Impaired Hydrogen Sulfide-Mediated Vasodilation Contributes to Microvascular Endothelial Dysfunction in Hypertensive Adults.
Impaired Hydrogen Sulfide-Mediated Vasodilation Contributes to Microvascular Endothelial Dysfunction in Hypertensive Adults.
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DOI：
10.1161/hypertensionaha.116.08964
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发表时间：
2017-05
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影响因子：
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通讯作者：
Alexander LM
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作者：
Greaney JL;Kutz JL;Shank SW;Jandu S;Santhanam L;Alexander LM
在高血压动物模型中，硫化氢（H2S）产生的减少与血管功能障碍的发病机制有关；然而，没有研究证实H2S在高血压（HTN）成人微血管功能障碍中的功能作用。我们假设内源性H2S的产生会减少，内皮依赖性血管舒张的受损将通过H2S依赖性血管舒张的减少来介导，并且与正常血压（NTN）的成年人相比，HTN的血管对外源性H2S （Na2S）的反应性会减弱。15个NTN[51±2年；血压（血压）116±3/76±3mmhg]和14名HTN成人（57±2岁；血压140±3/89±2mmhg）参与。在皮肤组织匀浆中测量H2S生物合成酶表达（Western blot）和底物依赖性H2S产生（安培探针）。采用皮内微透析法测量乙酰胆碱（ACh; 10−6 -10−1 mol∙L−1）和Na2S（10−5-101 mol∙L−1）分级灌注时红细胞通量（激光多普勒血流法）；采用氨基乙酸（AOAA; 0.5 mmol∙L−1）抑制H2S的功能作用。H2S生物合成酶表达和底物依赖性H2S生成在HTN成虫中降低（均p<0.05）。与NTN成人相比，HTN患者乙酰胆碱诱导的内皮依赖性血管舒张功能减弱（p=0.012）。AOAA减弱了NTN成人ACh诱导的血管舒张（ACh: 1.31±0.13 vs ACh+AOAA: 1.07±0.09 flux∙mmHg−1，P=0.025），但对HTN成人血管舒张无影响（ACh: 1.16±0.10 vs ACh+AOAA: 1.37±0.11 flux∙mmHg−1，P= 0.47）。na2s诱导的血管舒张在两组间无明显差异。总的来说，这些发现表明，虽然微血管在外源性H2S的作用下维持血管舒张能力，但内源性合成和H2S依赖性血管舒张的减少有助于高血压患者的内皮功能障碍。
Reductions in hydrogen sulfide (H2S) production have been implicated in the pathogenesis of vascular dysfunction in animal models of hypertension; however, no studies have examined a functional role for H2S contributing to microvascular dysfunction in hypertensive (HTN) adults. We hypothesized that endogenous production of H2S would be reduced, impaired endothelium-dependent vasodilation would be mediated by reductions in H2S-dependent vasodilation, and vascular responsiveness to exogenous H2S (Na2S) would be attenuated in HTN compared to normotensive (NTN) adults. Fifteen NTN [51±2 yrs; blood pressure (BP) 116±3/76±3 mmHg] and 14 HTN adults (57±2 yrs; BP 140±3/89±2 mmHg) participated. H2S biosynthetic enzyme expression (Western blot) and substrate-dependent H2S 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−1) and Na2S (10−5–101 mol∙L−1) using intradermal microdialysis; the functional role of H2S was determined using pharmacological inhibition with aminooxyacetic acid (AOAA; 0.5 mmol∙L−1). H2S biosynthetic enzyme expression and substrate-dependent H2S production were reduced in HTN adults (all p<0.05). ACh-induced endothelium-dependent vasodilation was blunted in HTN compared to NTN adults (p=0.012). AOAA attenuated ACh-induced vasodilation in NTN adults (ACh: 1.31±0.13 vs. ACh+AOAA: 1.07±0.09 flux∙mmHg−1; P=0.025) but had no effect on vasodilation in HTN adults (ACh: 1.16±0.10 v. ACh+AOAA: 1.37±0.11 flux∙mmHg−1; p=0.47). Na2S-induced vasodilation was not different between groups. Collectively, these findings indicate that while the microvasculature maintains the ability to vasodilate in response to exogenous H2S, reductions in endogenous synthesis and H2S-dependent vasodilation contribute to endothelial dysfunction in human hypertension.