Impaired Hydrogen Sulfide–Mediated Vasodilation Contributes to Microvascular Endothelial Dysfunction in Hypertensive Adults

Abstract

Reductions in hydrogen sulfide (H 2 S) production have been implicated in the pathogenesis of vascular dysfunction in animal models of hypertension; however, no studies have examined a functional role for H 2 S in contributing to microvascular dysfunction in hypertensive (HTN) adults. We hypothesized that endogenous production of H 2 S would be reduced, impaired endothelium-dependent vasodilation would be mediated by reductions in H 2 S-dependent vasodilation, and vascular responsiveness to exogenous H 2 S (sodium sulfide) would be attenuated in HTN compared to normotensive adults. Fifteen normotensive (51±2 years; blood pressure, 116±3/76±3 mm Hg) and 14 HTN adults (57±2 years; blood pressure 140±3/89±2 mm Hg) participated. H 2 S biosynthetic enzyme expression (Western blot) and substrate-dependent H 2 S production (amperometric probe) were measured in cutaneous tissue homogenates. Red cell flux (laser Doppler flowmetry) was measured during graded perfusions of acetylcholine (ACh; 10 –6 –10 –1 mol/L) and sodium sulfide (10 –5 –10 1 mol/L) using intradermal microdialysis; the functional role of H 2 S was determined using pharmacological inhibition with aminooxyacetic acid (0.5 mmol/L). H 2 S biosynthetic enzyme expression and substrate-dependent H 2 S production were reduced in HTN adults (all P <0.05). ACh-induced endothelium-dependent vasodilation was blunted in HTN adults ( P =0.012). Aminooxyacetic acid attenuated ACh-induced vasodilation in normotensive adults (ACh, 1.31±0.13 versus ACh+aminooxyacetic acid, 1.07±0.09 flux/mm Hg; P =0.025) but had no effect on vasodilation in HTN adults (ACh, 1.16±0.10 versus ACh+aminooxyacetic acid, 1.37±0.11 flux/mm Hg; P =0.47). Sodium sulfide–induced vasodilation was not different between groups. Collectively, these findings indicate that while the microvasculature maintains the ability to vasodilate in response to exogenous H 2 S, reductions in endogenous synthesis and H 2 S-dependent vasodilation contribute to endothelial dysfunction in human hypertension.