I. Shou et al., EFFECTS OF ANTIHYPERTENSIVE DRUGS ON ANTIOXIDANT ENZYME-ACTIVITIES AND RENAL-FUNCTION IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS, The American journal of the medical sciences, 314(6), 1997, pp. 377-384
The reactive oxygen species has been proposed as a key mediator of the
progression of renal injury associated with essential hypertension. A
mong the defense systems operating against the reactive oxygen species
, superoxide dismutase, glutathione peroxidase, and catalase are the m
ost important antioxidant enzymes (AOEs). In the present study, systol
ic blood pressure, renal function (creatinine clearance, urinary album
in, and N-acetyl-beta D-glucosaminidase excretion), renal intrinsic AO
E 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-captop
ril, 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 rese
rpine)-on renal function, renal tissue, AOE activities, and renal hist
opathologic abnormalities were evaluated in stroke-prone spontaneously
hypertensive rats. Renal function and AOE activities were lower in th
e stroke-prone spontaneously hypertensive rats than in the Wistar Kyot
o rats. Normalization of systolic blood pressure using the antihyperte
nsive drugs improved renal function and produced a nonuniform alterati
on in renal AOEs; only glutathione peroxidase activity increased signi
ficantly with the use of all three drug regimens. The mild renal histo
pathologic 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.