Figure 2. Endothelial cell-restricted ET-1 overexpression did not increase blood pressure, impair EDR, or reduce eNOS activity.

A) Representative image of PCR genotyping gel of wild-type (wt) and endothelin-1 (ET-1) overexpressing transgenic (tg) mice. Aortic (e.g., vascular) and plasma endothelin-1 (ET-1) concentrations as determined by ELISA; n=18–21/group. B) Visualization of aortic ET-1 content via immunofluorescent confocal microscopy in wt and tg mice. L denotes lumen; (−) denotes negative control. C) Mean arterial blood pressure (MAP) as determined by tail-cuff blood pressure monitoring; n=18–21/group. D) Aortic vasoconstriction responses to phenylephrine (PE; n=16–19/group) and ET-1 (n=5–11/group). Aortic rings were pre-treated with L-NAME (300μM for 30 min) to limit confounding effects of nitric oxide production on vascular tone and isolate the effects of ET-1 on vasoconstriction. E) Endothelium-dependent (ACh, ACH/SNP) and –independent (SNP) vasomotor function responses in the aorta, femoral artery, and coronary artery in wt and tg mice; n=12–19/genotype/artery. Vasomotor function responses were determined via wire myography (aorta and coronary artery) or pressure myography (femoral artery). F) Western blot determination of aortic eNOS activation (p-eNOS Ser1177/total eNOS) and endothelin receptor A (ET_A) and receptor B (ET_B) in aortic homogenates from wt and tg mice. Representative Western blot images are depicted. Proteins of interest were normalized to the housekeeping protein, vinculin; n=18–19/group. All data are expressed as means ± SEM. *p<0.05 vs wt. AUC, area under the curve.