Control of renin secretion in the anesthetized dog

Abstract

Renin concentrations of renal venous plasma were indirectly measured by bio-assaying the pressor activity produced by plasma incubation under standardized conditions. Pressor activity was detectable in 85% of control dogs, was reciprocally related to sodium excretion, but did not correlate with arterial blood pressure. Reduction of mean renal arterial pressure to 90 mm Hg by an aortic clamp decreased sodium excretion and produced sustained increases in renin secretion and arterial blood pressure proximal to the clamp. Release of the aortic clamp resulted in gradual return of these variables toward control values. Induction of diuresis (osmotic diuretics, chlorothiazide, or acetazolamide) prior to aortic clamping minimized or completely prevented the usual clamp-induced rises in renin secretion and proximal blood pressure. Induction of diuresis during aortic clamping returned the elevated renin secretion and proximal blood pressure toward control values. These effects of diuretics could not be explained by changes in renal hemodynamics or plasma composition. Elevation of ureteral pressure in nondiuretic dogs also increased renin secretion and arterial blood pressure. We conclude that renin secretion is not controlled by blood pressure, per se, or intrarenal pressure, but by the flow or composition of intratubular fluid, probably at the level of the macula densa.

Effects of EDTA and verapamil on renin release in dogs.

“…The increased sodium load to the macula densa may be responsible for the increase in renin release since Thurau and associates (17) have presented evidence that increased sodium concentration at the macula densa increases renin release. However, a number of papers indicate an inverse relationship between sodium load to the macula densa and renin release (18). In the present experi ment, verapamil in combination with ouabain infusion caused a significant increase in renin release without any additional changes in sodium excretion.…”

Central components of the renin‐angiotensin system

“…The observations of Lewis, Leo & Prinzmetal (1941) that re-establishment of the renal circulation after several hours ischaemia results in a pressor response in rats (Lowe, 1964;Vander & Miller, 1964;McKenzie, Cook & Lee, 1966) and confirms that it is a reduction in renal arterial blood pressure rather than ischaemia which results in the release of a pressor substance. That the pressor response results from the release of renin after re-establishment of the circulation was demonstrated by the identification of angiotensin in the blood and by the occurrence of tachyphylaxis to angiotensin II.…”

Furosemide stimulates renin expression in the kidneys of salt-supplemented rats

“…The late thick ascending limb of Henle (TALH) including the macula densa is considered to play an important role in the regulation of renin secretion, an effect that is thought to be mediated by the NaC1 transport of these [8,24,28]. Thus it has been demonstrated that renin secretion from a single juxtaglomerular apparatus is inversely related to the concentration of sodium chloride in the tubular fluid facing the macula densa [17,26].…”