Circulating angiotensin II is said to inhibit renin release by a direct, intrarenal action. This effect of angiotensin was studied indirectly using the selective angiotensin II antagonist saralasin (1 Sar 8 Ala angiotensin II) in conscious normal, sodium depleted, and sodium loaded rats. Saralasin caused a dose related increase in plasma renin concentration (PRC) in normal and sodium depleted rats, but had no effect on PRC in sodium loaded animals. However, saralasin was 300 times more active in sodium depleted rats than in normal rats. Saralasin caused hypotension and tachycardia in sodium depleted rats, but not in normals. Propranolol inhibited saralasin induced renin release by 99% in normal rats and by 75% in sodium depleted rats but did not alter the hypotensive effect of saralasin in the latter. Saralasin potentiated phentolamine induced renin release, hypotension, and tachycardia in normal rats and this potentiated renin release was blocked by propranolol. The authors conclude that a portion of saralasin elicited renin release in sodium depleted rats is mediated by hypotensive activation of the carotid baroreceptor reflex which increases sympathetic nervous activity in the kidney. However, in sodium depleted rats, saralasin induced a 42 fold increase in PRC, whereas an equipotent hypotensive dose of the vasodilator hydralazine caused only a 3.5 fold increase in PRC. Thus, the authors find that saralasin appears to have a selective effect on renin release over and above its hypotensive effect, which suggests an angiotensin mediated, feedback mechanism inhibitory to renin release, Thus, they have come to the conclusion that for part of saralasin induced renin release appears to be caused by disinhibition of angiotensin suppression of renin secretion. This 'short loop' feedback mechanism is closely associated with intrarenal β adrenergic receptors, since propranolol impaired saralasin induced renin release under all circumstances in their experiments.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine