Endothelium-derived contracting factor in carotid artery of hypertensive Dahl rats.
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 micrograms 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.
Zhou
M S
MS
Second Department of Physiology, Kagawa Medical University, Kagawa, Japan.
Nishida
Y
Y
Chen
Q H
QH
Kosaka
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism*; D004351:Drug Resistance; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D012965:Sodium Chloride; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D001643:Bridged Bicyclo Compounds; D016232:Endothelins; D005229:Fatty Acids, Monounsaturated; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; C067427:ONO 8809; D012965:Sodium Chloride; D000109:Acetylcholine