JEREZ Susana Josefina
congresos y reuniones científicas
Endothelial dysfunction in hypercholesterolemia induces release of vasoconstrictor arachidonic acid metabolites.
SIERRA L.,; GUERRERO R.,; PERAL DE BRUNO; JEREZ S.
Congreso; MXXXVIII Reunión Anual de la Asociación Argentina de Farmacología Experimental.; 2006
Asociación Argentina de Farmacología Experimental.
Endothelial dysfunction in hypercholesterolemia induces release of vasoconstrictor arachidonic acid metabolites.The aim of this work was to study the influence of arachidonic acid metabolites on the endothelial dysfunction observed in aorta of hypercholesterolemic rabbits. Rabbits were feed with either normal rabbit chow (CD) or a diet cointaining 1% cholesterol for 6 weeks (HD). Thoracic aorta was excised. Rings were cut and mounted in a organ bath to measure NO basal production with Griess reagent and to register isometric contractions. Aortic rings were contracted with noradrenaline and then exposed to increasing doses of acetylcholine (Ach) or sodium nitroprusside (NP) to construct one cumulative dose-response curve (CDRC) in absence or presence of indomethacin or tempol. After washing ,indomethacin or 17-ODYA was added 30 min before one CDRC to angiotensin II (Ang II). Transmembrane potential (Pm) was recorded before and after 10 min of Ang II stimulation in absence or presence of indomethacin or 17-ODYA.Results: relaxations induced by Ach were lower in HC rabbits. This effect was blocked by indomethacin but not tempol. NP-relaxations were the same in all cases. NO-release was lower in HD rabbits. The Ang II reactivity-improvement was abolished by indomethacin and 17-ODYA. Ang II stimulation induced depolarization in HD rabbit aorta. This effect was reversed by 17-ODYA but not indomethacin. These results demonstrate that high cholesterol diet would diminish NO production and would increase the release of vasoconstrictor arachidonic acid metabolites that sensitize smooth muscle to Ang II through increasing 20-HETE synthesis.