Role of nitric oxide in cardiac beta-adrenoceptor-inotropic response.
We examined some of the signalling events in the negative modulation of isoproterenol-induced stimulation of contractility in rat isolated atria. Isoproterenol-mediated positive inotropic response is accompanied by the stimulation of nitric oxide synthase (NOS) and an increase in the production of cyclic GMP (cGMP). Inhibition of NOS and guanylate cyclase increased the dose-response curve of isoproterenol on contractility. Inhibitors of calcium flux or calcium calmodulin, but not of protein kinase C, abrogated these mechanisms. The existence of a modulatory negative inotropic-cyclic GMP-mediated mechanism limiting the effect of beta-adrenergic stimulation in myocardium is discussed.
Sterin-Borda
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Centro de Estudios Farmacológicos y Bótanicos, Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina, Buenos Aires, Argentina.
Genaro
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A
Perez Leiros
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C
Cremaschi
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G
Vila Echagüe
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A
Borda
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D000818:Animals; D016275:Atrial Function; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis; D006325:Heart Atria / Q000201:enzymology; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical
D002316:Cardiotonic Agents; D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D006152:Cyclic GMP; D007545:Isoproterenol