Combined effects of endothelin-1 and platelet activating factor on rat aorta vasoconstriction

Abstract

Endothelin (ET-1) is a potent vasoconstrictor derived from endothelial cells. Platelet activating actor (PAF) is a phospholipid mediator synthesized by a variety of cell types. ET-1 and PAF may play important roles in modulating vasomotor tone and blood pressure. Little is known about their combined vasoconstrictive effects. The objective of this study was to investigate the combined effects of ET-1 and PAF on the rat aorta. Thoracic aortic rings of rats were suspended in organ baths and ET-1 (5nM) and PAF (10nM) were added. Contractions of aortic rings were measured by transducers. PAF significantly potentiated and prolonged ET-1 induced vasoconstriction which was endothelium-independent. However, PAF alone did not induce constriction of aortic ring. Indomethacin (cyclooxygenase inhibitor) did not inhibit ET-1 induced vasoconstriction but significantly inhibited PAF potentiated ET-1 induced vasoconstriction. When phosphoramidon (an inhibitor of endothelin converting enzyme) was added to the organ bath, the combined effect of PAF and ET-1 on vasoconstriction was not affected. This result suggests that PAF potentiated vasoconstriction is not due to the synthesis of ET-1. In conclusion, our results demonstrate that PAF potentiated ET-1 induced vasoconstriction may take part in aortic smooth muscle cells via the cyclooxygenase pathway.