Effect of losartan on oxidative stress-induced hypertension in Sprague-Dawley rats.
BACKGROUND
Hypertension induced by oxidative stress has been demonstrated in normal rats. In the current study, we investigated the effect of the oral AT(1) receptor blocker losartan (10 mmol/kg/day) on oxidative stress, induced by glutathione (GSH) depletion (using buthionine-sulfoximine, BSO, 30 mmol/L/day in the drinking water), in Sprague-Dawley rats.


METHODS
Mean arterial pressure (MAP) was measured by tail-cuff plethysmography and the plasma levels of total 8-isoprostane, nitric oxide, prostacyclin, thromboxane A(2), angiotensin II, aldosterone, and aortic cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were determined by enzyme immunoassay. Plasma, heart, and kidney GSH were analyzed by high-performance liquid chromatography. Aortic and renal superoxide production was determined by fluorescence spectrometry.


RESULTS
In the BSO-treated group, MAP, angiotensin II, isoprostane, thromboxane A(2), and superoxide were elevated; whereas prostacyclin, GSH, cAMP, and cGMP were reduced, compared to control. Losartan alone reduced MAP, and increased renal GSH, plasma nitric oxide, angiotensin II, aldosterone, and aortic cGMP. When administered concurrently with BSO, losartan reversed the BSO-induced elevation of MAP, superoxide, and thromboxane A(2) as well as the reduction in prostacyclin and aortic cAMP levels, but did not significantly alter the reduction in GSH or the elevation in angiotensin II and aldosterone.


CONCLUSIONS
Losartan attenuates BSO-induced hypertension, which appears to be mediated, in part, by angiotensin II and the prostanoid endothelium-derived factors.
Bayorh
Mohamed A
MA
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA. bayorh@msm.edu
Ganafa
Agaba A
AA
Socci
Robin R
RR
Eatman
Danita
D
Silvestrov
Natalia
N
Abukhalaf
Imad K
IK
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001011:Aorta / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D011464:Epoprostenol / Q000097:blood; D028441:F2-Isoprostanes / Q000097:blood; D005978:Glutathione / Q000097:blood / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013928:Thromboxane A2 / Q000097:blood; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D015415:Biomarkers; D004791:Enzyme Inhibitors; D028441:F2-Isoprostanes; D013481:Superoxides; D000804:Angiotensin II; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D000450:Aldosterone; D019328:Buthionine Sulfoximine; D013928:Thromboxane A2; D015237:Dinoprost; D011464:Epoprostenol; D000242:Cyclic AMP; D005978:Glutathione; D006152:Cyclic GMP; D019808:Losartan