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      Effects of Renal Neutral Endopeptidase Inhibition on Sodium Excretion, Renal Hemodynamics and Neuro-hormonal Activation in Patients with Congestive Heart Failure

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          We investigated the effects of inhibiting endogenous atrial natriuretic factor (ANF) metabolism on renal hemodynamics, sodium excretion and neurohormones in 12 patients with New York Heart Association functional class II congestive heart failure (CHF) due to left ventricular systolic dysfunction. In a randomized, placebo-controlled, double-blinded fashion, 8 patients received a single oral dose of candoxatril, an inhibitor of renal neutral endopeptidase, and 4 patients received placebo. Candoxatril treatment increased plasma ANF by 70 ± 71 pg/ml (p < 0.015 vs. placebo) and plasma cGMP by 7.9 ± 2.7 pmol/ml (p < 0.001 vs. placebo), with maximal effects at 3.5 h. Urinary cGMP more than doubled (p = 0.025 vs. placebo). Candoxatril increased urinary sodium by 2.7 ± 2.0 mEq/h (p < 0.05 vs. placebo) and significantly elevated filtration fraction with no significant effect on glomerular filtration rate, renal plasma flow or lithium clearance. A significant reduction in aldosterone concentration with a similar trend in plasma renin activity was noted in can-doxatril-treated patients. Thus in patients with moderate heart failure, renal neutral endopeptidase inhibition increases urinary sodium excretion. The lack of an effect on renal hemodynamics suggests that this natriuresis results from ANF-mediated inhibition of tubular sodium reabsorption. These findings justify additional investigation into potential clinical benefit of endopeptidase inhibition in patients with CHF.

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          Author and article information

          S. Karger AG
          19 November 2008
          : 87
          : 1
          : 46-53
          Department of Medicine, Divisions of aCardiology and bNephrology, Tufts University School of Medicine, New England Medical Center Hospital, Boston, Mass., cPfizer Central Research, Groton, Conn., USA; dUniversity of Ottawa Heart Institute, Ottawa Civic Hospital, Ottawa, Ont., Canada
          177059 Cardiology 1996;87:46–53
          © 1996 S. Karger AG, Basel

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          Page count
          Pages: 8
          Clinical Pharmacology


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