Abstract 159: Role of Melanocortin 3/4 Receptor (MC3/4R) in a Model of Postmenopausal Hypertension.
The mechanisms responsible for hypertension in postmenopausal women have not been completely elucidated. We have shown previously that MAP in old female SHR is mediated in part by sympathetic activation. In male SHR leptin causes sympathetic activation via the melanocortin 3 / 4 receptor (MC3/4R) activation, and MC3/4R blockade reduces their blood pressure. The hypothesis of the present study was that MC3/4R also contributes to hypertension in old female SHR. Female SHR (aged 18 mos, n=6) received MC3/4 receptor antagonist SHU-9119 (1 nmol/h via minipump) or saline vehicle (n=5 controls). After two weeks recovery, MAP and heart rate (HR) were measured for 5 days during baseline period, and then rats received SHU 9119 or saline icv, and MAP and HR were recorded for 7 days. MC3/4R antagonism produced an increase in food intake (17.1±2 gr, n=5, vs 26.6±1 gr, n=6, p<0.001) and body weight (217±11 gr,n=5 vs 256±6 gr, n=6; p<0.001), compared to saline controls. However, MC3/4R antagonism had no effect on MAP (baseline period: 174±10 mmHg ,n=4 vs 181±5 mmHg, n=6; p:NS; treatment period, 175±13 mmHg, n=4 vs 172±10 mmHg, n=6; p:NS) or HR (Baseline period: 344±4 bpm, n=4 vs 357±12 bpm, n=6; Treatment period, V-R:345±9 bpm, n=4 vs 332±9 bpm, n=6; p:NS). These results show that MC3/4R plays no role in sympathetic activation and regulation of BP in old female SHR. These data suggest that aging women may need different antihypertensive medications than do men. Supported by NIH HL69192, HL55901; HL66072.
- © 2012 by American Heart Association, Inc.