title: The effects of altered sodium balance and adrenergic blockade on renin release induced in rats by angiotensin antagonism.
abstract: 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 (1Sar-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 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. We 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, we 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, we 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" feed-back mechanism is closely associated with intrarenal beta-adrenergic receptors, since propranolol impaired saralasin-induced renin release under all circumstances in our experiments.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005246:Feedback; D006830:Hydralazine / Q000494:pharmacology; D007010:Hyponatremia / Q000201:enzymology; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic; D012083:Renin / Q000097:blood / Q000378:metabolism*; D012504:Saralasin; D012964:Sodium / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011941:Receptors, Adrenergic; D006830:Hydralazine; D003900:Desoxycorticosterone; D012964:Sodium; D011433:Propranolol; D012083:Renin; D012504:Saralasin