INHIBITORY EFFECT OF FENTHION AND DIAZINON ON THE CONTRACTION OF RAT AORTA, AND ITS CONTRIBUTION TO LETHALITY

Fenthion and diazinon, P = S type organothiophosphates which are precursors of cholinesterase inhibitors, cause remarkable atropine-insensitive hypotension in rats when administered intravenously in lethal doses. We investigated their effects on isolated rat aorta and atria to reveal the site of action. Fenthion and diazinon inhibited both types of contractions induced by high K+ solution and norepinephrine in aortic preparations from which the endothelium was removed. IC50 values (under [Ca2+]= 1.5 mM) were 2 x 10(-5) M and 7 x 10(-5) M, respectively. However, the atrial preparations were relatively resistant, since fenthion showed no effect up to 10(-3) M and diazinon at 10(-4) M exhibited a slight inhibition which was antagonized by atropine. The hypotensive effect of fenthion or diazinon was therefore attributable to the direct inhibiting action on the arterial muscle tone, which may be independent of the activation of muscarinic receptors. The results suggested that fenthion and diazinon affect the movement and/or utilization of calcium in the aortic muscle cells, since an increase in the calcium concentration in the bathing solution antagonized their inhibitory effect.