Abstract 18279: Roles of Aldosterone, Mineralocorticoid Inhibition and G6PD Activity in Microvascular Endothelial Dysfunction in African Americans with Hypertension
Systemic aldosterone levels are more strongly correlated with blood pressure in African Americans (AAs) than Caucasians, and aldosterone impairs vascular endothelial function in part by impairing G6PD activity in animal studies. The impact of physiological levels of aldosterone or acute mineralocorticoid blockade on microvascular endothelial function and G6PD activity in arterioles from AAs with and without hypertension (HTN) remains unclear.
37 AAs subjects (13 with HTN, 24 controls) underwent non-invasive studies of microvascular endothelial function using digital pulse arterial tonometry (DPAT). Systemic G6PD activity, renin, and aldosterone levels were measured. Subcutaneous gluteal arterioles were harvested from 15 of these subjects. Arteriolar endothelium-dependent vasodilation was testing using increasing doses of acetylcholine (Ach) and measured by videomicroscopy. Vessels were tested with or without 1 hour of pre-treatment with aldosterone (20 ng/dL) or spironolactone (10 μM). Arteriolar G6PD activity was also measured.
Vasodilation to Ach was decreased AAs with HTN compared to controls Arteriolar G6PD activity was significantly lower in arterioles for AAs with HTN (log transformed: 0.55±0.65 vs. 1.33±0.68 nmol NADPH/min/μg protein, P=0.02). Spironolactone reversed endothelial dysfunction in arterioles from AAs with HTN (P<0.001) with no impact on control vessels. Aldosterone impaired endothelial function (P=0.02, overall) in control arterioles. Smooth muscle reactivity to papaverine did not differ with any exposure. DPAT trended lower in AAs with hypertension (log transformed 0.47±0.38 vs. 0.68±0.32, P=0.10). No differences were seen between systemic aldosterone, renin, and G6PD activity. Systemic and arteriolar G6PD activity did not correlate.
Aldosterone impairs arteriolar endothelial function in normotensive AAs. G6PD activity is lower in arterioles from hypertensive AAs and acute mineralocorticoid inhibition reverses microvascular endothelial dysfunction. Systemic G6PD measurements do not reflect tissue level activity. Aldosterone’s impact on arteriolar endothelial function in AAs suggests its antagonism may have beneficial effects beyond blood pressure reduction.
Author Disclosures: T.M. Suboc: None. K. Dharmashankar: None. J. Wang: None. R. Ying: None. M.E. Widlansky: Research Grant; Significant; NIH, Doris Duke Foundation, Greater Milwaukee Wisconsin, Merck.
- © 2014 by American Heart Association, Inc.