Hemodynamic and renal effects of ProANF31-67 in hypertensive rats.

It has been demonstrated previously that the atrial natriuretic factor prohormone fragment 31-67 (ProANF31-67) circulates in animals and possesses natriuretic and vasodilating actions. Although the plasma levels of the peptide are reportedly elevated in patients with high blood pressure, its role and actions in hypertension are unknown. In the present study, synthetic human ProANF31-67 was infused intravenously at doses of 0, 10, 30, and 100 ng/kg/min into respective groups of anesthetized normotensive and spontaneously hypertensive rats. Mean arterial pressure (MAP), urine flow rate (UV), and sodium excretion (UNaV) were measured during two consecutive 30-min periods. In both strains of rats, reductions in MAP with ProANF31-67 were similar in magnitude and dose-related. Sodium excretion responses to the peptide infusions also were remarkably similar in both normotensive and hypertensive rats, and the responses demonstrated 3- to 5-fold (P < 0.05) increments compared to control at the doses of 10 and 30 ng/kg/min. However, in the two strains of rats, attenuation of natriuresis occurred with the highest infusion dose of 100 ng/kg/min and was probably related to the large decreases in MAP of 17-23 mmHg at this dose of the peptide. The present results indicate the ProANF31-67 has important hemodynamic and renal effects in hypertension and may represent one compensatory mechanism involved in this disease.     

Natriuresis induced by mild hypernatremia in humans

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 +/- 0.6 to 146.2 +/- 0.5 mmol/l). During Iso a small decrease occurred (142.3 +/- 0.6 to 140.3 +/- 0.7 mmol/l). Iso increased estimates of plasma volume significantly more than Hyper. However, renal sodium excretion increased significantly more with Hyper (291 +/- 25 vs. 199 +/- 24 micromol/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 +/- 0.4 to 3.1 +/- 0.5 pg/ml) and decreased (1.3 +/- 0.4 to 0.6 +/- 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.     

A possible role of atrial natriuretic peptide in ethanol-induced acute diuresis.

The acute effects of ethanol on plasma atrial natriuretic peptide levels were investigated in 4 clinically healthy males, aged 24-26 years, consumed either 750 ml of water as a control study, or the same beverage with 1 ml/kg alcohol added, which increased the plasma alcohol concentration to 99.12 +/- 15.10 mg/dl at 60 min. Plasma atrial natriuretic peptide levels were significantly higher in the alcohol study compared to the control study at each time point (10, 20, 30, 60, 120 min after drinking onset), and with a peak at 10 min. Atrial natriuretic peptide levels showed a positive significant correlation with plasma antidiuretic hormone in the control group, while no relationship was found between the two peptides in the alcohol study. Moreover, a significant correlation exists between plasma atrial natriuretic peptide levels and systolic arterial blood pressure, and heart rate, and between the variations in atrial natriuretic peptide values and the variations in plasma sodium, serum ethanol, and plasma osmolality in the alcohol study. Acute ethanol intake causes an increase in urinary volume, and a decrease in urinary potassium excretion and urinary osmolality, and no change in urinary sodium excretion. These data suggest that acute ethanol administration causes a rapid increase in plasma levels of atrial natriuretic peptide, which could be an important factor of ethanol-induced diuresis. The main mechanisms for increased atrial natriuretic peptide release from atria after acute ethanol ingestion seem to be atrial stretch, due to the increase in arterial blood pressure, in heart rate, in sympathetic tone, and in plasma osmolality, and to a direct secretory effect by antidiuretic hormone.     

Long term reduction in sodium balance: possible additional mechanism whereby nifedipine lowers blood pressure.

