Acute ethanol intake induces mitogen-activated protein kinase activation, platelet-derived growth factor receptor phosphorylation, and oxidative stress in resistance arteries
Acute ethanol intake induces mitogen-activated protein kinase activation, platelet-derived growth factor receptor phosphorylation, and oxidative stress in resistance arteries
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DOI：
10.1007/s13105-014-0331-6
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发表时间：
2014-06-01
影响因子：
3.4
通讯作者：
Tirapelli, Carlos R.
中科院分区：
文献类型：
--
作者：
Gonzaga, Natalia A.;Callera, Glaucia E.;Tirapelli, Carlos R.
在本研究中，我们研究了 I 型血管紧张素 (AT(1)) 受体在阻力动脉中急性乙醇摄入诱导的活性氧 (ROS) 生成和丝裂原激活蛋白激酶 (MAPK) 激活中的作用。我们还评估了乙醇对血小板源性生长因子受体 (PDGF-R) 磷酸化的影响以及该受体对乙醇产生 ROS 的作用。在 30 分钟内对雄性 Wistar 大鼠评估乙醇（1 g/kg；口服灌胃）的影响。急性乙醇摄入不会改变大鼠肠系膜动脉床 (MAB) 中的血管紧张素 I 或血管紧张素 II 水平。乙醇诱导血管氧化应激，并且这种反应不能被选择性 AT1 受体拮抗剂氯沙坦（10 mg/kg；口服灌胃）阻止。来自乙醇处理的大鼠的 MAB 显示 SAPK/JNK 和 PDGF-R 磷酸化增加，而氯沙坦无法阻止这种反应。蛋白激酶 B (Akt) 和 eNOS 的磷酸化水平不受急性乙醇摄入的影响。 MAB 硝酸盐水平以及该组织对乙酰胆碱、去氧肾上腺素和硝普钠的反应性不受乙醇摄入的影响。乙醇不会改变大鼠 MAB 中的血浆抗氧化能力、还原型谷胱甘肽水平或超氧化物歧化酶和过氧化氢酶的活性。在从大鼠 MAB 中分离的血管平滑肌细胞 (VSMC) 中评估乙醇 (50 mmol/l) 的短期影响。乙醇增加了 ROS 的产生，并且这种反应不受 PDGF-R 抑制剂 AG1296 或氯沙坦的影响。最后，乙醇不会改变培养的 VSMC 中的 MAPK 或 PDGF-R 磷酸化。我们的研究提供了新的证据，证明急性乙醇摄入可通过体内阻力动脉中的 AT(1) 独立机制诱导 ROS 生成、PDGF-R 磷酸化和 MAPK 激活。 MAPK 和 PDGF-R 在血管信号传导和心血管疾病中发挥作用，并可能有助于乙醇的血管病理学。
In the present study, we investigated the role of angiotensin type I (AT(1)) receptor in reactive oxygen species (ROS) generation and mitogen-activated protein kinases (MAPK) activation induced by acute ethanol intake in resistance arteries. We also evaluated the effect of ethanol on platelet-derived growth factor receptors (PDGF-R) phosphorylation and the role of this receptor on ROS generation by ethanol. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. Acute ethanol intake did not alter angiotensin I or angiotensin II levels in the rat mesenteric arterial bed (MAB). Ethanol induced vascular oxidative stress, and this response was not prevented by losartan (10 mg/kg; p.o. gavage), a selective AT1 receptor antagonist. MAB from ethanol-treated rats displayed increased SAPK/JNK and PDGF-R phosphorylation, responses that were not prevented by losartan. The phosphorylation levels of protein kinase B (Akt) and eNOS were not affected by acute ethanol intake. MAB nitrate levels and the reactivity of this tissue to acetylcholine, phenylephrine, and sodium nitroprusside were not affected by ethanol intake. Ethanol did not alter plasma antioxidant capacity, the levels of reduced glutathione, or the activities of superoxide dismutase and catalase in the rat MAB. Short-term effects of ethanol (50 mmol/l) were evaluated in vascular smooth muscle cells (VSMC) isolated from rat MAB. Ethanol increased ROS generation, and this response was not affected by AG1296, a PDGF-R inhibitor, or losartan. Finally, ethanol did not alter MAPK or PDGF-R phosphorylation in cultured VSMC. Our study provides novel evidence that acute ethanol intake induces ROS generation, PDGF-R phosphorylation, and MAPK activation through AT(1)-independent mechanisms in resistance arteries in vivo. MAPK and PDGF-R play a role in vascular signaling and cardiovascular diseases and may contribute to the vascular pathobiology of ethanol.