Effects of renal neutral endopeptidase inhibition on sodium excretion, renal hemodynamics and neurohormonal activation in patients with congestive heart failure

被引:13
作者
Kimmelstiel, CD
Perrone, R
Kilcoyne, L
Souhrada, J
Udelson, J
Smith, J
deBold, A
Griffith, J
Konstam, MA
机构
[1] TUFTS UNIV,NEW ENGLAND MED CTR HOSP,SCH MED,DEPT MED,DIV NEPHROL,BOSTON,MA 02111
[2] PFIZER INC,PFIZER CENT RES,GROTON,CT 06340
[3] UNIV OTTAWA,OTTAWA CIVIC HOSP,INST HEART,OTTAWA,ON,CANADA
关键词
congestive heart failure; atrial natriuretic factor; renal neutral endopeptidase; natriuresis; cGMP;
D O I
10.1159/000177059
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 candoxatril-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.
引用
收藏
页码:46 / 53
页数:8
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