Abstract 079: G Protein-Coupled Estrogen Receptor Deletion Exacerbates Pulse Pressure in Female but not Male Hypertensive Mice
The protective cardiovascular effects of estrogen are mediated by both the classic steroid receptors (ERα/β) and the novel G protein-coupled estrogen receptor (GPER). Our previous work demonstrates a role for GPER in the beneficial effects of estrogen on blood pressure, vascular tone, end organ damage, and aortic remodeling in hypertensive females, due to both direct vasodilatory effects and local regulation of the renin-angiotensin system. Therefore, we hypothesized that genetic deletion of GPER in female mice exacerbates Ang II-induced hypertension and associated tissue damage. Male (M) and female (F) wt and GPER ko mice were implanted with radiotelemetry probes at 11-13 weeks of age to measure baseline blood pressure before infusing Ang II (700 ng/kg/min) for two weeks. MAP (in mmHg) was similar at baseline (F-wt: 108 ± 2, n=4, F-ko: 105 ± 2, n=3, M-wt: 106 ± 4, n=3, and M-ko: 105 ± 0.5, n=3; P = 0.62), and after Ang II (F-wt: 136 ± 11, F-ko: 131 ± 3, M-wt: 148 ± 7, M-ko: 135 ± 5; P=0.51). Pulse pressure was significantly higher in response to Ang II in both sexes (*P<0.0001), and GPER deletion exacerbated this increase in females (30 ± 1 vs 43 ± 4 mmHg, *P<0.05) but not males (37 ± 3 vs. 39 ± 4, P=0.61). Further evaluation of the circadian pattern revealed that pulse pressure was particularly higher in F-ko during the day (28 ± 1 vs. 40 ± 4 mmHg, *P<0.05). Moreover, F-ko mesenteric arteries exhibited enhanced contractility to both receptor-dependent (PGF2α, *P<0.05) and receptor-independent (KCl, *P<0.05) stimulation. Our findings indicate that in females with intact ERα/β signaling, GPER deletion does not alter the initial pressor response to Ang II but exacerbates pulse pressure and resistance artery contractility during hypertension. Pulse pressure is an indirect measure of arterial stiffness and an independent risk factor for adverse cardiovascular events. While pulse pressure increases with aging in both sexes, this increase is markedly exacerbated in women. Our results indicate that loss of endogenous GPER activation due to low circulating estrogen may underlie increased pulse pressure in aging postmenopausal women.
Author Disclosures: S.H. Lindsey: None. E.H. Trimmer: None. M.A. Zimmerman: None.
- © 2015 by American Heart Association, Inc.