Effects of antihypertensive agents on blood pressure and the progress of renal failure in partially nephrectomized spontaneously hypertensive rats.
The purpose of this study was to investigate the effects of antihypertensive agents on blood pressure and the development of glomerular changes in salt-loaded, 5/6 nephrectomized spontaneously hypertensive rats (SHR). Thirty-two spontaneously hypertensive rats with 5/6 nephrectomy were divided into 4 groups: a control group (N = 8), and group treated with 10 mg/kg/day trichlormethiazide. (N = 8), 30 mg/kg/day captopril (N = 8), and 200 mg/kg/day nicardipine (N = 8). Each of these antihypertensive drugs was added to the drinking water for 10 weeks and the rats were given the drugs and a high-salt diet (5% NaCl). During the experiment, body weight and systolic blood pressure were measured every 2 weeks. At the end of the study, blood was collected for determination of serum creatinine, blood urea nitrogen, serum protein, serum sodium and potassium, and plasma renin activity and aldosterone concentration. Also renal tissues were obtained for light and electron microscopic examination at the end of the study. Systolic blood pressure in 5/6 nephrectomized SHR loaded with a high salt was significantly reduced by administration of trichlormethiazide (155 +/- 12 versus 204 +/- 12 mm Hg), but not by administration of either captopril or nicardipine. However, levels of serum creatinine were not significantly elevated in rats treated with captopril and nicardipine (control: 0.93 +/- 0.11 mg/dl, captopril: 0.62 +/- 0.01 mg/dl, nicardipine: 0.55 +/- 0.05 mg/dl). In contrast to changes in blood pressure, marked glomerular sclerosis with hyalinosis, which was found in the control group was not ameliorated by treatment with trichlormethiazide. However, these changes were not observed in rats treated with either captopril or nicardipine in spite of the absence of a prominent fall in blood pressure. These data suggest that captopril and nicardipine ameliorated glomerular injury regardless of the level of systolic blood pressure through the direct and/or indirect actions on the glomerulus.
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
H
H
Katsumata
H
H
Suzuki
A
A
Ohishi
H
H
Nakamoto
T
T
Saruta
H
H
Sakaguchi
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology*; D009392:Nephrectomy / Q000379:methods; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D014237:Trichlormethiazide / Q000494:pharmacology*
D000959:Antihypertensive Agents; D002216:Captopril; D009529:Nicardipine; D014237:Trichlormethiazide