Mechanisms of hypotension in iminoctadine poisoning: pharmacological analysis in rats

Abstract

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 being 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 β 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 F 2α 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 F 2α or KCl, iminoctadine produced only slight vasodilation. Therefore, the vasodilation caused by iminoctadine is due mostly to its α 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.