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

Chaki Y.T. Hart, Eugenia L. Hahn, Donna M. Meyer, John C. Burnett, Margaret M. Redfield

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

β-Adrenergic hyporesponsiveness 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 dobutamine (Dob) were assessed during sequential intracoronary infusion of saline, HS-142-1 (a BNP receptor antagonist), and HS-142-1 + NG-monomethyl-L-arginine (L-NMMA) in anesthetized 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 (%ΔdP/dt) 47 ± 4% saline vs. 54 ± 7% HS-142-1, P = not significant]. Addition of intracoronary L-NMMA to HS-142-1 enhanced the response to Dob (%ΔdP/dt 73 ± 8% L-NMMA + HS-142-1, P < 0.05 vs. H142-1). In normal dogs, intracoronary SNP blunted the inotropic response to Dob (%ΔdP/dt 93 ± 6% saline vs. 71 ± 5% SNP, P < 0.05), whereas intracoronary BNP had no effect. In CHF dogs, the time constant of LV pressure decay during isovolumic relaxation increased with intracoronary HS-142-1 (48 ± 4 ms saline vs. 58 ± 5 ms HS-142-1, P < 0.05) and further increased with intracoronary L-NMMA (56 ± 6 ms HS-142-1 vs. 66 ± 7 ms L-NMMA + HS-142-1, P < 0.05). Endogenous BNP and NO preserve diastolic function in CHF, whereas NO but not BNP inhibits β-adrenergic responsiveness.

Original languageEnglish (US)
Pages (from-to)H146-H154
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number1 50-1
StatePublished - Oct 10 2001

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Keywords

  • Inotropy
  • Lusitropy
  • cGMP

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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