Endothelial dysfunction and improvement of the angiotensin II-reactivity in hypercholesterolemic rabbits: role of cyclooxygenase metabolites.

摘要: Abstract The aim of this paper was to study the effect high cholesterol diet on endothelial function and vascular reactivity angiotensin II test role vasoconstrictor cyclooxygenase metabolites in experimental condition. Rabbits were fed with either normal chow or a containing 1% for 6–7-week. Isometric contractions measured rubbed unrubbed aortic rings. Arteries contracted noradrenaline then exposed one cumulative dose–response curve acetylcholine absence (control) presence indomethacin, ( N -[2-cyvlohexyloxy)-4-nitrophenyl]-methanesulfonamide) (NS 398) 4-hydroxy-2,2,6,6-tetraethylpiperidine- -oxyl (tempol). After washing arteries, constructed NS 398, [1 S -[1 alpha,2 beta (5 Z ),3 beta,4 alpha]-7-[3-[[2-[(phenylamino) carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1] hept-2-yl]-5-heptenoic acid (SQ29548) 17-octadecynoic (17-ODYA). In other group, resting potential recorded basal II-stimulated conditions. Indomethacin, 398 17-ODYA added bath before II-stimulation. enriched showed higher plasma levels total LDL. Hypercholesterolemic impaired relaxation. Indomethacin normalized endothelium-dependent relaxation whereas tempol had no phenomenon. Angiotensin II-reactivity increased endothelium intact hypercholesterolemic rings SQ29548 blocked effect. arteries significantly less negative control after but not indomethacin prevented II-depolarization. High caused dysfunction II-reactivity. Both effects cyclooxygenase1-dependent. Deficit NO-production might improve 20-hydroxyeicosatrienoic availability, which induces depolarization II-sensitization. addition, would be metabolized by cyclooxygenase1 20-endoperoxides act through thromboxane A 2 /prostaglandin H receptors contributing increase.