"VASCULAR HYPOREACTIVITY TO ANGIOTENSIN II AND NORADRENALINE IN A RABBIT MODEL OF OBESITY

JEREZ S, SCACCHI F, SIERRA L, KARBINER S, PERAL DE BRUNO M.

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY

LIPPINCOTT WILLIAMS & WILKINS

Año: 2012 vol. 59 p. 49 - 57

0160-2446

The aim of this study was to investigate the vascular reactivity of angiotensin II and noradrenaline and their relationship with endothelial function in a model of obesity in rabbits. Rabbits were fed either a high-fat diet (HFD) or regular chow (CD) for 12 weeks. After 12 weeks, the HFD rabbits showed higher blood pressure, body weight and insulin levels. Glucose tolerance was impaired and positively related to blood pressure. An endothelium-independent decrease of the sensitivity to angiotensin II (pD2 Endothelium-intact aortic rings (E+) in CD: 8.02±0.07 vs. HFD: 7.60±0.01; pD2 Endothelium-removed aortic rings (E-) in CD: 8.16±0.11 vs. HFD: 7.83±0.16) and noradrenaline (pD2 E+ in CD: 6.36±0.06 vs. HFD: 5.29±0.06; pD2 E- in CD: 6.11±0.08 vs HFD: 5.80±0.08) was found. Noradrenaline desensitized the angiotensin II response (pD2 with noradrenaline pretreatment in E+: 7.03±0.16; in E-: 7.10±0.02), but angiotensin II did not modify the noradrenaline response. Acetylcholine maximal relaxation and basal NO release were similar in both diet groups. The endothelium reduced the efficacy to angiotensin II (Rmax CD: 4604±574 mg vs. HFD: 3251±533 mg) and noradrenaline (Rmax CD: 11675±804 mg vs. HFD: 7975±960 mg) treatment. L-NAME recovered the efficacy of noradrenaline (Rmax L-NAME: 12015±317 mg) treatment but had no effect on the angiotensin II. Additionally, noradrenaline increased NO levels, but angiotensin II did not. Therefore, NO was associated with hyporeactivity to noradrenaline. The resting potential was more negative in E+, and the endothelium diminished the angiotensin II-induced depolarization. These findings demonstrated that the cross talk and the endothelium may induce hiporeactivity to angiotensin II and noradrenaline as a mechanism to compensate the increase of the blood pressure in HFD-induced obesity.