The present experiment was performed to identify endothelium-derived contracting factor produced by acetylcholine stimulation in the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The rings of the thoracic aorta were obtained from age-matched SHR and WKY rats, and changes in isometric tension were recorded. The relaxant responses to acetylcholine in the aortic rings from SHR were significantly weaker than those from WKY rats. The relaxant responses to acetylcholine were significantly enhanced by pretreatment with a cyclooxygenase inhibitor (indomethacin) or thromboxane A 2 / prostaglandin H 2 receptor antagonist (ONO-3708) in aortic rings from both SHR and WKY rats. A thromboxane A 2 synthetase inhibitor (OKY-046) did not affect the acetylcholineinduced relaxation in the aortic rings from SHR or WKY rats. In the organ bath solution, after acetylcholine stimulation, prostaglandin E 2 and 6-keto-prostaglandin F la concentrations increased but not prostaglandin F 2a and thromboxane B 2 concentrations. Exogenous prostaglandin H 2 , a stable analogue of thromboxane A 2 , and prostaglandin F 2a induced contractions of the SHR rings at a lower concentration than prostaglandin E 2 , prostaglandin D 2 , and prostaglandin I 2 . These contractile responses to various prostaglandins were markedly inhibited by pretreatment with ONO-3708. A prostacyclin synthetase inhibitor did not affect the relaxant responses to acetylcholine in the SHR rings. These results show that endotheliumderived contracting factor is produced and released by acetylcholine stimulation not only in the aorta of SHR but also in those of WKY rats and suggest that prostaglandin H 2 , a precursor of the released prostaglandins, is a strong candidate for endothelium-derived contracting factor produced by acetylcholine stimulation. (Hypertension 1990;15:475-481) A ll blood vessels are lined by the endothelium, and the important role of an organic or functional abnormality of endothelial cells in the pathogenesis and pathophysiology of various diseases has attracted attention.In 1980, Furchgott et al 1 found that acetylcholine induced endothelium-dependent relaxation in the rabbit aorta. Since then, various substances have been reported to induce endothelium-dependent relaxation in most of the blood vessels in mammals. 23Several pharmacological observations have strongly suggested that there is more than one endothelium-

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