title: Characterization of endothelium-dependent relaxation and modulation by treatment with pioglitazone in the hypercholesterolemic rabbit renal artery.
abstract: The present study was undertaken to investigate vascular function in hypercholesterolemic rabbits and also to characterize the effects of pioglitazone on it. Rabbits were fed normal, 0.5% cholesterol chow, or 0.5% cholesterol chow plus 300 ppm pioglitazone for 5 or 10 weeks. The tension of isolated renal artery rings was measured isometrically, and morphometric analysis was performed. The cholesterol chow diet administered for 5 weeks did not affect acetylcholine-induced relaxation in the renal artery but that for 10 weeks decreased it. The N(G)-nitro-L-arginine (L-NOARG)- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine in the renal artery was enhanced in rabbits receiving the cholesterol chow for 5 or 10 weeks, as compared to rabbits receiving the control diet, and the percentage of plaque area formation was increased in the renal artery by the cholesterol chow for 10 weeks. Pioglitazone normalized them without lowering serum lipid levels. The resistant parts of acetylcholine-induced relaxation was significantly inhibited when the renal artery was treated with charybdotoxin, an inhibitor of large and intermediate conductance Ca(2+)-activated K(+) channels, or N,N-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a cytochrome P-450 monooxygenase inhibitor. Results indicate that hypercholesterolemia enhances endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in the rabbit renal artery and pioglitazon normalizes it without lowering serum lipid levels, and suggest that the maintenance of endothelial function by pioglitazon is related to the mechanisms for its anti-atheromatous activity.
authors.affiliation: Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Moroe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujii
authors.forename: Hideo
authors.initials: H
authors.lastname: Honda
authors.forename: Katsunori
authors.initials: K
authors.lastname: Arai
authors.forename: Masao
authors.initials: M
authors.lastname: Kanazawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Notoya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kogo
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D000077205:Pioglitazone; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects* / Q000503:physiopathology; D019789:Tetraethylammonium / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D045162:Thiazolidinediones; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D019335:Nitroarginine; D019789:Tetraethylammonium; D011335:Proadifen; D000077205:Pioglitazone; D007213:Indomethacin