Reversal of corticosterone-induced supersensitivity of vascular smooth muscle to noradrenaline by arachidonic acid and prostacyclin.
In the isolated perfused hindlimb preparation of rats treated with corticosterone (2 x 20 mg/kg daily for 2 days), the dose-response curve to noradrenaline was shifted to the left, indicating supersensitivity of the vascular bed to noradrenaline. Perfusion with arachidonic acid (10(-5) M) and prostacyclin (10(-9) M) for 5 min reversed the supersensitivity induced by corticosterone. The metabolite of prostacyclin, 6-keto PGF1 alpha(10(-9) M), was ineffective in this respect. In rats which had received desoxycorticosterone acetate (2 x 5 mg/kg daily for 7 days), there was supersensitivity of the hindlimb preparation to noradrenaline similar to that in corticosterone-treated rats. In that case, however, administration of arachidonic acid did not reverse the leftward shift of the dose-response curve. Administration of indomethacin (2 x 2.5 mg/kg for 7 days) prior to the perfusion experiment also resulted in a shift of the noradrenaline dose-response curve to the left, which was less pronounced than the shift induced by corticosterone. Combined administration of corticosterone and indomethacin caused the same increase in noradrenaline sensitivity as did corticosterone alone. Since glucocorticoids inhibit the release of arachidonic acid from phospholipids, it is concluded that corticosterone may enhance the sensitivity to noradrenaline by affecting the biosynthesis of prostaglandins.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D003345:Corticosterone / Q000037:antagonists & inhibitors*; D011464:Epoprostenol / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects
D001095:Arachidonic Acids; D011453:Prostaglandins; D011464:Epoprostenol; D003345:Corticosterone; D009638:Norepinephrine; D007213:Indomethacin