Renal, endocrine and vascular effects of atrial natriuretic peptide in a novel vasopressin‐deficient genetically hypertensive strain of rat

Abstract

SUMMARYIn the absence of the potentially confounding influence of vasopressin in hypertension, the effects of atrial natriuretic peptide (ANP) on arterial blood pressure and renal handling of water and sodium were assessed from comparison of responses to intravenous ANP infusion in anaesthetized vasopressin-deficient New Zealand genetically hypertensive (DI/H) rats and their normotensive substrain (DI/N). After 320 min of hypotonic saline infusion, plasma ANP concentration was significantly higher in DI/H compared with DI/N rats. ANP administration increased circulating ANP concentration in both groups. Plasma angiotensin II concentration was higher in DI/H than in DI/N rats; infusion of ANP raised circulating angiotensin II in both groups though this achieved statistical significance only in DI/N rats. Plasma aldosterone concentrations were initially similar in normotensive and hypertensive animals and, in both, were reduced markedly by i.v. ANP infusion. Administration of ANP produced sustained hypotension in both groups. However, the hypotensive effect of ANP was more pronounced in DI/H compared with DI/N rats. Heart rate was initially similar in the two groups, and infusion of ANP produced no detectable change. By comparison with animals maintained on hormone-free infusate, urine flow increased markedly over the 80 min period of ANP infusion in both groups, by 142 % in DI/H rats and 127 % in DI/N rats. ANP administration produced a natriuresis in both groups but the increase in Na+ excretion was much greater in DI/H (342 %) than in DI/N (139 %) rats. It appears from the current study that vasopressin-deficient hypertensive rats are more sensitive to ANP with regard to effects on blood pressure and renal excretion than their vasopressin-deficient normotensive substrain. These differences may, in part, reflect adjustments to long-term elevation in blood pressure and in plasma ANP concentration in hypertension and, in part, rely on the associated disturbances in related endocrine systems.

Regional haemodynamic effects of antagonists of angiotensin II, endothelin and adrenoceptors in conscious, vasopressin‐deficient, genetically hypertensive rats

“…Indeed, it appears that All is relatively less involved in cardi-ovascular control in DI/H than in DI/N rats in volume-replete conditions, in spite of the former having higher plasma All levels (Al-Barazanji & Balment, 1995). The relatively small hindquarters vasodilator effect of losartan, compared to its clear renal and mesenteric vasodilator action is consistent with the haemodynamic profile of exogenous All (Gardiner et al, 1988).…”

“…However, following water deprivation, or hypovolaemia induced by subcutaneous injection of a hyperoncotic solution of polyethylene glycol (PEG), the maintenance of systemic arterial blood pressure becomes abnormally dependent on the RAS (Gardiner & Bennett, 1985;1986;Gardiner et al, 1989;Muller et al, 1990;Batin et al, 1991a,b). These observations, together with the finding that vasopressin-deficient, genetically hypertensive rats (DI/H; obtained by cross-breeding male New Zealand hypertensive rats with female Brattleboro rats (Ashton & Balment, 1989) have higher plasma angiotensin II (AII) levels than their normotensive controls (DI/N; Al-Barazanji & Balment, 1995), raise the possibility that the maintenance of hypertension in the DI/H rat is due to hyperactivation of the RAS. However, in such a case it does not follow that the elevation in blood pressure would be dependent, directly, on the vasoconstrictor action of angiotensin II.…”