Does nitric oxide contribute to the negative chronotropic and inotropic effects of endothelin-1 in the heart?
N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, was used to examine whether nitric oxide was involved in the negative chronotropic and inotropic effects of endothelin-1 in the presence of isoprenaline in mammalian heart. In isolated rabbit right atria, endothelin-1 elicited a negative chronotropic effect in the presence of isoprenaline, which was associated with a decrease in the isoprenaline-induced accumulation of cyclic AMP. On the other hand, in the dog ventricular trabeculae, the negative inotropic effect of endothelin-1 was not accompanied by a significant reduction in the isoprenaline-induced accumulation of cyclic AMP. N omega-nitro-L-arginine methyl ester affected neither the negative chronotropic effect nor the negative inotropic effect of endothelin-1. The effects of endothelin-1 on the isoprenaline-induced cyclic AMP accumulation were not influenced by N omega-nitro-L-arginine methyl ester either. These results indicate that the negative chronotropic and inotropic effects of endothelin-1 in the presence of isoprenaline in mammalian cardiac muscle do not involve the nitric oxide-mediated signaling pathway.
Zhu
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Department of Pharmacology, Yamagata University School of Medicine, Japan.
Yang
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HT
Endoh
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D004285:Dogs; D019332:Endothelin-1 / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits
D000318:Adrenergic beta-Agonists; D019332:Endothelin-1; D009569:Nitric Oxide; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase