Amlodipine attenuates oxidative stress-induced hypertension.
BACKGROUND
Dihydropyridine Ca2+-blockers, frequently used as antihypertensive and antianginal agents, have been found to exert potent antioxidant and cytoprotective activities against free radical-mediated vascular injury.


METHODS
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 A2, 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.


RESULTS
Administration of BSO significantly increased BP, isoprostane, and thromboxane A2, whereas GSH, PGI2, and cAMP were reduced. When given alone, AMLOD alone reduced BP and the plasma levels of isoprostane and thromboxane A2, and elevated prostacyclin, nitric oxide, cGMP, and cAMP. When administered with BSO, AMLOD reversed the BSO-induced elevation of BP, isoprostane, and thromboxane A2 as well as the reduction in prostacyclin, cAMP, and cardiac GSH levels.


CONCLUSIONS
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.
Ganafa
Agaba A
AA
Department of Pharmacology/Toxicology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA.
Walton
Marcus
M
Eatman
Danita
D
Abukhalaf
Imad K
IK
Bayorh
Mohamed A
MA
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D011464:Epoprostenol / Q000097:blood; D005978:Glutathione / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000187:drug effects; D013929:Thromboxane B2 / Q000097:blood
D000959:Antihypertensive Agents; D017311:Amlodipine; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D013929:Thromboxane B2; D015237:Dinoprost; D011464:Epoprostenol; D000242:Cyclic AMP; D005978:Glutathione; D006152:Cyclic GMP