| 17035095 |
Moroe H, Honda H: Comparison of endothelial function in the carotid artery between normal and short-term hypercholesterolemic rabbits. Comp Biochem Physiol C Toxicol Pharmacol. 2006 Oct;144(2):197-203. Epub 2006 Sep 3.
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. |
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