Noll Laboratory, Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania.
Department of Kinesiology, University of Texas Arlington, Arlington, Texas.
Am J Physiol Heart Circ Physiol. 2020 Sep 1;319(3):H539-H546. doi: 10.1152/ajpheart.00179.2020. Epub 2020 Jul 31.
In 2017, the American Heart Association (AHA) and American College of Cardiology (ACC) redefined stage 1 hypertension to systolic blood pressure (BP) 130-139 mmHg or diastolic BP 80-89 mmHg; however, the degree to which microvascular endothelial dysfunction is evident in adults with stage 1 hypertension remains equivocal. We tested the hypotheses that cutaneous microvascular endothelial dysfunction would be present in adults with stage 1 hypertension (HTN1) compared with normotensive adults (NTN; BP <120/<80 mmHg) but would be less severe compared with adults with stage 2 hypertension (HTN2; systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) and that this graded impairment would be mediated by reductions in nitric oxide (NO)-dependent dilation. This retrospective analysis included 20 NTN (5 men; 45-64 yr; BP 94-114/60-70 mmHg), 22 HTN1 (11 men; 40-74 yr; BP 110-134/70-88 mmHg), and 44 HTN2 (27 men; 40-74 yr; BP 128-180/80-110 mmHg). BP and nocturnal dipping status were also assessed using 24-h ambulatory BP monitoring. Red cell flux (laser Doppler flowmetry) was measured during intradermal microdialysis perfusion of acetylcholine (ACh; 10 to 10M) alone and concurrently with the nonspecific nitric oxide (NO) synthase inhibitor -nitro-l-arginine methyl ester (l-NAME; 15 mM). ACh-induced dilation was impaired in HTN2 ( < 0.01), but not in HTN1 ( = 0.85), compared with NTN. Furthermore, reductions in NO-dependent dilation were evident in HTN2 ( < 0.01) but not in HTN1 ( = 0.76). Regardless of BP, endothelium-dependent dilation was impaired in nondippers (nighttime drop in systolic BP <10%) compared with dippers (nighttime drop in systolic BP ≥10%, < 0.05). In conclusion, functional impairments in NO-mediated endothelium-dependent dilation were not evident in HTN1. However, regardless of BP classification, the lack of a nocturnal dip in BP was associated with blunted endothelium-dependent dilation. This is the first study to pharmacologically assess the mechanistic regulation of endothelial function in adults with hypertension, classified according to the 2017 clinical guidelines set for by the American Heart Association (AHA) and American College of Cardiology (ACC). Compared with that in normotensive adults, nitric oxide-mediated endothelium-dependent dilation is impaired in adults with stage 2, but not stage 1, hypertension. Adults lacking a nighttime dip in blood pressure demonstrated reductions in endothelium-dependent dilation.
2017 年,美国心脏协会(AHA)和美国心脏病学会(ACC)重新定义了 1 期高血压,收缩压(BP)为 130-139mmHg 或舒张压(BP)为 80-89mmHg;然而,1 期高血压患者微血管内皮功能障碍的程度仍存在争议。我们检验了以下假设:与正常血压成年人(NTN;BP<120/<80mmHg)相比,1 期高血压(HTN1)成年人存在皮肤微血管内皮功能障碍,但与 2 期高血压(HTN2;收缩压≥140mmHg 或舒张压≥90mmHg)成年人相比,这种功能障碍的严重程度较轻,这种分级损伤是由一氧化氮(NO)依赖性扩张减少介导的。这项回顾性分析纳入了 20 名 NTN(5 名男性;45-64 岁;BP94-114/60-70mmHg)、22 名 HTN1(11 名男性;40-74 岁;BP110-134/70-88mmHg)和 44 名 HTN2(27 名男性;40-74 岁;BP128-180/80-110mmHg)。使用 24 小时动态血压监测评估血压和夜间血压下降状态。在皮肤内微透析灌注乙酰胆碱(ACh;10 至 10M)的同时,通过激光多普勒血流仪测量红细胞通量,同时使用非特异性一氧化氮(NO)合酶抑制剂硝基-L-精氨酸甲酯(L-NAME;15mM)。与 NTN 相比,HTN2(<0.01)而不是 HTN1(=0.85)中 ACh 诱导的扩张受损。此外,HTN2(<0.01)中可见依赖于 NO 的扩张减少,但 HTN1(=0.76)中未见。无论血压如何,夜间血压下降<10%的非夜间血压下降者(夜间收缩压下降)与夜间血压下降≥10%的夜间血压下降者(<0.05)相比,内皮依赖性扩张受损。总之,HTN1 中未发现 NO 介导的内皮依赖性扩张功能障碍。然而,无论血压分类如何,夜间血压无下降与内皮依赖性扩张受损有关。这是第一项根据美国心脏协会(AHA)和美国心脏病学会(ACC)制定的 2017 年临床指南,对高血压成年人中内皮功能的机械调节进行药理学评估的研究。与正常血压成年人相比,2 期高血压患者中,而不是 1 期高血压患者中,一氧化氮介导的内皮依赖性扩张受损。夜间血压无下降的成年人表现出内皮依赖性扩张减少。