MECHANISMS CONTRIBUTING TO ANGIOTENSIN-II REGULATION OF BODY-WEIGHT

Previous studies in our laboratory have implicated adipose tissue as a potential site for local angiotensin II(ANG II) synthesis. However, f unctions of ANG II in adipose tissue and the impact of ANG II on body weight regulation are not well defined. To study the effect of ANG II on body weight, a chronic ANG II infusion model was used. In study 1, a low dose of ANG II (175 ng.kg(-1).min(-1)) was infused into rats for 14 days. Plasma ANG II levels were not elevated after 14 days of infu sion. ANG II-infused rats did not gain weight over the 14-day protocol and exhibited a lower body weight than controls on day 8. Food intake was not altered, but water intake was increased in ANG II-infused rat s. Blood pressure gradually increased to significantly elevated levels by day 14. Thermal infrared imaging demonstrated an increase in abdom inal surface temperature. Measurement of organ mass demonstrated site- specific reductions in white adipose tissue mass after ANG II infusion . In stud 2, the dose-response relationship for ANC II infusion (200, 350, and 500 ng.kg(-1).min(-1)) was determined. Body weight (decrease) , blood pressure (increase), white adipose mass (decrease), plasma ANG II levels (increase), and plasma leptin levels (decrease) were altere d in a dose-related manner after ANG II infusion. In study 3, the effe ct of ANG II infusion (350 ng.kg(-1).min(-1)) was examined in rats tre ated with the vasodilator hydralazine. Hydralazine treatment normalize d blood pressure in ANG II-infused rats. The effect of ANG II to decre ase body weight was augmented in hydralazine-treated rats. These resul ts demonstrate that low levels of ANG II infusion regulate body weight through mechanisms related to increased peripheral metabolism and ind ependent of elevations in blood pressure.