Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil; Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
Biochem Pharmacol. 2023 Nov;217:115840. doi: 10.1016/j.bcp.2023.115840. Epub 2023 Oct 1.
Ethanol consumption activates renin-angiotensin-aldosterone system (RAAS), which plays a major role in the pro-contractile and hypertensive effects linked to ethanol. We hypothesized that ethanol consumption induces loss of the anticontractile effect of perivascular adipose tissue (PVAT)through RAAS-mediated mechanisms. We examined the contribution of angiotensin II type 1 receptors (ATR) to ethanol-induced PVAT dysfunction. With this purpose, male Wistar Hannover rats were treated with ethanol 20 % (in volume ratio) and/or losartan (antagonist of ATR; 10 mg/kg/day, gavage) for 9 weeks. Losartan prevented the increase in blood pressure and the loss of the anticontractile effect of PVAT induced by ethanol consumption. PVAT dysfunction occurred after 3 and 9 weeks of treatment with ethanol in an endothelium-dependent manner. Blockade of ATR prevented ethanol-induced reduction of adiponectin levels in PVAT from ethanol-treated rats. Functional assays revealed that ethanol impaired the anticontractile effect of PVAT-derived angiotensin (1-7) and endothelial nitric oxide (NO). In conclusion, ATR are implicated in ethanol-induced loss of the anticontractile effect of PVAT. In PVAT, ATR activation decreases the production of adiponectin, a PVAT-derived factor that promotes vasorelaxation in an endothelium-dependent manner. In the endothelium, ATR favors the production of superoxide (O) leading to a reduction in NO bioavailability. These responses impair the vasodilator action induced by PVAT-derived angiotensin (1-7), which occurs via Mas receptors located in endothelial cells. Ethanol-induced PVAT dysfunction favors vascular hypercontractility, a response that could contribute to the hypertensive state associated with ethanol consumption.
乙醇摄入会激活肾素-血管紧张素-醛固酮系统（RAAS），该系统在与乙醇相关的促收缩和高血压效应中起着主要作用。我们假设，乙醇摄入通过 RAAS 介导的机制诱导血管周围脂肪组织（PVAT）的抗收缩作用丧失。我们研究了血管紧张素 II 型 1 受体（ATR）在乙醇诱导的 PVAT 功能障碍中的作用。为此，雄性 Wistar 汉诺威大鼠用乙醇 20%（按体积比）和/或氯沙坦（ATR 拮抗剂；10mg/kg/天，灌胃）处理 9 周。氯沙坦可预防乙醇摄入引起的血压升高和 PVAT 抗收缩作用丧失。乙醇处理 3 和 9 周后，PVAT 出现内皮依赖性功能障碍。ATR 阻断可预防乙醇诱导的乙醇处理大鼠 PVAT 中脂联素水平降低。功能测定表明，乙醇可损害 PVAT 衍生的血管紧张素（1-7）和内皮型一氧化氮（NO）的抗收缩作用。总之，ATR 参与了乙醇诱导的 PVAT 抗收缩作用丧失。在 PVAT 中，ATR 激活会降低脂联素的产生，脂联素是一种 PVAT 衍生的因子，可通过内皮依赖性方式促进血管舒张。在内皮细胞中，ATR 有利于超氧化物（O）的产生，从而导致 NO 生物利用度降低。这些反应损害了由 PVAT 衍生的血管紧张素（1-7）诱导的血管舒张作用，该作用通过位于内皮细胞中的 Mas 受体发生。乙醇诱导的 PVAT 功能障碍有利于血管过度收缩，这种反应可能有助于与乙醇摄入相关的高血压状态。
