Effects of antihypertensive drugs on antioxidant enzyme activities and renal function in stroke-prone spontaneously hypertensive rats

Abstract

The reactive oxygen species has been proposed as a key mediator of the progression of renal injury associated with essential hypertension. Among the defense systems operating against the reactive oxygen species, superoxide dismutase, glutathione peroxidase, and catalase are the most important antioxidant enzymes (AOEs). In the present study, systolic blood pressure, renal function (creatinine clearance, urinary albumin, and N-acetyl-beta D-glucosaminidase excretion), renal intrinsic AOE activities, and renal histopathology were determined in stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats. The effects of a 20-week treatment using three antihypertensive drug regimens--captopril, a sulfhydryl-containing angiotensin-converting enzyme inhibitor; temocapril, a potent, non-sulfhydryl-containing angiotensin-converting enzyme inhibitor prodrug; and a conventional triple drug combination that includes a vasodilator (hydralazine, hydrochlorothiazide and reserpine)--on renal function, renal tissue, AOE activities, and renal histopathologic abnormalities were evaluated in stroke-prone spontaneously hypertensive rats. Renal function and AOE activities were lower in the stroke-prone spontaneously hypertensive rats than in the Wistar Kyoto rats. Normalization of systolic blood pressure using the antihypertensive drugs improved renal function and produced a nonuniform alteration in renal AOEs; only glutathione peroxidase activity increased significantly with the use of all three drug regimens. The mild renal histopathologic abnormality in stroke-prone spontaneously hypertensive rats was not altered by drug treatment. The improvement in renal function may be related to an increase in glutathione peroxidase activity, but no correlation was seen between renal function changes and alteration in activities of superoxide dismutase or catalase.