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

<p>Reductions in hydrogen sulfide (HS) production have been implicated in the pathogenesis of vascular dysfunction in animal models of hypertension; however, no studies have examined a functional role for HS in contributing to microvascular dysfunction in hypertensive (HTN) adults. We hypothesized that endogenous production of HS would be reduced, impaired endothelium-dependent vasodilation would be mediated by reductions in HS-dependent vasodilation, and vascular responsiveness to exogenous HS (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. HS biosynthetic enzyme expression (Western blot) and substrate-dependent HS production (amperometric probe) were measured in cutaneous tissue homogenates. Red cell flux (laser Doppler flowmetry) was measured during graded perfusions of acetylcholine (ACh; 10-10 mol/L) and sodium sulfide (10-10 mol/L) using intradermal microdialysis; the functional role of HS was determined using pharmacological inhibition with aminooxyacetic acid (0.5 mmol/L). HS biosynthetic enzyme expression and substrate-dependent HS production were reduced in HTN adults (all <0.05). ACh-induced endothelium-dependent vasodilation was blunted in HTN adults (=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; =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; =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 HS, reductions in endogenous synthesis and HS-dependent vasodilation contribute to endothelial dysfunction in human hypertension.</p>