OBJECTIVE--To assess the changes in sodium excretion and sodium balance after withdrawal of long term nifedipine. DESIGN--Single blind, placebo controlled study in patients receiving fixed sodium and potassium intakes. SETTING--Blood pressure unit of a teaching hospital in south London. PATIENTS--Eight patients with mild to moderate uncomplicated essential hypertension who had been taking nifedipine 20 mg twice daily for at least six weeks. INTERVENTIONS--Withdrawal of nifedipine and replacement with matching placebo for one week. MAIN OUTCOME MEASURES--Urinary sodium excretion and cumulative sodium balance, body weight, plasma atrial natriuretic peptide concentrations, plasma renin activity and aldosterone concentrations, and blood pressure. RESULTS--During nifedipine withdrawal there was a significant reduction in urinary sodium excretion (day 1: -62.7 mmol/24 h; 95% confidence interval -90.3 to -35.0) and each patient retained a mean of 146 (SEM 26) mmol sodium over the week of replacement with placebo. Body weight and plasma atrial natriuretic peptide concentrations increased during the placebo period and seemed to be associated with the amount of sodium retained. Systolic blood pressure rose from 157 (9) to 165 (9) mmHg (95% confidence interval of difference -7.1 to 22.1) when nifedipine was replaced with matching placebo, and the rise seemed to be related to the amount of sodium that was retained. CONCLUSIONS--Nifedipine causes a long term reduction in sodium balance in patients with essential hypertension. This long term effect may contribute to the mechanism whereby nifedipine lowers blood pressure.     

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.     

Influence of dosage and dietary sodium on the first-dose effects of prazosin.

The effects of the first dose of prazosin were assessed in hypertensive patients on different sodium intakes. Patients received 250, 100, or 30 mmol sodium per 24 hours for a week before taking 2 mg or 0-5 mg prazosin. The acute effects of prazosin on blood pressure and pulse rate were milder with a high sodium intake. On the 100-mmol intake symptomatic postural hypotension occurred in five out of seven patients given 2 mg prazosin and in two out of four given a 0-5-mg dose, whereas those taking 2 mg or 0-5 mg and a 250-mmol sodium intake experienced no postural symptoms. These findings indicate that particular care should be taken in starting prazosin treatment in sodium-depleted patients.     

Responses of the rat pituitary-adrenal axis to hypotensive infusions of corticotropin-releasing factor, vasoactive intestinal peptide and other depressor agents.

We have assessed in male rats the response of the hypothalamo-pituitary-adrenal axis to hypotension induced by 30 min i.v. infusions of corticotropin-releasing factor (CRF; 0.1, 0.2 and 0.5 nmol/kg/min), calcitonin gene-related peptide (CGRP; 0.25 nmol/kg/min), vasoactive intestinal peptide (VIP; 0.25 nmol/kg/min) and nitroprusside (NP; 150 micrograms/kg/min). Infusions of CRF produced dose-dependent decreases in mean arterial blood pressure of 10, 35 and 43 mmHg at 30 min, and the other treatment had depressor effects comparable with the higher CRF doses (between -35 and -44 mmHg). Plasma ACTH levels were increased from 383% to 595% by CGRP, NP and the three different CRF infusions (P less than 0.001 vs. controls), whereas they were raised more than 10-fold by VIP administration (P less than 0.001 vs. other treatments), a level 60% higher than the maximum achieved with CRF. Corticosterone levels were increased by 112% to 146% following infusion of the three different CRF doses, CGRP and NP (P less than 0.001 vs. controls), and by 240% after VIP (P less than 0.001 vs. other treatments). Plasma aldosterone values were increased by 112% to 140% after infusion of NP and the two higher CRF doses (P less than 0.01 vs. controls), and by 223% following VIP (P less than 0.05 vs. CRF 0.2 and NP). CGRP infusion, although resulting in similar haemodynamic changes, did not alter circulating aldosterone. The levels measured after CGRP were identical to those observed after the infusion of atrial natriuretic peptide (ANP; 1 nmol/kg/min), a known inhibitor of aldosterone secretion. These results demonstrate that the combination of hypotension and direct pituitary stimulation by CRF does not increase circulating ACTH levels above those obtained with hypotension alone (NP and CGRP), whereas VIP, which has only minimal direct effects on corticotroph function, markedly enhanced the ACTH response, suggesting that it may modulate ACTH release by an indirect mechanism. Evaluation of aldosterone levels after the different infusions indicates that CGRP prevented the rise normally associated with acute hypotension, thus confirming recent observations in other species that stimulated aldosterone secretion can be inhibited by CGRP.     

