Endothelium-derived contracting factor in carotid artery of hypertensive Dahl rats

Abstract —The present study is designed to investigate whether acetylcholine (ACh) elicits an endothelium-derived contracting factor (EDCF) and whether it contributes to decreased relaxant response induced by ACh in Dahl rats. Dahl salt-sensitive (DS) and -resistant (DR) rats were fed a 0.4% NaCl or an 8% NaCl diet for 4 weeks. High sodium intake significantly increased blood pressure in DS rats but not in DR rats. The carotid rings were suspended for isometric tension recording. ACh caused an endothelium-dependent contraction in carotid rings from hypertensive DS rats but not from normotensive Dahl rats. Atropine, indomethacin, SQ29548, or ONO-3708 (prostaglandin H 2 [PGH 2 ]/thromboxane A 2 [TXA 2 ] receptor antagonist) abolished ACh-induced contraction, and OKY-046 (inhibitor of TXA 2 synthetase) partially attenuated the contraction. High sodium intake significantly enhanced contraction evoked by U46619, a PGH 2 /TXA 2 receptor agonist, in both DS and DR rats. In contrast, ACh-induced relaxation was significantly depressed in the rings from hypertensive DS rats, and ONO-3708 partially improved the depressed relaxation. Administration of ONO-8809 (an orally active PGH 2 /TXA 2 receptor antagonist; 30 μg per body per day) for 4 weeks neither reduced blood pressure nor improved the depressed ACh-induced relaxation in hypertensive DS rats. These results suggest that ACh causes release of EDCF in carotid rings of hypertensive DS rats, which is likely to be PGH 2 and TXA 2 . The EDCF contributed in part to the depressed ACh-induced relaxation.