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Role of Bradykinin in the Regulation of Endothelial Nitric Oxide Synthase Expression by Cardiovascular Drugs.

NO produced by eNOS plays important roles in the cardiovascular system. Alterations in eNOS activity and expression occur in various cardiovascular disorders and eNOS constitutes a therapeutic target. In addition to posttranslational modifications of eNOS that affect eNOS activity, transcriptional and post-transcriptional regulation of eNOS expression also controls eNOS-derived NO production. Bradykinin is an important determinant of vascular function and participates in the regulation of eNOS activity and expression. A number of currently used drugs or investigational molecules targeting specific ion channels, enzymes or receptors, including dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, statins, AT1 receptor blockers and angiotensin-(1-7), increase eNOS expression and activity. In this context, activation of bradykinin B2 receptors appears to be a common step for these drugs to promote eNOS expression, which certainly contributes to their therapeutic actions.

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