La inhibición de la síntesis de 20-HETE mejora la función endotelial y disminuye la reactividad vascular en arterias de conejos hipercolesterolémicos.

SCACCHI FABRICIO; SIERRA LILIANA; GUERRERO RAMIRO; PERAL DE BRUNO MARÍA; JEREZ SUSANA

Tafí del valle - Tucumán

Jornada; XXV Jornadas Científicas de la Asociación de Biología de Tucumán.; 2008

Asociación de Biología de Tucumán

The aim of this work was to study the effect of a CYP4A2-specific inhibitor in endothelial function and vascular reactivity to angiotensin II (AngII) in hypercholesterolemic and controls rabbits. Rabbits were feed with either normal rabbit chow (CD) or a diet cointaining 1% cholesterol for 6 weeks (HD). PAM, CT, LDL, HDL and TG were measured. Thoracic aorta was excised. Rings were cut and mounted in an organ bath to register isometric contractions. CAY10434 10-6 M (omega hydroxylase specific inhibitor) was added or not (control) 30 min. before stimulation with noradrenaline 5x10-6 M and cumulative dose response curve (CDRC) to Acetylcholine (Ach). After washing, one CDRC to Ang II was performed. Griess-technique was used to measure Nitrites-release in presence or absence of CAY10434. Results: CT and LDL were higher in HD. HD impairs Ach relaxation and improves Ang II-response. These effects were blocked by CAY10434. Furthermore, NO- basal release was higher in DC.  CAY10434 improves NO-release in DC and normalize NO-release in DH. Conclusions: In phisiology conditions NO would inhibit CYP4A2 and 20-HETE-production is counterbalanced. In hypercholesterolemia, vascular dysfunction induced by NO-deficit would improve 20-HETE-release. This metabolite would sensitize vessel to Ang II response.