Abstract 113: Female Protection From Arterial Stiffness Diminishes With G Protein-Coupled Estrogen Receptor Deletion or Angiotensin II Hypertension

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Arterial stiffness independently predicts cardiovascular mortality, coronary events, and stroke in hypertensive subjects and is exacerbated in women following menopause. Previously, our laboratory indicated that G protein-coupled estrogen receptor (GPER) plays a protective role in the vasculature. Therefore, the current study assessed the impact of sex and GPER on arterial stiffening in control and hypertensive conditions. We hypothesized that genetic deletion of GPER attenuates sex differences in arterial stiffness. Male and female wildtype (wt) and global GPER knockout (ko) mice (n=46) were used between 16-21 weeks of age. Angiotensin II (Ang II) infusion (700 ng/kg/day for two weeks) was used to induce hypertension, and systolic blood pressure (SBP) was measured using tail cuff plethysmography. Local pulse wave velocity (PWV) within the carotid artery was obtained via high frequency ultrasound in both color Doppler and M-mode. Statistical analysis was performed using two-way ANOVA with Sidak’s multiple comparisons test. Baseline SBP was significantly lower in females (P=0.035) but was not impacted by genotype (P=0.78). Baseline PWV was significantly higher in male versus female wt mice (1.29 vs. 0.804 m/s, P=0.003) but was not different in ko mice (1.25 vs. 1.04 m/s, P=0.22). Ang II infusion significantly increased SBP (P<0.001) and PWV (P<0.001) in all groups, removing any impact of sex or genotype. In addition, significant correlations were found between Doppler and M-mode methods for obtaining carotid PWV (r=0.67, P<0.001) and between PWV and ex vivo carotid wall thickness (r=0.70, P=0.004). In contrast, SBP did not correlate with PWV (P=0.77) or carotid wall thickness (P=0.68). In conclusion, we found that GPER deletion did not impact blood pressure either in normotensive or hypertensive conditions. While arteries from female wt mice were less stiff at baseline, genetic deletion of GPER or Ang II infusion removed this protection independent of blood pressure. Moreover, we found that local carotid PWV provides information on vascular status that could not be obtained via blood pressure. This data indicates that GPER plays an important role in female vascular physiology that is absent in pathological conditions.