Hypertension is characterized by systemic microvascular endothelial dysfunction, in part due to a functional absence of hydrogen sulfide (H₂S)-mediated endothelium-dependent dilation. Treatment with a sulfhydryl-donating ACE-inhibitor (SH-ACE-inhibitor) improves endothelial function in pre-clinical models of hypertension. To date, no studies have directly assessed the effects of SH-ACE-inhibitor treatment on H₂S-dependent vasodilation in hypertensive humans. We hypothesized that SH-ACE-inhibitor treatment would improve H₂S-mediated endothelium-dependent vasodilation. Ten hypertensive adults (1W; 56±9yrs, Systolic BP: 141±8.5 mmHg; Diastolic BP: 90.3±6 mmHg) were treated (16 weeks) with the SH-ACE-inhibitor captopril. Red blood cell flux (laser Doppler flowmetry) was measured continuously during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine (ACh; 10^-10-10^-1 M) alone (control) and in combination with an inhibitor of enzymatic H₂S production (10^-3 M aminooxyacetate; AOAA) pre- and post-intervention. Cutaneous vascular conductance (CVC; flux/mmHg) was calculated and normalized to the site-specific maximal CVC (0.028M sodium nitroprusside and local heat to 43°C). Area-under-the-curve was calculated using the trapezoid method. The 16-week SH-ACE-inhibitor treatment resulted in a reduction of blood pressure (Systolic BP: 129±10 mmHg; Diastolic BP: 81 ±9 mmHg, both p<0.05). Pre-intervention, inhibition of H₂S production had no effect on ACh-induced vasodilation (316±40 control vs 322±35 AU AOAA; p=0.82). Captopril treatment improved ACh-induced vasodilation (316±40 pre vs 399±55 AU post; p=0.04) and increased the H₂S-dependent component of ACh-induced vasodilation (pre: -6.6 ± 65.1 vs post: 90.2 ± 148.3 AU, p=0.04). These data suggest that SH-ACE-inhibitor antihypertensive treatment improves cutaneous microvascular endothelium-dependent vasodilation in hypertensive adults, in part via H₂S-dependent mechanisms.

中文翻译：

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在高血压成人中接受慢性巯基供体抗高血压药物治疗后，硫化氢依赖性微血管舒张得到改善。

高血压的特征在于全身微血管内皮功能障碍，部分原因是硫化氢 (H ₂ S) 介导的内皮依赖性扩张功能缺失。使用巯基供体 ACE 抑制剂（SH-ACE 抑制剂）治疗可改善高血压临床前模型中的内皮功能。迄今为止，尚无研究直接评估了 SH-ACE 抑制剂治疗对高血压人群中H ₂ S 依赖性血管舒张的影响。我们假设 SH-ACE 抑制剂治疗会改善 H ₂S 介导的内皮依赖性血管舒张。10 名高血压成人（1W；56±9 岁，收缩压：141±8.5 mmHg；舒张压：90.3±6 mmHg）接受了 SH-ACE 抑制剂卡托普利治疗（16 周）。在内皮依赖性激动剂乙酰胆碱（ACh；10 ^-10 -10 ^-1 M）单独（对照）和与酶促 H ₂抑制剂组合的分级皮内微透析灌注期间连续测量红细胞流量（激光多普勒血流仪）S产量（10 ^-3M氨基氧乙酸盐；AOAA) 干预前和干预后。计算皮肤血管电导（CVC；通量/mmHg）并将其标准化为特定部位的最大 CVC（0.028M 硝普钠和局部加热至 43°C）。曲线下面积使用梯形法计算。16 周 SH-ACE 抑制剂治疗导致血压降低（收缩压：129±10 mmHg；舒张压：81±9 mmHg，两者 p<0.05）。干预前，H ₂ S 产生的抑制对乙酰胆碱诱导的血管舒张没有影响（316±40 对照对 322±35 AU AOAA；p=0.82）。卡托普利治疗改善了 ACh 诱导的血管舒张（316±40 前 vs 399±55 AU 后；p=0.04）并增加了 H ₂ACh 诱导的血管舒张的 S 依赖性成分（前：-6.6 ± 65.1 与后：90.2 ± 148.3 AU，p=0.04）。这些数据表明，SH-ACE 抑制剂抗高血压治疗改善了高血压成人的皮肤微血管内皮依赖性血管舒张，部分通过 H ₂ S 依赖性机制。