Influence of endothelium on the vasoconstrictor effect of dihydroergotamine in the isolated rat aorta.

The vasoconstrictor effect of dihydroergotamine was studied in endothelium-containing and endothelium-denuded rat aortic rings. The integrity of the endothelium was assessed by the relaxant effect of acetylcholine on precontracted aortic rings, which was absent after removal of endothelium by mechanical rubbing or exposure to saponin. Dihydroergotamine (0.01-10 mumol/l) caused no or only a small contractile effect in the presence of endothelium, while in endothelium-denuded aortic rings a pronounced concentration-dependent increase in tension was observed. The 5-HT antagonist cyproheptadine (2 mumol/l) inhibited the dihydroergotamine-induced vasoconstriction, that means, 5-HT receptors are involved in the vasoconstrictor effect. In the presence of endothelium, the contractile effect of dihydroergotamine was enhanced by the guanylate cyclase inhibitor methylene blue (2 mumol/l) and became comparable in magnitude to that observed in deendothelialized preparations. 8-Bromo-cGMP (50 mumol/l) counteracted the potentiating effect of methylene blue. In the presence of cyproheptadine, methylene blue failed to enhance the dihydroergotamine effect. These results might explain the occurrence of undesired vasospastic effects of dihydroergotamine in arterial vessels with endothelial lesions.