Dihydropyridine Ca 2+-blockers, frequently used as antihypertensive and antianginal agents, have been found to exert potent antioxidant and cytoprotective activities against free radical-mediated vascular injury. In the current study we examined the effect of amlodipine (AMLOD) on oxidative stress-induced hypertension in Sprague-Dawley rats administered buthionine-sulfoximine (BSO), a glutathione (GSH) synthase inhibitor, in the drinking water. The control animals received drug-free water. Blood pressure (BP) was measured by tail-cuff plethysmography. Plasma levels of total 8-isoprostane, thromboxane A 2, prostacyclin, nitric oxide, and aortic cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were determined by enzyme immunoassay. Plasma, kidney, and heart GSH were analyzed by high-performance liquid chromatography. Administration of BSO significantly increased BP, isoprostane, and thromboxane A 2, whereas GSH, PGI 2, and cAMP were reduced. When given alone, AMLOD alone reduced BP and the plasma levels of isoprostane and thromboxane A 2, and elevated prostacyclin, nitric oxide, cGMP, and cAMP. When administered with BSO, AMLOD reversed the BSO-induced elevation of BP, isoprostane, and thromboxane A 2 as well as the reduction in prostacyclin, cAMP, and cardiac GSH levels. The antihypertensive effect of amlodipine involves a reduction in oxidative stress, which appears to be mediated in part by the prostanoid endothelium-derived factors and nitric oxide. © 2004 American Journal of Hypertension, Ltd.
Ganafa, A. A., Walton, M., Eatman, D., Abukhalaf, I. K., & Bayorh, M. A. (2004). Amlodipine attenuates oxidative stress-induced hypertension. American Journal of Hypertension, 17(9), 743–748. https://doi.org/10.1016/j.amjhyper.2004.05.013