Evidence for β-Adrenergic Regulation of Renal and Extrarenal Plasma Prorenin and Renin in Dogs 1

Abstract

Abstract

Beta blockade with propranolol for 7 days in healthy normotensive dogs produced a sustained 20-25% drop in heart rate, but only a transient suppression of blood pressure. Plasma renin activity and prorenin were also suppressed transiently, suggesting that both are under β-receptor regulation. Bilateral nephrectomy (2NX) was followed by rapid clearance of renin from the circulation, at a rate that was minimally influenced by β blockade. In contrast, the plasma prorenin level rose markedly to a peak within an hour after surgery, leveled off during the next 24 hr, dropped almost toward the pre-2NX baseline by 48 hr, but proceeded to rise again between 48 and 120 hr. Propranolol administration before and during the 2NX period reduced the detectable prorenin, suggesting that its extrarenal source is under β-adrenergic regulation. The rapid increment of prorenin after 2NX suggests that extrarenal prorenin may have constituted part of the total plasma prorenin before 2NX, and/or had developed sufficiently quickly afterwards to replace and exceed the disappearing renal prorenin. Any fresh increment beyond 48 hr could presumably have been only extrarenal. These observations suggest the existence of a rich β-regulated extrarenal source of prorenin capable of rapidly supplying the plasma. However, no renin-angiotensin was apparently produced from this prorenin in the nephrectomized state, implying the lack of renal “convertase”, without which the prorenin convertase mechanism as a whole was rendered ineffective. The source of the extrarenal prorenin and the identity of the renal convertase remain to be established.