Diuretic, natriuretic and hypotensive effects of synthetic atrial natriuretic factor in conscious newborn calves

The effects of synthetic Atrial Natriuretic Factor (ANF) on urine flow rate, sodium excretion, potassium excretion and arterial blood pressure were studied in 10-12 days-old female calves. In four female calves fitted with a Foley catheter, an intravenous administration of ANF (Ile-ANF 26; 1.6 micrograms/kg body wt during 30 min) induced an increase (P less than 0.01) in urine flow rate (from 1.8 +/- 0.2 to 12.8 +/- 1.1 ml/min), sodium excretion (from 0.15 +/- 0.02 to 0.81 +/- 0.06 mmol/min) and free water clearance (from 0.13 +/- 0.9 to 5.16 +/- 0.5 ml/min). It had no significant effect on potassium excretion. In four calves chronically-instrumented with a carotid catheter, an intravenous administration of synthetic ANF alone (1.6 micrograms/kg body wt during 30 min) induced a gradual decrease (P less than 0.01) in systolic, diastolic and mean arterial blood pressure (from 112 +/- 4 to 72, from 72 +/- 2 to 61 +/- 1 and from 90 +/- 2 to 65 +/- 2 mmHg respectively, at the end of ANF infusion). An intravenous administration of angiotensin II (AII) (0.5 micrograms/kg body wt during 45 min) induced a significant increase in systolic, diastolic and mean arterial blood pressure which was antagonized by an i.v. bolus injection of ANF (0.125 micrograms/kg body wt). However, during a simultaneous administration of AII (0.3 micrograms/kg body wt during 30 min) and ANF (1.6 micrograms/kg body wt. during 30 min), the atrial peptide did not influence the pressure action of AII. These findings indicate that the conscious newborn calf is sensitive to diuretic, natriuretic and hypotensive effects of synthetic ANF.     

Cardiovascular and renal effects of eel and rat atrial natriuretic peptide in rainbow trout,Salmo gairdneri

Summary The renal and in vitro vascular effects of atrial natriuretic peptides have been examined in seveal species of fish. However, comparatively few investigations have described the effects of these peptides on the cardiovascular system in vivo. In the present experiments the dorsal aorta and urinary bladder were cannulated and the effects of atrial natriuretic peptides from rat and eel were monitored in conscious trout during bolus injection or continuous atrial natriuretic peptide infusion. The results show that the initial pressor effect of atrial natriuretic peptides is independent of environmental salinity adaptation (fresh or seawater) and the chemical form of atrial natriuretic peptide injected, but it is affected by the rate of atrial natriuretic peptide administration. This pressor response, and the accompanying diuresis, are mediated through -adrenergic activation. Continuous infusion of either rat or eel atrial natriuretic peptide produces a steady fall in mean arterial blood pressure, which is temporally preceded by an increase in heart rate and a decrease in pulse pressure. Diuresis induced by atrial natriuretic peptides is only partially sustained during continuous infusion. Propranolol partially blocks the increase induced in heart rate by atrial natriuretic peptides, but does not affect either pulse pressure or mean arterial pressure. Propranolol significantly increases urine flow in saline-infused animals but has no apparent effect on animals subjected to infusions of atrial natriuretic peptides. These results indicate that there are multiple foci for the action of atrial natriuretic peptides in trout and that in many instances the effects of atrial natriuretic peptides are mediated through secondary effector systems.Abbreviations ANP atrial natriuretic peptide - bw body weight - PBS phosphate-buffered saline     

Atrial natriuretic factor (ANF) increases urinary protein excretion in patients with essential hypertension: a possible role of ANF for renal handling of protein

