Beneficial effect of nifedipine and moxonidine on glomerulosclerosis in spontaneously hypertensive rats. A micromorphometric study.
The effect of calcium channel blockers on the development of glomerulosclerosis and progression of renal failure in different models of renal injury is still controversial. We compared the effects of blood pressure lowering with high doses of nifedipine (27 mg/kg body weight/day) and with the sympatholytic agent moxonidine (8 mg/kg body weight/day) in 6-month-old male spontaneously hypertensive rats (SHRsp). As controls we studied untreated hypertensive SHRsp and normotensive Wisfar-Kyoto rats (WKY). After 3 months of treatment, left ventricular (LV) weight and systolic blood pressure (tail plethysmography) were lower in both treated groups (144 +/- 21.4 mm Hg and 144 +/- 13.5 mm Hg v 193 +/- 38.6 mm Hg in untreated SHRsp), but remained higher than in WKY (116 +/- 16.0 mm Hg). Stereological analysis of perfusion fixed kidneys showed an unchanged total volume of cortex and medulla, but a higher mean glomerular volume in nifedipine treated SHRsp. The glomerulosclerosis index was similarly reduced by both antihypertensive agents (92.8 +/- 68.1 in untreated SHRsp v 27.2 +/- 12.9 and 18.2 +/- 9.8 in the two treatment groups, respectively). This was accompanied by a similar reduction of total cortical arterial wall volume (from 36.3 +/- 16.5 mm3 to 18.9 +/- 2.53 and 15.3 +/- 2.53 mm3, respectively) and by reduction of tubular atrophy or interstitial fibrosis, respectively. In this model nifedipine lowered blood pressure and inhibited development of glomerulosclerosis to the same extent as a sympatholytic agent. This was accompanied by increased glomerular volume and filtration area in nifedipine treated animals.
Irzyniec
T
T
Department of Pathology, Ruperto Carola University of Heidelberg, Germany.
Mall
G
G
Greber
D
D
Ritz
E
E
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001808:Blood Vessels / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation
D000959:Antihypertensive Agents; D007093:Imidazoles; C043482:moxonidine; D009543:Nifedipine