Antihypertensive and aldosterone-lowering effects of synthetic atrial natriuretic factor in renin-dependent renovascular hypertension.
A 24-amino acid residue synthetic atrial natriuretic factor (ANF) antagonizes angiotensin II-induced vascular contractility and aldosterone production in isolated blood vessels and adrenal cells, respectively. To determine the significance of these effects in vivo, the blood pressure and aldosterone responses to synthetic ANF were evaluated in rats with two-kidney, one clip hypertension (n = 5) and in sham-operated controls (n = 4). In the latter, ANF caused a slight fall in mean blood pressure (-7 +/- 3%) and inconsistent changes in plasma renin and aldosterone. In hypertensive rats, ANF decreased blood pressure by 31 +/- 7 mmHg (17 +/- 3%), comparable to the effect of the angiotensin antagonist saralasin (31 +/- 4 mmHg). Plasma renin activity increased from 48 +/- 15 to 79 +/- 23 ng/ml/h. Despite this, ANF caused marked suppression of plasma aldosterone (from 97 +/- 28 to 20 +/- 8.9 ng/100 ml). These results show that ANF can exert potent antihypertensive and aldosterone-lowering effects in vivo, at least when the renin-angiotensin system is stimulated.
D000450:Aldosterone / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006978:Hypertension, Renovascular / Q000097:blood / Q000188:drug therapy*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood*; D012504:Saralasin / Q000494:pharmacology
D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin; D012504:Saralasin