Renal function in high-output heart failure in rats: role of endogenous natriuretic peptides

The physiologic and pathophysiologic importance of natriuretic peptides (NP) has been imperfectly defined. The diminished renal responses to exogenous atrial NP in heart failure have led to the perception that the endogenous NP system might be less effective and thus contribute to renal sodium retention in heart failure. This study tests the hypothesis that in experimental heart failure, the renal responses to an acute volume load are still dependent on the NP system. The specific antagonist HS-142-1 was used to block the effects of NP in a model of high-output heart failure induced by an aortocaval shunt. Plasma cGMP levels and renal cGMP excretion were significantly lower in shunted and sham-operated rats receiving HS-142-1, compared with vehicle-treated controls, indicating effective blockade of guanylate cyclase-coupled receptors. Baseline sodium excretion and urine flow rate were lower in HS-142-1-treated sham-operated rats (15.2+/-1.1 microl/min versus 27.5+/-3.1 microl/min with vehicle, P < 0.001) and in HS-142-1-treated shunted rats (8.1+/-1.3 microl/min versus 19.9+/-2.3 microl/min with vehicle, P < 0.001). After an acute volume load, the diuretic and natriuretic responses were attenuated by HS-142-1 in control and shunted rats. The renal responses were reduced by HS-142-1 to a significantly greater extent in shunted rats than in control rats. HS-142-1 did not induce any significant systemic hemodynamic changes in either group, nor did it alter renal blood flow. However, the GFR in HS-142-1-treated shunted rats was lower than that in vehicle-treated shunted rats, both at baseline (0.6+/-0.3 ml/min versus 2.1+/-0.4 ml/min with vehicle, P < 0.05) and after an acute volume load (1.2+/-0.4 ml/min versus 2.6+/-0.4 ml/min with vehicle, P = 0.01), whereas no such effect was observed in control rats. These data indicate that the maintenance of basal renal function and the responses to acute volume loading are dependent on the NP system. The NP seem to be of particular importance for the maintenance of GFR in this model of experimental heart failure. These observations provide new insights into the importance of the renal NP system in heart failure.