The effects of altered sodium balance and adrenergic blockade on renin release induced in rats by angiotensin antagonism. Circ Res 1976 Jun;38(6):531-9
Date
06/01/1976Pubmed ID
1269103DOI
10.1161/01.res.38.6.531Scopus ID
2-s2.0-0017198850 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
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.
Author List
Keeton TK, Pettinger WA, Campbell WBAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Desoxycorticosterone
Dose-Response Relationship, Drug
Feedback
Hydralazine
Hyponatremia
Kidney
Kinetics
Male
Propranolol
Rats
Receptors, Adrenergic
Renin
Saralasin
Sodium
Time Factors
