Differential effects of natriuretic peptides and NO on LV function in heart failure and normal dogs

ential effects of natriuretic peptides and NO on LV function in heart failure and normal dogs. Am J Physiol Heart Circ Physiol 281: H146–H154, 2001.—b-Adrenergic hyporespon-siveness in congestive heart failure (CHF) is mediated, in part, by nitric oxide (NO). NO and brain natriuretic peptide (BNP) share cGMP as a second messenger. Left ventricular (LV) function and inotropic response to intravenous dobut-amine (Dob) were assessed during sequential intracoronary infusion of saline, HS-142-1 (a BNP receptor antagonist), and HS-142-1 1 NG-monomethyl-L-arginine (L-NMMA) in anes-thetized dogs with CHF due to rapid pacing and in normal dogs during intracoronary infusion of saline, exogenous BNP, and sodium nitroprusside (SNP). In CHF dogs, intracoronary HS-142-1 did not alter the inotropic response to Dob [percent change in first derivative of LV pressure (%DdP/dt) 47 6 4% saline vs. 54 6 7 % HS-142-1, P 5 not significant]. Addition of intracoronary L-NMMA to HS-142-1 enhanced the respons