Mechanisms of sodium retention in heart failure: relation to the renin-angiotensin-aldosterone system

Abstract

Renal plasma flow (RPF), glomerular filtration rate (GFR), renal proximal tubular delivery of sodium and water evaluated by lithium clearance, and hormonal parameters were measured in 12 patients with congestive heart failure NYHA class II-IV before and after captopril treatment for 4 wk and in 13 healthy control subjects. RPF and GFR were significantly decreased in heart failure, whereas the filtration fraction (FF) was increased. Treatment with captopril increased RPF and decreased FF, whereas GFR was unchanged. Total and fractional urinary excretion of sodium were reduced in the patients compared with the controls, but increased after captopril. Fractional excretion of lithium was normal in heart failure and was increased by captopril. Atrial natriuretic peptide, guanosine 3',5'-cyclic monophosphate, and aldosterone in plasma were significantly elevated in heart failure and were reduced by treatment with captopril. Plasma renin activity was increased in patients, correlated inversely with RPF, and increased further after captopril treatment. It is concluded that the reduced sodium excretion in heart failure was caused by a combination of diminished glomerular filtration and enhanced tubular reabsorption beyond the proximal tubule and that treatment with captopril increased urinary sodium excretion partly due to an attenuated sodium reabsorption in the proximal tubule. The present data in patients with congestive heart failure are consistent with an increased intrarenal angiotensin II generation and an elevated plasma level of aldosterone being involved in the pathogenesis of the glomerular hemodynamic changes and the enhanced distal tubular reabsorption, respectively.

Endothelial Function Predicts the Development of Renal Damage after Combined Nephrectomy and Myocardial Infarction

“…UNx already represents a state of mild renal damage as the hemodynamic adaptations occur in the remaining glomeruli to compensate for the nephron loss. Several mechanisms by which MI accelerates mild renal damage may be hypothesized, including neurohumoral activation occurring after the MI and subsequent heart failure (8,9), the endothelial dysfunction of the systemic arteries (10,11), or the generalized inflammatory reaction that is associated with acute MI. Our data, however, indicate that the renal effects of MI depend, at least partially, on intrarenal factors that are present before the injury (MI) triggers renal damage.…”

Changes of renal AQP2, ENaC, and NHE3 in experimentally induced heart failure: response to angiotensin II AT1receptor blockade

“…53). Thus in HF activation of RAAS may become a maladaptive response to arterial underfilling, introducing a vicious cycle leading to increasing morbidity and mortality (17). As a consequence, a variety of pharmaceutical efforts have targeted the RAAS.…”

“…Studies in HF patients and in experimentally induced rat models have revealed dysregulation of some of the renal sodium transporters indicating enhanced sodium reabsorption in the proximal tubule (59) and thick ascending limb (TAL) of Henle (17,55). After bulk transport in the proximal tubule and TAL, the distal nephron, including renal CNT and CD, is responsible for the final regulation of urinary sodium excretion.…”

Losartan treatment normalizes renal sodium and water handling in rats with mild congestive heart failure

“…The mechanisms behind this impairment in sodium handling in mild CHF are not fully clarified, but it has been suggested that renal sodium retention in mild CHF is caused by an increase in proximal tubular sodium reabsorption (21,36). However, in another study using lithium clearance (C Li ) as a marker for delivery of fluid out of the proximal tubules, Eiskjaer and co-workers (9) showed that proximal tubular function was normal in patients with CHF and increased plasma levels of renin and aldosterone.…”