting directly on the kidney to increase phosphate and sodium excretion, does not elevate renin secretion by a direct renal action.