Facilitation of myocardial PI3K/Akt/nNOS signaling contributes to ethanol-evoked hypotension in female rats.
Facilitation of myocardial PI3K/Akt/nNOS signaling contributes to ethanol-evoked hypotension in female rats.
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DOI：
10.1111/j.1530-0277.2009.00939.x
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Abdel-Rahman AA
中科院分区：
文献类型：
--
作者：
El-Mas MM;Fan M;Abdel-Rahman AA
乙醇降低雌性大鼠心输出量（CO）和血压（BP）的机制尚不清楚。我们检验了以下假设：心肌磷脂酰肌醇3-激酶（PI 3 K）/Akt信号传导和相关nNOS和/或eNOS活性的增强构成了乙醇血流动力学效应的细胞机制。方法：采用免疫组织化学方法检测大鼠心肌组织中磷酸化eNOS（p-eNOS）和p-nNOS的水平。沿着给药的雌性大鼠的血液动力学反应（BP、CO、每搏输出量、SV、总外周阻力、TPR）和心肌硝酸盐/亚硝酸盐水平（NOx）。此外，我们研究了用Nω-丙基-L-精氨酸选择性药理学抑制nNOS或用N5-（1-亚氨基乙基）-L-鸟氨酸选择性药理学抑制eNOS对乙醇的细胞、血液动力学和生化效应的影响。研究了Wortmannin抑制PI 3 K对乙醇心血管作用和心肌Akt磷酸化的影响。乙醇的血流动力学效应（BP、CO和SV降低）与心肌NOx和心肌p-nNOS和p-Akt表达的显著增加相关，而心肌p-eNOS保持不变。NPLA（2.5或12.5 μg/kg）预先抑制nNOS可减弱乙醇的血流动力学效应，并消除心肌NOx和心脏p-nNOS含量的相关增加。wortmannin（15 μg/kg）可降低乙醇的血流动力学效应和心肌p-Akt磷酸化的增加。另一方面，虽然eNOS抑制L-NIO（4或20 mg/kg）剂量依赖性衰减乙醇诱发的低血压，CO和SV的伴随减少保持不变。此外，选择性eNOS抑制揭示了显着增加TPR响应乙醇，这似乎抵消了减少CO。无论是NPLA或L-NIO改变血浆乙醇水平。这些发现暗示心肌PI 3 K/Akt/nNOS信号通路在降低雌性大鼠乙醇产生的BP和CO中起作用。
The mechanism by which ethanol reduces cardiac output (CO) and blood pressure (BP) in female rats remains unclear. We tested the hypothesis that enhancement of myocardial phosphatidylinositol 3-kinase (PI3K)/Akt signaling and related nNOS and/or eNOS activity constitutes a cellular mechanism for the hemodynamic effects of ethanol. We measured the level of phosphorylated eNOS (p-eNOS) and p-nNOS in the myocardium of ethanol (1 g/kg intragastric, i.g.) treated female rats along with hemodynamic responses (BP, CO, stroke volume, SV, total peripheral resistance, TPR), and myocardial nitrate/nitrite levels (NOx). Further, we investigated the effect of selective pharmacological inhibition of nNOS with Nω-propyl-L-arginine or eNOS with N5-(1-iminoethyl)-L-ornithine on cellular, hemodynamic and biochemical effects of ethanol. The effects of PI3K inhibition by wortmannin on the cardiovascular actions of ethanol and myocardial Akt phosphorylation were also investigated. The hemodynamic effects of ethanol (reductions in BP, CO, and SV) were associated with significant increases in myocardial NOx and myocardial p-nNOS and p-Akt expressions while myocardial p-eNOS remained unchanged. Prior nNOS inhibition by NPLA (2.5 or 12.5 μg/kg) attenuated hemodynamic effects of ethanol and abrogated associated increases in myocardial NOx and cardiac p-nNOS contents. The hemodynamic effects of ethanol and increases in myocardial p-Akt phosphorylation were reduced by wortmannin (15 μg/kg). On the other hand, although eNOS inhibition by L-NIO (4 or 20 mg/kg) dose-dependently attenuated ethanol-evoked hypotension, the concomitant reductions in CO and SV remained unaltered. Also, selective eNOS inhibition uncovered dramatic increases in TPR in response to ethanol, which appeared to have offset the reduction in CO. Neither NPLA nor L-NIO altered plasma ethanol levels. These findings implicate the myocardial PI3K/Akt/nNOS signaling in the reductions in BP and CO produced by ethanol in female rats.
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影响因子：
8.3
作者：
Sudhir, K;Esler, MD;Komesaroff, PA
通讯作者：
Komesaroff, PA
影响因子：
3.3
作者：
El-Mas, MM;Zhang, J;Abdel-Rahman, AA
通讯作者：
Abdel-Rahman, AA
影响因子：
12.3
作者：
El-Mas, MM;Abdel-Rahman, AA
通讯作者：
Abdel-Rahman, AA
DOI：
10.1111/j.1530-0277.1994.tb00891.x
发表时间：
1994-02-01
影响因子：
3.2
作者：
THOMAS, AP;ROZANSKI, DJ;RUBIN, E
通讯作者：
RUBIN, E
DOI：
10.1007/bf01960370
发表时间：
1979-01-01
期刊：
EXPERIENTIA
影响因子：
--
作者：
TURLAPATY, PDMV;ALTURA, BT;ALTURA, BM
通讯作者：
ALTURA, BM