INVESTIGADORES
JEREZ Susana Josefina
artículos
Título:
Hypercholesterolemia modifies angiotensin II desensitisation and cross talk between 1-adrenoceptor and angiotensin AT1 receptor in rabbit aorta.
Autor/es:
SUSANA JEREZ; LILIANA SIERRA; FABRICIO SCACCHI; MAR√ćA PERAL DE BRUNO
Revista:
EUROPEAN JOURNAL OF PHARMACOLOGY
Editorial:
Elsevier
Referencias:
Lugar: Netherlands; Año: 2010 vol. 635 p. 149 - 155
ISSN:
0014-2999
Resumen:
This study characterised the effect of a hypercholesterolemic diet on the interactions of hormone receptors in the rabbit aorta, both in homologous desensitisation to angiotensin II and cross talk between alfa 1-adrenoceptors and angiotensin AT1receptors. Rabbits were fed either a normal chow or a diet containing 1% cholesterol for 6-7-weeks. Isometric contractions were measured in endothelium-intact or endothelium-removed aortic rings from control and hypercholesterolemic rabbits. Concentration response curves to angiotensin II or noradrenaline incubated with or without prazosin or losartan were performed. In another group, the resting potential was recorded at baseline and following angiotensin II or noradrenaline stimulation. Rabbits fed a hypercholesterolemic diet showed higher plasma levels of total cholesterol and LDL-cholesterol and impaired relaxation to acetylcholine. Homologous desensitisation to angiotensin II was found in endothelium-intact but not in endothelium-removed arteries. Cross talk between alfa1-adrenoceptors and angiotensin AT1 receptors was modified with respect to physiological conditions. In control rabbits, angiotensin II desensitised the noradrenaline response but noradrenaline did not modify the angiotensin II-response. However, in hypercholesterolemic rabbits, angiotensin II sensitised the noradrenaline-response and noradrenaline desensitised the angiotensin II-response. Furthermore, the resting potential remains hyperpolarised after noradrenaline stimulation in hypercholesterolemic rabbits. Modifications in homologous desensitisation to angiotensin II and cross talk between alfa1-adrenoceptors and angiotensin AT1 receptors suggest that hypercholesterolemia induces early tissue dysfunction by altering endothelial and smooth muscle cell regulatory properties. This may be one of the mechanisms by which hypercholesterolemia could be involved in the onset and progression of chronic vascular diseases such as hypertension and arteriosclerosis.