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.