Positive inotropic and negative chronotropic effects of (-)-cis-diltiazem in rat isolated atria.
1. The cardiovascular effects of (-)-cis-diltiazem, an optical isomer of diltiazem, were studied in the isolated atrium and aortic strip. (-)-cis-Diltiazem (30 microM or more) increased the developed tension of the rat left atrium, while (+)-cis-diltiazem (1 microM or more) decreased it. 2. (-)-cis-Diltiazem (1 to 100 microM) decreased the rate of spontaneous beating in the right atrium as did (+)-cis-diltiazem. 3. The potency of the positive inotropic action of (-)-cis-diltiazem was almost the same as that of ouabain in the rat left atrium, but in the guinea-pig left atrium it was considerably weaker than that of ouabain. 4. In both endothelium-intact and endothelium-denuded aortic strips, (-)-cis-diltiazem relaxed the Ca(2+)-induced contraction. In the endothelium-intact rat aortic strip depolarized by 15 mM KCl, Bay K 8644, a calcium channel agonist, increased the contractile force, whereas (-)-cis-diltiazem did not. 5. These results indicate that (-)-cis-diltiazem has a positive inotropic action in isolated atria in rats and guinea-pigs, but the mode of positive inotropic action of (-)-cis-diltiazem is different from that of ouabain or Bay K 8644.
Nasa
Y
Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Ichihara
K
K
Yoshida
R
R
Abiko
Y
Y
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001262:Atenolol / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D014700:Verapamil / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D001262:Atenolol; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C018176:bunazosin; D014700:Verapamil; D004110:Diltiazem; D002118:Calcium