Congestive heart failure (CHF) is characterized by a reduction in cardiac output (C.O). The reduction in C.O activates a series of complex and multifactorial compensatory responses that increase sodium retention and lead to edema formation. Although, the renin angiotensin system appears to play a key role in this regard, the mechanisms underlying these responses are not fully known. We investigated 1) The renal effects of atrial natriuretic peptide (ANP8-33) before and after the induction of CHF by creation of an aortocaval fistula (ACF) in rats; 2) The effects of chronic treatment with losartan, an angiotensin AT-1 receptor antagonist, on sodium excretion and the renal response to ANP in rats with decompensated CHF; and 3) The effects of HOE-140, a bradykinin B2 receptor antagonist, on the renal response to ANP in rats with compensated CHF. In control rats, ANP (10-50microg/kg/h) caused dose dependent increases in urine flow (UV), absolute sodium excretion (UNaV) and urinary excretion of cGMP (UcGMPV). Infusion of the same doses of ANP into rats with compensated CHF induced remarkable natriuresis, diuresis and an increase in UcGMPV, whereas in rats with decompensated CHF the renal responses UcGMPV were markedly blunted. Chronic losartan treatment, resulted in dramatic natriuresis in decompensated rats, but not in compensated and control rats. Furthermore, losartan treatment restored the natriuretic and UcGMPV responses of decompensated rats to ANP. Treatment of the compensated rats with HOE-140 (100 nmol/kg/h) did not affect their renal response to ANP. In addition, infusion of HOE-140 alone into compensated rats had no significant effect on their basal UV or UNaV. These findings indicate that: 1) angiotensin II plays a major role in the development of sodium retention and in the blunted renal response to ANP in CHF and suggest that losartan is good therapy for cardiac edema, and 2) bradykinin dose not modulate the acute renal response to endogenous or exogenous ANP in compensated CHF.
