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 reten tion in heart failure. This study tests the hypothesis that in experimental heart failure. the renal responses to an acute volume load are still depen dent on the NP system. The specific antagonist HS-142-1 was used to block t he effects of NP in a model of high-output heart failure induced by an aort ocaval shunt, plasma cGMP levels and renal cGMP excretion were significantl y lower in shunted and sham-operated rats receiving HS-142-1, compared with vehicle-treated controls. indicating effective blockade of guanylate cycla se-coupled receptors. Baseline sodium excretion and urine flow rate were lo wer in HS-142-1-treated sham-operated rats (15.2 +/- 1.1 mu l/min versus 27 .5 +/- 3.1 mu l/min with vehicle, P < 0.001) and in HS-142-1-treated shunte d rats (8.1 +/- 1.3 mu l/min versus 19.9 +/- 2.3 mu l/min with vehicle, P < 0.001). After an acute volume lend? the diuretic and natriuretic responses were attenuated by HS-142-1 in control and shunted rats. The renal respons es were reduced by HS-142-1 to a significantly greater extent in shunted mt s than in control rats. HS-142-1 did not induce MY significant systemic hem odynamic changes in either group, nor did it alter renal blood flow. Howeve r, the GFR in HS-142-1-treated shunted rats was lower than that in vehicle- treated shunted ruts, 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 suc h effect was observed in control mts. These data indicate that the maintena nce of basal renal function and the responses to acute volume loading are d ependent on the NP system, The NP seem to be of particular importance for t he maintenance of GFR in this modal of experimental heart failure. These ob servations provide new insights into the importance of the renal NP system in heart failure.