Controversial Effect of Ethanol Irrespective of Kinases Inhibition on the Agonist-dependant Vasoconstriction
Overview
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The present study was undertaken to determine whether ethanol influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Ethanol significantly inhibited thromboxane A2 mimetic-induced contraction with intact endothelial function, but there was no relaxation on thromboxane A2 mimetic U-46619-induced contraction irrespective of endothelium suggesting that the pathway such as Rho-kinase activation, Ca(2+) entry or thin filament regulation was not affected. In addition, ethanol didn't decrease thromboxane A2 mimetic-induced increase of phospho-myosin phosphatase targeting subunit protein 1 (pMYPT1) or pERK1/2. Interestingly, ethanol didn't inhibit significantly phorbol ester-induced contraction in denuded muscles suggesting that thin filament regulation is less important on the ethanol-induced regulation in the muscle than endothelial NO synthesis. In conclusion, this study provides the evidence and possible related mechanism concerning the effect of ethanol on the agonist-dependent contraction in rat aortic rings with regard to endothelial function.
Lee S, Shnitko T, Hsu L, Broadwater M, Sardinas M, Wang T Addict Neurosci. 2023; 7.
PMID: 37576436 PMC: 10421607. DOI: 10.1016/j.addicn.2023.100105.