Comparison of endothelium-dependent relaxation in carotid arteries from Japanese white and Watanabe heritable hyperlipidemic rabbits

Modifications by atherosclerosis of endothelium-dependent and -independent relaxations were evaluated in carotid arteries isolated from Watanabe herit able hyperlipidemic (WHHL; age 20-29 months) and age-matched Japanese white (JW) rabbits, Marked, patchy atherosclerotic lesions were observed in all WHHL rabbit arteries. Endothelium-dependent relaxations induced by acetylch oline, partly depressed by N-G-nitro-L-arginine (L-NA), were significantly inhibited in the WHHL rabbit arteries with atherosclerosis, compared with t hose in the arteries without atherosclerotic lesions from JW and WHHL rabbi ts. No difference was observed in the relaxation caused by superoxide dismu tase in these arteries. Conversely, endothelium-dependent relaxations by su bstance P were greater in the arteries with and without atherosclerosis fro m WHHL rabbits than in the arteries from JW rabbits. Endothelium-independen t relaxations elicited by sodium nitroprusside and 2,2-(hydroxynitrosohydra zino)bis-ethanamine (NOC18) did not differ in the arteries from JW and WHHL rabbits. The responses to acetylcholine and substance P of JW rabbit arter ies with the endothelium were not attenuated by treatment with pertussis to xin. L-NA-resistant, endothelium-dependent relaxations by substance P were almost abolished by charybdotoxin, and atherosclerosis did not alter the re sponse. It is concluded that endothelial functions, evaluated by substance P, in rabbit carotid arteries are not impaired by atherosclerosis and by lo ng exposure to hyperlipidemia in vivo. Dysfunction of muscarinic receptors may be involved in the depressed response to acetylcholine. As far as the a rteries used in the present study are concerned, responses mediated possibl y by endothelium-derived hyperpolarizing factor (EDHF) are unlikely to be m odulated by atherosclerosis.