Jasiczek Jakub, Trocha Małgorzata, Derkacz Arkadiusz, Szahidewicz-Krupska Ewa, Doroszko Adrian
Department of Cardiology, Provincial Specialized Hospital in Wroclaw, Kamienskiego 73a, 51-124 Wroclaw, Poland.
Department of Pharmacology, Faculty of Medicine, Wroclaw Medical University, Mikulicz-Radecki 2, 50-349 Wroclaw, Poland.
J Clin Med. 2021 Dec 13;10(24):5816. doi: 10.3390/jcm10245816.
The aim of the study was to evaluate the relationship between renin-angiotensin-aldosterone (RAA) system activity and reactivity, and the endothelial function profile in normotensive subjects (N), and in essential hypertensives (H), followed by analysis of the modulatory role of an angiotensin receptor blocker (ARB): valsartan, administered in the management of hypertension.
A total of 101 male subjects were enrolled to the study: 31H and 70N. The nitric-oxide (NO) bioavailability (l-Arginine, asymmetric dimethylarginine (ADMA)), symmetric dimethylarginine (SDMA), endothelial vasodilative function (flow mediated dilation (FMD)), oxidative-stress markers (malonyldialdehyde (MDA), thiol index (GSH/GSSG), nitrotyrozine (-Tyr)), and pro-inflammatory/angiogenic parameters (sICAM-1, sVCAM-1, PAI-1, sE-selectin, PAI-1, thromboxane -B2) were assessed at baseline, then after intravenous -l-arginine administration, which was repeated after the 4-day acetylsalicylic acid (ASA) administration (75 mg/24 h). In hypertensives, this whole protocol was repeated following 2 weeks of valsartan therapy.
No effect of valsartan and ASA on the flow-mediated vasodilation (FMD) and the NO bioavailability in hypertensives was observed. Administration of valsartan increased plasma renin activity (PRA), but without a decrease in the aldosterone levels. ASA treatment minimized the pre-existing differences between the groups, and increased the PRA in the N-subgroup with the highest ARR values. The blood concentrations of proinflammatory sICAM-1, sE-selectin, sVCAM-1, and PAI-1 were higher, whereas the anti-inflammatory 6-keto-PGF1 alpha level was lower in hypertensive subjects. The levels of angiogenic VEGF did not differ between groups.
Our study does not confirm the modulative effect of valsartan on endothelial function. Normotensive men showed an increase in FMD after l-arginine administration, possibly indicating baseline impairment of the NO synthesis.
本研究旨在评估肾素-血管紧张素-醛固酮（RAA）系统活性与反应性，以及血压正常受试者（N）和原发性高血压患者（H）的内皮功能概况，随后分析血管紧张素受体阻滞剂（ARB）缬沙坦在高血压治疗中的调节作用。
共有101名男性受试者参与本研究：31名H组受试者和70名N组受试者。在基线时评估一氧化氮（NO）生物利用度（L-精氨酸、不对称二甲基精氨酸（ADMA））、对称二甲基精氨酸（SDMA）、内皮舒张功能（血流介导的舒张（FMD））、氧化应激标志物（丙二醛（MDA）、硫醇指数（GSH/GSSG）、硝基酪氨酸（-Tyr））以及促炎/血管生成参数（可溶性细胞间黏附分子-1（sICAM-1）、可溶性血管细胞黏附分子-1（sVCAM-1）、纤溶酶原激活物抑制剂-1（PAI-1）、可溶性E-选择素、PAI-1、血栓素B2），然后在静脉注射L-精氨酸后再次评估，在给予4天乙酰水杨酸（ASA）（75mg/24h）后重复评估。在高血压患者中，在缬沙坦治疗2周后重复整个方案。
未观察到缬沙坦和ASA对高血压患者血流介导的血管舒张（FMD）和NO生物利用度有影响。给予缬沙坦可增加血浆肾素活性（PRA），但醛固酮水平未降低。ASA治疗使各组之间先前存在的差异最小化，并增加了ARR值最高的N亚组中的PRA。高血压患者促炎sICAM-1、sE-选择素、sVCAM-1和PAI-1的血药浓度较高，而抗炎6-酮-前列环素F1α水平较低。血管生成性血管内皮生长因子（VEGF）水平在各组之间无差异。
我们的研究未证实缬沙坦对内皮功能的调节作用。血压正常的男性在给予L-精氨酸后FMD增加，这可能表明NO合成存在基线损害。
