Does thromboxane A(2) synthase inhibitor UK-38485 prevent the vasoconstrictor effects of endothelin-1 on rabbit basilar artery?

Prevention of the production of thromboxane A(2) -a potent vasoconstrictor and aggregating metabolite of arachidonic acid- or infusion of the stable a nalogues of prostacyclin -which is another cyclooxygenase metabolite of ara chidonic acid- has been shown to be beneficial in cerebral vasoconstriction . Endothelin-l, a peptide derived from endothelial cells, has been shown to induce a long-lasting cerebral vasoconstriction both in vivo and in vitro. The purpose of this study was to investigate the role of a novel thromboxa ne A(2)-synthase inhibitor UK 38485 on the acute vascular and morphological effects of Endothelin-l applied intra-arterially on rabbit basilar arterie s. The inguinal region of twenty four anaesthetized albino rabbits of both sex es were dissected and a catheter was inserted into the aorta via the femora l artery, for control angiography of the basilar artery and intra-arterial injection of ET-1 (0.25 ng total dose) and UK 38485 at a dose of 0.05 mu g kg(-1) min(-1) for 20 min or saline. Angiographic vasoconstriction quantifi cation and morphological investigations of both vessels and brain stem eith er by light microscopy or transmission electron microscopy were the techniq ues applied for the study. We found out that, although the systemic administration of UK 38485 resulte d in a potent antagonism of the acute vasoconstriction as visualized in ang iographic studies, it did not affect the morphological changes induced by E ndothelin-l on the vessel wall. The results indicated that there might have been an interaction between Endothelin-l and the prostaglandin synthesis m echanism in acute cerebral vasoconstriction.