Guanylate cyclase inhibition reduces contractility and decreases cardiac cGMP and cAMP in rat hearts

Richard E. Klabunde, Connie Daloisio, James Tse, Harvey R. Weiss

Research output: Contribution to journalArticle

Abstract

Inhibition of constitutively formed nitric oxide (NO) has been shown to decrease myocardial contractility or enhance it. In either case, a decrease in cGMP has been proposed to explain these opposite effects. This study was designed to evaluate further the hypothesis that basal levels of cGMP are cardiostimulatory, and therefore inhibition of guanylate cyclase should decrease contractility and decrease cGMP. Using paced, constant flow, Langendorff-perfused rat hearts, we determined the effects of intracoronary infusions of the guanylate cyclase inhibitor, LY83583 (LY; 10-5 M), in the absence and presence of isoproterenol (ISO), on cardiac function and ventricular content of cGMP and cAMP. LY, infused for 25 min, decreased left ventricular developed pressure (LVDP) by 44±3 (SE), 77±20 and 120±38 mmHg, in control, 10-9 M, and 10-8 M ISO-stimulated hearts, respectively. ISO increased cAMP without changing cGMP. LY decreased cGMP by about 25% at all levels of ISO, but cAMP decreased by 22% only in the 10-8 M ISO-stimulated group. Therefore, the magnitude of cardiac depression caused by guanylate cyclase inhibition using LY83583 was not correlated with the measured decreases in cGMP or cAMP.

Original languageEnglish (US)
Pages (from-to)A324
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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