Low dose iv infusion (0.01 and 0.03 micrograms/kg per min, for 30 min each) of alpha-human atrial natriuretic factor (alpha-hANF) produced a significant increase (+300%) in urinary protein excretion in patients with essential hypertension but not in normotensive controls, when their renal function was normal. The major component of excreted proteins induced by alpha-hANF infusion was presumed to be albumin on the basis of molecular weight (69,000) analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Urine output and sodium and potassium excretion rates were increased dose-dependently by alpha-hANF infusion in the hypertensive patients in a similar fashion to those in the controls. Glomerular filtration rate (GFR) remained unchanged in the controls but was slightly increased in the patients (+33%) during the infusion. These results suggest that besides its previously recognized physiological functions such as natriuresis and diuresis, ANF plays an important role in the regulation of renal handling of proteins in patients with essential hypertension.     

Clonidine and morphine increase atrial natriuretic peptide secretion in anesthetized rats

In order to determine whether the activity of central alpha 2-adrenergic and opioid receptors influence plasma atrial natriuretic peptide (ANP) levels, clonidine and morphine were infused into the lateral cerebral ventricle for 45 min in anesthetized Sprague-Dawley rats. The central administration of a low dose of clonidine (10 ng/min) caused a significant increase in plasma ANP without changing arterial blood pressure or central venous pressure. Pretreatment with yohimbine (5 micrograms/min) completely blocked the effect of clonidine. Central infusion of morphine (100 ng/min) also elevated plasma ANP levels and naloxone (5 micrograms/min) blunted this effect. Intravenous infusion of the same dose of clonidine or morphine did not affect plasma ANP levels. Moreover, the effect of clonidine on plasma ANP was partially blocked by pretreatment with naloxone (5 micrograms/min). These results suggest that central alpha 2-adrenergic and opioid receptors may be involved in ANP secretion.     

Evaluation of SQ 28,603, an inhibitor of neutral endopeptidase, in conscious monkeys.

The potent neutral endopeptidase inhibitor SQ 28,603 (N-(2-(mercaptomethyl)-1-oxo-3-phenylpropyl)-beta-alanine) significantly increased excretion of sodium from 4.9 +/- 2.3 to 14.3 +/- 2.1 muequiv./min and cyclic 3',5'-guanosine monophosphate from 118 +/- 13 to 179 +/- 18 pmol/min after intravenous administration of 300 mumol/kg (approximately 80 mg/kg) in conscious female cynomolgus monkeys. SQ 28,603 did not change blood pressure or plasma atrial natriuretic peptide concentrations in the normal monkeys. In contrast, 1-h infusions of 3, 10, or 30 pmol.kg-1.min-1 of human atrial natriuretic peptide lowered blood pressure by -3 +/- 4, -9 +/- 4, and -27 +/- 3 mmHg (1 mmHg = 133.322 Pa), increased cyclic guanosine monophosphate excretion from 78 +/- 11 to 90 +/- 6, 216 +/- 33, and 531 +/- 41 pmol/min, and raised plasma atrial natriuretic peptide from 7.2 +/- 0.7 to 21 +/- 4, 62 +/- 12, and 192 +/- 35 fmol/mL without affecting sodium excretion. In monkeys receiving 10 pmol.kg-1.min-1 of atrial natriuretic peptide, 300 mumol/kg of SQ 28,603 reduced mean arterial pressure by -13 +/- 5 mmHg and increased sodium excretion from 6.6 +/- 3.2 to 31.3 +/- 6.0 muequiv./min, cyclic guanosine monophosphate excretion from 342 +/- 68 to 1144 +/- 418 pmol/min, and plasma atrial natriuretic peptide from 124 +/- 8 to 262 +/- 52 fmol/mL. In conclusion, SQ 28,603 stimulated renal excretory function in conscious monkeys, presumably by preventing the degradation of atrial natriuretic peptide by neutral endopeptidase.     

