Upregulation of vascular inducible nitric oxide synthase mediates the hypotensive effect of ethanol in conscious female rats
Upregulation of vascular inducible nitric oxide synthase mediates the hypotensive effect of ethanol in conscious female rats
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DOI：
10.1152/japplphysiol.01058.2005
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发表时间：
2006-03-01
影响因子：
3.3
通讯作者：
Abdel-Rahman, AA
中科院分区：
文献类型：
--
作者：
El-Mas, MM;Zhang, J;Abdel-Rahman, AA
在本研究中，我们验证了乙醇通过上调血管组织中的诱导型一氧化氮合酶（iNOS）来降低雌性大鼠血压的假设。研究了n - g -硝基-(L)-精氨酸（NOARG；非选择性一氧化氮合酶抑制剂）或氨基胍（选择性一氧化氮合酶抑制剂）预处理对清醒雌性大鼠灌胃乙醇引起的血流动力学反应的影响。用免疫组织化学方法检测在氨基胍存在和不存在的情况下，乙醇引起的血管（主动脉）iNOS蛋白表达的变化。与对照组（水处理）雌性大鼠相比，乙醇（1 g/kg ig）引起低血压，并显著增加主动脉iNOS活性。在注入一氧化氮合酶抑制剂NOARG的大鼠中，乙醇的降压作用几乎被消除，提示一氧化氮在乙醇降压中起作用。乙醇不能降低noarg治疗大鼠的血压，不能归因于这些大鼠血压升高，因为当血压升高到与苯肾上腺素输注相当的水平时，乙醇会产生低血压。氨基胍选择性抑制iNOS （45 mg/kg / ip）对基线血压没有影响，但同时消除了随后给药乙醇的降压作用和相关的主动脉iNOS含量增加。这些发现表明，至少在一定程度上，乙醇对雌性大鼠的急性降压作用与血管iNOS有关。
In the present study, we tested the hypothesis that ethanol lowers blood pressure in female rats via upregulation of the inducible nitric oxide synthase (iNOS) in vascular tissues. The effects of pretreatment with N-G-nitro-(L)-arginine (NOARG; nonselective nitric oxide synthase inhibitor) or aminoguanidine (selective iNOS inhibitor) on hemodynamic responses elicited by intragastric (ig) ethanol were determined in conscious female rats. Changes in vascular (aortic) iNOS protein expression evoked by ethanol in the presence and absence of aminoguanidine were also measured by immunohistochemistry. Compared with control ( water treated) female rats, ethanol (1 g/kg ig) elicited hypotension that was associated with a significant increase in the aortic iNOS activity. The hypotensive effect of ethanol was virtually abolished in rats infused with the nitric oxide synthase inhibitor NOARG, suggesting a role for nitric oxide in ethanol hypotension. The inability of ethanol to lower blood pressure in NOARG-treated rats cannot be attributed to the presence of elevated blood pressure in these rats because ethanol produced hypotension when blood pressure was raised to comparable levels with phenylephrine infusion. Selective inhibition of iNOS by aminoguanidine (45 mg/kg ip), which had no effect on baseline blood pressure, abolished both the hypotensive action of subsequently administered ethanol and the associated increases in aortic iNOS content. These findings implicate vascular iNOS, at least partly, in the acute hypotensive action of ethanol in female rats.