Plasma Renin in Chronic Experimental Heart Failure and during Renal Sodium "Escape" from Mineralocorticoids

Abstract

A striking increase in the plasma renin level occurred in dogs with low output right heart failure secondary to tricuspid insufficiency and pulmonic stenosis and in three of five animals with high output failure produced by a large arteriovenous fistula. When dogs with a small arteriovenous fistula were given daily injections of DOCA, the renal sodium "escape" phenomenon occurred. In these animals, the level of plasma renin was suppressed during DOCA administration both during the initial period of sodium retention and also later when sodium balance was normal or negative. In contrast, when dogs with a larger arteriovenous fistula but without evidence of cardiac failure were given DOCA, they retained sodium and developed signs of congestive heart failure. However, in these animals with congestion and ascites, in contrast to-the dogs that developed spontaneous high output failure, the plasma renin was low. Renin-substrate was unaltered in all of the experimental situations studied except for the decrease observed in dogs with low output right heart failure, la these animals, it seems likely that decreased renin-substrate was secondary to hepatic congestion and liver damage. The renin-angiotensin system does not seem to be related to the "escape" phenomenon, and renin does not appear to be the factor that makes the kidney unusually responsive to mineralocorticoids. Thus, in experimental heart failure the reninangiotensin system was activated, but in the congestive syndrome produced by DOCA the plasma renin level was suppressed. ADDITIONAL KEY WORDSrenin-angiotensin system arteriovenous fistula desoxycorticosterone sodium balance renin-substrate tricuspid insufficiency and pulmonic stenosis high output failure conscious dogs• Hypersecretion of aldosterone is common in edematous states (1-12). Many patients with congestive heart failure have increased secretion and excretion of aldosterone (1, 3-7), but patients with edema also have normal rates of secretion, of this hormone (8-10). Experimental heart failure in dogs is regularly accompanied by an increase in aldosteroneFrom the Departments of Physiology and Surgery, University of Missouri School of Medicine, Columbia, Missouri 6520X.This investigation was supported in part by U. S. Public Health Service Research Grant HE 10612-01 from the National Heart Institute.Dr. Johnston is Research Fellow, National Heart Foundation of Australia.Accepted for publication December 10, 1967. secretion and a high plasma level of aldosterone (2,11,12). The increase in plasma aldosterone in heart failure also results from a decrease in the metabolic clearance of aldosterone by the Ever (4, 9, 13). The present study relates the participation of the reninangiotensin system in experimental heart failure to sodium balance and to the known hypersecfetion of aldosterone. This investigation is also concerned with the role of the renin-angiotensin system in the "escape" phenomenon (14-15). Normal humans or animals given large quantities of a mineralocorticoid retain sodium for only ...

Urinary Sodium Excretion and Proximal Tubule Reabsorption in Rats with High-Output Heart Failure

“…Enhanced sodium reabsorption by the proximal tubule has been thought to be the mechanism causing sustained salt retention in dogs with an aortato-vena cava fistula [11]. Our data demonstrate that reabsorption by the proximal tubule was indeed enhanced in the A-V fistula rats.…”

“…From clearance determinations in patients with edema of different origin, Bell et al [6] and Schedl and Barrter [22] have concluded that the major site of salt and water retention is the proximal tubule. Similarly, an enhanced rate of sodium reabsorption by the proximal tubule has been suggested to be the mechanism causing salt retention in dogs with either high-output heart failure [11] or thoracic caval constriction [7], However, recent micropuncture studies in dogs with edema and ascites due to an aorta-to-vena cava fistula [23] or to chronic caval constriction [3,17] have clearly demonstrated that proximal tubular function is normal in these models of salt retention with regard to both fractional and absolute sodium reabsorption. Furthermore, the limited natriuretic response of these animals to acute extracellular fluid volume expansion is not caused by failure to decrease sodium reabsorption in the proximal tubule [3,17,23].…”

Plasma concentrations of angiotensin II and aldosterone during acute left ventricular failure in the dog. Effect of converting enzyme inhibition

“…Activation of the RAA system has been demonstrated in chronic and subacute forms of experimental heart failure [2,15,19,27]. It has been shown clinically in complicated acute myocardial infarction [22] and in chronic congestive heart failure [5,9,12,14,24].…”

Renin and the Kidney

“…Genest et al [37] used a balloon to transiently obstruct venous return to the right atria of dogs and found a three fold increase in plasma renin activity. Johnston et al [52] found increased plasma renin levels in dogs with low cardiac output secondary to tricuspid insufficiency and pulmonic stenosis. In dogs with arteriovenous fistulas and high output cardiac failure, three of five animals showed increased plasma renin activity [52], In DOCA-treated dogs which developed a venous con gestive state after the creation of arteriovenous fistula, but did not have elevated right atrial pressures plasma renin activity remained low [52], Davis et al [100] using larger arteriovenous fistulas in dogs demonstrated consistent rise in renin secretion from 600 to 2,000 ng A/min.…”

“…Johnston et al [52] found increased plasma renin levels in dogs with low cardiac output secondary to tricuspid insufficiency and pulmonic stenosis. In dogs with arteriovenous fistulas and high output cardiac failure, three of five animals showed increased plasma renin activity [52], In DOCA-treated dogs which developed a venous con gestive state after the creation of arteriovenous fistula, but did not have elevated right atrial pressures plasma renin activity remained low [52], Davis et al [100] using larger arteriovenous fistulas in dogs demonstrated consistent rise in renin secretion from 600 to 2,000 ng A/min. D avis et al [13] have also demonstrated that the mechanism of increased renin release with caval con striction in dogs with nonfiltering kidneys is mediated by a baroreceptor mechanism.…”