Sodium intake influences the effects of atriopeptin on blood pressure and transcapillary fluid shift in the rat

The influence of chronic changes in sodium intake on the acute effects of atrial natriuretic peptide (ANP) on arterial pressure and fluid translocation was assessed in acutely binephrectomized rats. After 3 weeks of either low sodium or high sodium diet, animals were administered ANP at doses of 0.1 and 1 microgram/kg/min. A marked and irreversible hypotensive response to ANP was observed with the higher infusion rate in the low sodium group, whereas blood pressure did not change significantly in the other groups. The effect of ANP on plasma protein concentration was less marked than that on hematocrit in all groups and was not significantly affected by sodium intake. The effect of both doses of ANP on hematocrit was enhanced in the high sodium group, indicating that the fluid shift out of the intravascular compartment was magnified by high sodium intake.     

Effect of atrial natriuretic factor on arterial blood pressure and frequency of heart contraction in rats with genetically determined hypertension and in normotensive rats

An effect of peptide released by the heart atria of mammals and called the atrial natriuretic factor (ANF) on blood pressure and heart contractions was studied in rats with genetically determined arterial hypertension (SHR) and in normotensive Wistar-Kyoto rats (WKY). Nine male SHR rats and 11 male WKY rats, aged between 12 and 16 weeks, were given normal saline infusion for 30 minutes through implanted catheters to both ulnar vein and artery. Then, an infusion of ANF at the rate of 0.3 microgram/kg per hour followed for 35 minutes. An infusion of ANF produces significant decrease in the mean arterial blood pressure, systolic and diastolic pressures without significant effect on pulse pressure and heart contractions. AFN infusion with the same rate did not produce any significant differences in the arterial blood pressure and heart contractions in Wistar-Kyoto rats. The obtained results suggest that ANF may play a role in pathogenesis of the arterial blood hypertension.     

Effect of a chronic infusion of atrial natriuretic peptide on sodium balance in normotensive and two-kidney, one-clip hypertensive rats

We have previously found that chronic infusion of atrial natriuretic peptide (ANP) decreased mean arterial pressure (MAP) by 16% in two-kidney, one-clip (2K-1C) hypertensive rats, and we hypothesized that natriuresis might be modified through the pressure-natriuresis mechanism. We therefore decided to evaluate sodium balance in 2K-1C rats infused with ANP (0.5 micrograms/h for 4 days). The ANP infusion to the 2K-1C rats induced a significant decrease in MAP from 171 +/- 3 to a minimum value of 147 +/- 6 mm Hg after 2 days of treatment (p less than 0.001). Sodium excretion fell from 2,536 +/- 60 to 2,047 +/- 86 (p less than 0.001) and 2,211 +/- 96 mu Eq/24 h (p less than 0.05) by days 1 and 2 of ANP administration. Furthermore, fractional excretion of sodium intake decreased from 99.1 +/- 1.5 to 81.1 +/- 2.9 (p less than 0.001), 84.1 +/- 2.6 (p less than 0.05) and 85.9 +/- 5.15% (p less than 0.05) by days 1, 2 and 3 of ANP infusion, respectively, returning to basal values thereafter. The administration of vehicle (0.9% NaCl) did not induce any significant change in 2K-1C hypertensive rats. The infusion of either vehicle or the same dose of ANP to normotensive rats (0.5 micrograms/h, for 4 days) did not modify sodium balance throughout the experiment. These results strongly suggest that the ANP-induced decrease in MAP might be responsible for the transitory sodium retention observed in 2K-1C hypertensive rats during the administration of the peptide.     

The effects of intracerebroventricular infusion of atrial natriuretic factor in conscious sheep

The effects of 24-hour intracerebroventricular infusion of human atrial natriuretic factor (ANF) and two related fragments were studied in conscious sheep. ANF (1-28) had no effect on either mean arterial pressure (MAP) or heart rate (HR) when infused at 3 or 10 micrograms/hr, however a small diuresis and an increase in urinary sodium (Na) excretion was observed. The smaller fragment, ANF (5-27) infused at 10 micrograms/hr, increased MAP, HR and body temperature, although the same rate of infusion of ANF (5-28) was without effect. All peptides increased plasma sodium concentration and plasma osmolality. None of the peptides affected plasma ACTH, glucose or renin concentration. ANF (1-28) had no effect on either Na intake or water intake in Na-depleted sheep. These studies suggest that members of the ANF family can influence a number of physiological functions following central administration.     

