Mechanisms of hypotension in iminoctadine poisoning: pharmacological analysis in rats.
Iminoctadine, a fungicide used widely in fruit culture, causes hypotension in human acute oral poisoning. In an attempt to elucidate this mechanism, we investigated the effects of iminoctadine on the cardiovascular system of rats. In anesthetized rats, intravenously administered iminoctadine produced hypotension and tachycardia. In isolated right atria beating spontaneously in Krebs-Ringer's solution, iminoctadine produced an increase in heart rate. It also produced a positive inotropic response in electrically driven left atria. These responses were partially diminished by atenolol, a beta 1-adrenoceptor antagonist, and also partially diminished to a similar degree in atria of reserpinized rats. Therefore, the positive inotropic and chronotropic effects of iminoctadine were partially mediated via the release of norepinephrine from sympathetic nerve terminals. In aortic ring segments, iminoctadine caused a rightward shift of the concentration-contractile response curve for phenylephrine but did not affect those for prostaglandin F2 alpha or KCl. Iminoctadine produced a potent vasodilation in aortic segments precontracted with phenylephrine. Removal of the aortic endothelium produced a rightward shift of the concentration-response curve for iminoctadine. When the aortic ring preparations were precontracted with prostaglandin F2 alpha or KCl, iminoctadine produced only slight vasodilation. Therefore, the vasodilation caused by iminoctadine is due mostly to its alpha 1-adrenoceptor antagonizing action, and partly to endothelium-dependent mechanisms our data suggest that the hypotension induced by iminoctadine is due to its vasodilator effects.
Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
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Koyama
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Yamashita
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Miyauchi
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Goto
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D005659:Fungicides, Industrial / Q000506:poisoning*; D006146:Guanidines / Q000506:poisoning*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; 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; D009411:Nerve Endings / Q000187:drug effects; D011041:Poisoning / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D005659:Fungicides, Industrial; D006146:Guanidines; D015237:Dinoprost; C012343:guazatine