title: Nitric oxide reduces myocardial contractility in isoproterenol-stimulated rat hearts by a mechanism independent of cyclic GMP or cyclic AMP.
abstract: Nitric oxide has been shown to decrease myocardial contractility and O2 consumption. This study was designed to evaluate the hypothesis that nitric oxide-mediated increases in cyclic GMP require elevated cyclic AMP to produce cardiac depression. Using isolated, Langendorff-perfused rat hearts, we determined the effects of intracoronary nitroprusside (NP, 1 and 10 mM) in the absence and presence of isoproterenol (ISO, 10(-8) M) on cardiac function, O2 consumption, cyclic GMP and cyclic AMP. ISO, with and without NP, increased cyclic AMP (from 287 +/- 21 to 477 +/- 33 pmol/g) without altering cyclic GMP. Left-ventricular pressure increased from 97 +/- 12 to 178 +/- 9 mm Hg and dP/dtmax from 1,786 +/- 275 to 4,049 +/- 354 mm Hg/s. NP increased cyclic GMP (from 4 to 30 pmol/g) in both the absence and presence of ISO, but NP did not alter cyclic AMP. Without ISO, NP insignificantly altered left-ventricular pressure; however, in the presence of ISO, NP significantly decreased left-ventricular pressure by -25 +/- 4 mm Hg and decreased dP/dtmax by -619 +/- 142 mm Hg/s. Isoproterenol increased O2 consumption, but the changes with NP were not significant. When this study was repeated in the presence of LY83583, a guanylate cyclase inhibitor, NP still produced cardiac depression in the presence of ISO. Therefore, cardiodepressant effects of NP were only observed against a background of inotropic stimulation with ISO. However, effects of NP on contractility were unrelated to increases in cyclic GMP or cyclic GMP-induced changes in cyclic AMP.
authors.affiliation: Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA. hweiss@umdnj.edu
authors.forename: H R
authors.initials: HR
authors.lastname: Weiss
authors.forename: J D
authors.initials: JD
authors.lastname: Sadoff
authors.forename: P M
authors.initials: PM
authors.lastname: Scholz
authors.forename: R E
authors.initials: RE
authors.lastname: Klabunde
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000634:Aminoquinolines; D009599:Nitroprusside; D009569:Nitric Oxide; C041715:6-anilino-5,8-quinolinedione; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol