Comparison of endothelial function in the carotid artery between normal and short-term hypercholesterolemic rabbits.
The present study was undertaken to investigate and compare the vascular function in carotid arteries isolated from normal short-term hypercholesterolemic rabbits. Rabbits were fed normal or 0.5% cholesterol chow for 5 weeks. The tension of isolated carotid artery rings was measured isometrically. Serum lipid levels were measured and morphometric analysis was performed. And content of nitrate/nitrite in the carotid artery was also determined. In the carotid artery precontracted by phenylephrine, the cholesterol chow diet administered for 5 weeks decreased acetylcholine-induced relaxation at only middle concentrations, though it significantly increased the content of nitrate/nitrite, the sum of stable nitric oxide metabolites, in the carotid artery. Cholesterol chow for 5 weeks had no influence on sodium nitroprusside-induced relaxation in the carotid artery. The N(G)-nitro-L-arginine- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine was significantly decreased in rabbits receiving the cholesterol chow as compared to rabbits receiving the control diet. The resistant part of acetylcholine-induced relaxation was significantly inhibited when the carotid artery was treated with glibenclamide, a selective inhibitor of ATP-sensitive K(+) channels, 4-aminopyridine, an inhibitor of voltage-dependent K(+) channels, or charybdotoxin, an inhibitor of large and intermediate conductance Ca(2+)-activated K(+) channels, and it was significantly inhibited by tetraethylammonium, a non-selective inhibitor of Ca(2+)-activated K(+) channels and N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a nonselective cytochrome P-450 monooxygenase (CYP) inhibitor, or ketoconazole, a selective CYP3A inhibitor in only normal rabbits. These results suggest that short-term hypercholesterolemia decreased EDHF-induced relaxation mediated through K(+) channels in rabbit carotid artery and that it may be due partially to the inhibition of CYP3A system in the carotid artery at an early stage of hypercholesterolemia.
Moroe
Hiroko
H
Second Department of Physiology, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo, 142-8555, Japan.
Honda
Hideo
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects
D001685:Biological Factors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D000109:Acetylcholine; D007213:Indomethacin