Passaglia Patrícia, Ceron Carla S, Mecawi André S, Antunes-Rodrigues José, Coelho Eduardo B, Tirapelli Carlos R
Programa de pós-graduação em Toxicologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil; Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil.
Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil.
Vascul Pharmacol. 2015 Nov;74:49-59. doi: 10.1016/j.vph.2015.04.002. Epub 2015 Apr 11.
We hypothesized that chronic ethanol intake enhances vascular oxidative stress and induces hypertension through renin-angiotensin system (RAS) activation.
Male Wistar rats were treated with ethanol (20% v/v). The increase in blood pressure induced by ethanol was prevented by losartan (10mg/kg/day; p.o. gavage), a selective AT1 receptor antagonist. Chronic ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels and serum aldosterone levels. No differences on plasma osmolality and sodium or potassium levels were detected after treatment with ethanol. Ethanol consumption did not alter ACE activity, as well as the levels of ANG I and ANG II in the rat aorta or mesenteric arterial bed (MAB). Ethanol induced systemic and vascular oxidative stress (aorta and MAB) and these effects were prevented by losartan. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was prevented by losartan. Ethanol intake did not alter protein expression of ACE, AT1 or AT2 receptors in both aorta and MAB. Aortas from ethanol-treated rats displayed decreased ERK1/2 phosphorylation and increased protein expression of SAPK/JNK. These responses were prevented by losartan. MAB from ethanol-treated rats displayed reduced phosphorylation of p38MAPK and ERK1/2 and losartan did not prevent these responses.
Our study provides novel evidence that chronic ethanol intake increases blood pressure, induces vascular oxidative stress and decreases nitric oxide (NO) bioavailability through AT1-dependent mechanisms.
我们假设长期摄入乙醇会增强血管氧化应激，并通过肾素 - 血管紧张素系统（RAS）激活诱发高血压。
用乙醇（20% v/v）处理雄性Wistar大鼠。氯沙坦（10mg/kg/天；口服灌胃），一种选择性AT1受体拮抗剂，可预防乙醇诱导的血压升高。长期摄入乙醇会增加血浆肾素活性（PRA）、血管紧张素转换酶（ACE）活性、血浆血管紧张素I（ANG I）和血管紧张素II（ANG II）水平以及血清醛固酮水平。用乙醇处理后，未检测到血浆渗透压、钠或钾水平的差异。乙醇摄入并未改变大鼠主动脉或肠系膜动脉床（MAB）中的ACE活性以及ANG I和ANG II水平。乙醇诱导全身和血管氧化应激（主动脉和MAB），而氯沙坦可预防这些作用。氯沙坦可预防乙醇诱导的血浆和血管中硝酸盐/亚硝酸盐（NOx）水平降低。乙醇摄入并未改变主动脉和MAB中ACE、AT1或AT2受体的蛋白表达。乙醇处理大鼠的主动脉显示ERK1/2磷酸化降低，而SAPK/JNK蛋白表达增加。这些反应可被氯沙坦预防。乙醇处理大鼠的MAB显示p38MAPK和ERK1/2磷酸化降低，氯沙坦不能预防这些反应。
我们的研究提供了新的证据，即长期摄入乙醇会通过AT1依赖机制升高血压、诱导血管氧化应激并降低一氧化氮（NO）生物利用度。
