INVESTIGADORES
JEREZ Susana Josefina
artículos
Título:
Endothelial dysfunction and improvement of the angiotensin II reactivity in hypercholesterolemic rabbit: role of cyclooxygenase metabolites
Autor/es:
JEREZ SUSANA; SIERRA LILIANA; COVIELLO ALFREDO; PERAL DE BRUNO MAR√ćA
Revista:
EUROPEAN JOURNAL OF PHARMACOLOGY
Editorial:
Elsevier
Referencias:
Lugar: Netherlands; Año: 2008 vol. 580 p. 182 - 189
ISSN:
0014-2999
Resumen:
The aim of this paper was to study the effect of high cholesterol diet on endothelial function and vascular reactivity to angiotensin II and to test the role of vasoconstrictor cyclooxygenase metabolites in this experimental condition. Rabbits were fed with either normal chow or a diet containing 1% cholesterol for 6-7-week. Isometric contractions were measured in rubbed or unrubbed aortic rings. Arteries were contracted with noradrenaline and then exposed to one cumulative dose response curve to acetylcholine in absence (control) or in presence of indomethacin, (N-[2-cyvlohexyloxy)-4-nitrophenyl]-methanesulfonamide) (NS398) or 4-hydroxy-2,2,6,6-tetraethylpiperidine-N-oxyl (tempol). After washing the arteries, one cumulative dose response curve to angiotensin II was constructed in absence or presence of indomethacin, NS398, [1S-[1 alpha,2 beta (5Z),3 beta,4 alpha]-7-[3-[[2- [(phenylamino) carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1] hept-2- yl]-5-heptenoic acid (SQ29548) or 17-octadecynoic acid (17-ODYA). In other group, resting potential was recorded in basal and angiotensin II-stimulated conditions. Indomethacin, NS398 or 17-ODYA were added to the bath before angiotensin II stimulation. Rabbits fed on a diet enriched with cholesterol showed higher plasma levels of total cholesterol and LDL. Hypercholesterolemic diet impaired acetylcholine relaxation. Indomethacin normalized endothelium-dependent relaxation whereas NS398 and tempol had no effect on this phenomenon. Angiotensin II reactivity was increased in endothelium-intact hypercholesterolemic aortic rings and indomethacin, SQ 29548 or 17-ODYA blocked this effect. The resting potential of unrubbed hypercholesterolemic arteries was significantly less negative to control after angiotensin II stimulation. 17-ODYA but not indomethacin prevented angiotensin II-depolarization. High cholesterol diet caused endothelial dysfunction and increased the angiotensin II-reactivity. Both effects were cyclooxygenase1-dependent. Deficit in the NO-production might improve 20-hydroxyeicosatrienoic acid availability, which induces depolarization and angiotensin II-sensitization. In addition, 20-hydroxyeicosatrienoic acid would be metabolized by cyclooxygenase1 to 20-endoperoxides which act through thromboxane A2/prostaglandin H2 receptors contributing to angiotensin II-reactivity increase.