title: Physiological concentration of nitric oxide induces positive inotropic effects through cGMP pathway in isolated rat ventricular myocytes.
abstract: We used authentic NO or NO from NO donors to show that the physiological levels of NO (<1 microM) induce a positive inotropic effect and demonstrated that the effect is evoked through a cGMP-dependent pathway. In isolated rat ventricular myocytes, authentic NO at 588 nM increased both cell shortening and the intracellular Ca(2+) ([Ca(2+)]i) transient (133 and 117%, respectively; p < 0.05 vs. baseline), and 0.16-1.7 microM NO elicited reproducible dose-dependent increases in cell shortening. NOC18 (0.1 mM: actual NO concentration 673 nM) or SNAP (0.1 mM: actual NO concentration 285 nM) showed similar effects (shortening 215% and [Ca(2+)]i transient 160% increases, and shortening 148% and [Ca(2+)]i transient 117% increases, respectively). The NO-induced increases in cell shortening and the [Ca(2+)]i transient were inhibited by an inhibitor of soluble guanylate cyclase (ODQ, 30 microM) or by an inhibitor of cAMP-dependent protein kinase (KT5720, 0.1 microM). In the presence of an inhibitor of cGMP-inhibited cAMP-phosphodiesterase (milrinone, 10 microM), NO failed to increase both cell shortening and the [Ca(2+)]i transient. These results suggest that physiological levels of NO induce positive inotropy through a cGMP-dependent pathway.
authors.affiliation: Department of Physiology, School of Medicine, Tokai University, Isehara, 259-1193, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hirota
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.forename: C
authors.initials: C
authors.lastname: Genka
authors.forename: R
authors.initials: R
authors.lastname: Obama
authors.forename: S
authors.initials: S
authors.lastname: Matsuyama
authors.forename: H
authors.initials: H
authors.lastname: Nakazawa
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology*; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function
chemical_list: D009569:Nitric Oxide; D017868:Cyclic AMP-Dependent Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006152:Cyclic GMP