Abstract

Previous studies have indicated that the hypotensive effects of atrial natriuretic factor were enhanced in renin-dependent hypertensive rats, suggesting that the atrial peptides may antagonize the vasoconstrictor effects of the renin-angiotensin system. The present study was designed to define further the interaction between atrial natriuretic factor and the renin-angiotensin system by examining the hemodynamic effects of Wy-47,663, a synthetic human atrial natriuretic factor, in conscious normotensive rats, in renin-dependent (aortic-ligated) hypertensive rats, and in rats made hypertensive by chronic infusion of angiotensin II. Changes in renal and mesenteric blood flow were continuously monitored in the rats using pulsed Doppler flow probes chronically implanted in the animals one week prior to testing. Infusion of increasing doses of Wy-47,663 caused dose-dependent reductions in mean arterial pressure in all three groups of rats, but the depressor responses were significantly greater in renal hypertensive and angiotensin II-infused rats. Renal blood flow tended to increase during the infusion of the atrial peptide in the angiotensin II-treated rats, and renal vascular resistance fell significantly (-37 +/- 6%). However, Wy-47,663 significantly reduced renal blood flow in the normotensive and renal hypertensive rats, while renal vascular resistance was increased (29 +/- 6%) and unchanged (3 +/- 9%), respectively. Mesenteric blood flow was reduced significantly, and mesenteric vascular resistance was increased markedly in all three groups of rats during infusion of the atrial peptide. In a separate group of renal hypertensive rats, the hemodynamic effects of complete blockade of the renin-angiotensin system were assessed by injection of an angiotensin II converting enzyme inhibitor (Wy-44,655).(ABSTRACT TRUNCATED AT 250 WORDS)

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