RENAL EFFECTS OF HIGH-DOSE NATRIURETIC PEPTIDE RECEPTOR BLOCKADE IN RATS WITH CONGESTIVE-HEART-FAILURE

Previous studies suggest that elevated plasma atrial natriuretic pepti de (ANP) levels participate in regulating renal excretory function in rats with congestive heart failure (CHF). To define the role of natriu retic peptides (NPs) in the regulation of renal function in CHF, the r enal responses to HS-142-1 (HS), a potent NP receptor antagonist, were studied in anesthetized rats subjected to coronary ligation that deve loped Left ventricular infarction and CHF or in sham-operated (SO) con trol rats. Plasma ANP levels averaged >14-fold higher in rats with CHF than in SO rats. In response to HS (20 mg/kg IV bolus), both mean art erial pressure and renal vascular resistance increased in rats with CH F but not in SO rats; glomerular filtration rate (GFR, 1.26+/-0.04 ver sus 0.76+/-0.11 ml/min) and renal plasma flow rate (RPF, 3.52+/-0.27 v ersus 2.70+/-0.32 mL/min) were significantly reduced in rats with CHF: and in SO rats, GFR (1.26+/-0.06 versus 1.20+/-0.07 mL/min) and RPF ( 3.98+/-0.21 versus 3.99+/-0.18 mL/min) were not significantly affected by HS. The sodium excretion rate (0.18+/-0.04 to 0.06+/-0.01 mu Eq/mi n) and fractional sodium excretion (0.01+/-0.02% to 0.04+/-0.01%) also fell markedly after HS administration in rats with CHF, but these par ameters were unchanged in SO rats. These data indicate that NPs play a critical role in maintaining renal hemodynamic function and inhibitin g tubule sodium reabsorption in rats with CHF, thus opposing sodium re tention and preserving sodium balance in this model.