Vasodilating antihypertensive drug-induced aldosterone release--a study of endogenous angiotensin-mediated aldosterone release in the rat.
The vasodilatory drugs, minoxidil and hydralazine, induce renin release in the rat, man and the dog. Previous reports suggest that the rat adrenal cortex was insensitive to angiotensin stimulation. As a result these studies were designed to obtain evidence for or against the hypothesis that the control of aldosterone release in the rat is unique among mammalian species. Minoxidil and hydralazine induced a time-related increase in both serum renin activity and serum aldosterone. Minoxidil caused a dose-related, proportional increase in serum renin and aldosterone. This response was blocked by prior bilateral nephrectomy but was not affected by hypophysectomy. A competitive angiotensin antagonist, saralasin (1-Sar-8-Ala angiotensin II), impaired minoxidil-induced aldosterone release in a dose-related manner while potentiating minoxidil-induced renin release. Pretreatment with propranolol, a beta adrenergic blocking drug, impaired minoxidil-induced renin and aldosterone release. Only small changes in serum corticosterone occurred after minoxidil or hydralazine administration. These results indicate that minoxidil-induced aldosterone release was mediated by the endogenous angiotensin II formed from renin release. They also support the unanesthetized rat as an appropriate animal model for study of the renin-angiotensin-aldosterone axis and its modification by drugs.
D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D006830:Hydralazine / Q000494:pharmacology; D007016:Hypophysectomy; D007668:Kidney / Q000502:physiology; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D009392:Nephrectomy; D010902:Pituitary Gland / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000097:blood / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D006830:Hydralazine; D000450:Aldosterone; D008914:Minoxidil; D011433:Propranolol; D012083:Renin; D012504:Saralasin; D003345:Corticosterone