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

The present study is designed to investigate whether acetylcholine (ACh) el icits an endothelium-derived contracting factor (EDCF) and whether it contr ibutes to decreased relaxant response induced by ACh in Dahl rats. Dahl sal t-sensitive (DS) and -resistant (DR) rats were fed a 0.4% NaCl or an 8% NaC l diet for 4 weeks. High sodium intake significantly increased blood pressu re in DS rats but not in DR rats. The carotid rings were suspended for isom etric tension recording. ACh caused an endothelium-dependent contraction in carotid rings from hypertensive DS rats but not from normotensive Dahl rat s. Atropine, indomethacin, SQ29548, or ONO-3708 (prostaglandin H-2 [PGH(2)] /thromboxane A(2) [TXA(2)] receptor antagonist) abolished ACh-induced contr action, and OKY-046 (inhibitor of TXA(2) synthetase) partially attenuated t he contraction. High sodium intake significantly enhanced contraction evoke d by U46619, a PGH(2)/TXA(2) receptor agonist, in both DS and DR rats. In c ontrast, ACh-induced relaxation was significantly depressed in the rings fr om hypertensive DS rats, and ONO-3708 partially improved the depressed rela xation. Administration of ONO-8809 (an orally active PGH(2)/TXA(2) receptor antagonist; 30 mu g per body per day) for 4 weeks neither reduced blood pr essure nor improved the depressed ACh-induced relaxation in hypertensive DS rats. These results suggest that ACh causes release of EDCF in carotid rin gs of hypertensive DS rats, which is likely to be PGH(2) and TXA(2). The ED CF contributed in part to the depressed ACh-induced relaxation.