Pharmacological analysis of the positive inotropic effect of endothelin-1 in guinea pig left atria.
Endothelin-1 (ET-1) increased the force of contraction and stimulated phosphoinositide hydrolysis in guinea pig left atria. ET-1 at 20 nM produced a dual-component positive inotropic effect composed of an initial increasing phase (early component) and a second and late developing, greater positive inotropic phase (late component). The late component was preferentially and markedly inhibited by nifedipine and the protein kinase C inhibitors H-7 and staurosporine. In guinea pig left atria, the activation of protein kinase C might contribute to the establishment of the positive inotropic effect of ET-1 mediated by modulation of voltage-dependent Ca2+ channels.
Hattori
Y
Y
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Nakaya
H
H
Endou
M
M
Kanno
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D019311:Staurosporine; D013268:Stimulation, Chemical
D000470:Alkaloids; D016232:Endothelins; D007546:Isoquinolines; D010716:Phosphatidylinositols; D010879:Piperazines; D007294:Inositol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019311:Staurosporine; D009543:Nifedipine