Cardiac natriuretic peptides and pancreatic islet blood flow in anesthetized rats.

The aim of the study was to evaluate effects of cardiac natriuretic peptides on splanchnic circulation, especially to the pancreatic islets. Pentobarbital-anesthetized rats were infused intravenously (0.01 ml/min for 20 min) with saline, atrial natriuretic peptide (ANP; 0.25 or 0.5 microg/kg BW/min), brain natriuretic peptide (BNP; 0.5 microg/kg BW/min) or C-type natriuretic peptide (CNP; 0.5 or 2.0 microg/kg BW/min). Splanchnic blood perfusion was then measured with a microsphere technique. Mean arterial blood pressure was decreased by ANP and BNP, but not by CNP. The animals given the highest dose of ANP became markedly hypoglycemic, whilst no such effects were seen in any of the other groups of animals. Total pancreatic blood flow was decreased by the highest dose of CNP, whereas no change was seen after administration of the other peptides. Islet blood flow was increased by the highest dose of ANP. Neither BNP nor CNP affected islet blood flow. None of the natriuretic peptides influenced duodenal, colonic or arterial hepatic blood flow. It is concluded that cardiac natriuretic peptides exert only minor effects on splanchnic blood perfusion in anesthetized rats. However, islet blood perfusion may be influenced by ANP.     

Atrial natriuretic peptides in man

Research on the physiological role of atrial peptides in man is limited, and the potential for these peptides, or more stable analogues, in therapeutics is uncertain. It is clear, however, that plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) are increased in volunteers taking a high sodium diet, and are elevated in patients with heart failure, chronic renal failure, and primary aldosteronism. There is suggestive evidence that IR-ANP levels are increased also in essential hypertension, although overlap with normotensives is considerable. Injection or infusion of atrial peptides into man results in a diuresis, an increased output of urine electrolytes, a fall in blood pressure and a rise in heart rate, suppression of aldosterone and sometimes of renin also, and stimulation of norepinephrine. In essential hypertensives, urinary effects may be greater than in normotensives. Heart failure patients show a rise in cardiac output and falls in both systemic and pulmonary arterial pressure. Over the next few years and especially if specific antagonists can be developed, the physiologic and pathophysiologic roles of atrial peptides in normal man and in clinical disorders should be clarified. It is possible that stable analogues of atrial peptides will find a place in the treatment of cardiac failure, renal failure, and perhaps hypertension.     

Renal actions of atrial natriuretic peptide on the postischemic kidney

The objective of this study was to evaluate the renal actions of atrial natriuretic peptide (ANP) in the unilateral postischemic kidney of anesthetized dogs with a severe reduction in glomerular filtration rate. The dose of atrial natriuretic peptide (50 ng.kg-1.min-1) we gave did not alter the mean systemic arterial pressure, renal blood flow, and glomerular filtration rate in the normal kidney, as determined in foregoing studies. ANP was infused into the intrarenal artery continuously for 60 min after the release from 45 min of complete renal artery occlusion. In the vehicle-infused group, the glomerular filtration rate fell dramatically (6% of control), the renal blood flow decreased (60% of control), and the mean systemic arterial pressure tended to increase (136% of control). The urine flow rate and urinary excretion of sodium decreased significantly (25 and 25%, respectively) at 30 min after reflow in the postischemic period. Continuous renal artery infusion of ANP resulted in a marked increase in urine flow rate (246% of control) and the urinary excretion of sodium (286% of control). The administration of ANP led to an improvement in renal blood flow (99% of control) and glomerular filtration rate (40% of control), and attenuated the rise in mean systemic arterial pressure (109% of control), compared with findings in the vehicle-infused group. Plasma renin activity and prostaglandin E2 concentration in the renal venous blood were elevated after the release from complete renal artery occlusion in both groups. These results indicate that the vascular effects of ANP on the postischemic kidney were enhanced and that the peptide maintained the natriuretic effect.     

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.