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- Title
Glomerulosclerosis and progression: Effect of subantihypertensive doses of α and β blockers.
- Authors
Amann, Kerstin; Koch, Andreas; Hofstetter, Jürgen; Gross, Marie-Luise; Haas, Christian; Orth, Stephan R.; Ehmke, Heimo; Rump, Lars Christian; Ritz, Eberhard
- Abstract
Glomerulosclerosis and progression: Effect of subantihypertensive doses of α and β blockers. Background. Uremia is characterized by inadequately increased sympathetic activity. Sympathetic overactivity is involved in the genesis of hypertension in uremia, but its potential role on progression has not been well investigated. To address this issue, the effect of subantihypertensive doses of an α blocker and a β blocker, and their combination on renal morphology and on albuminuria were investigated in the model of the subtotally nephrectomized rat. Methods. Male Sprague-Dawley rats were subjected to surgical ablation (SNX) or sham operation (sham). Three days after surgery groups were treated either with phenoxybenzamine (PBZ, 5 mg/kg body weight/day), metoprolol (MET, 150 mg/kg body weight/day) or their combination (PBZ 2.5 mg/kg body weight/day + MET, 50 mg/kg body weight/day). Renal morphology was evaluated after 12 weeks by quantitative histology, immunohistochemistry, and electron microscopy. Urine albumin excretion and kidney endothelin-1 (ET-1), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) mRNA expression were assessed. Results. Systolic blood pressure was significantly higher in all SNX groups compared with sham-operated controls with no difference in the SNX groups. The number of glomeruli per left kidney was reduced from 30,904 ± 3212 to 17,480 ± 2341 by SNX (-43.5%). Mean glomerular volume increased from 2.63 ± 0.7 in untreated sham operated to 4.11 ± 0.48 μm3 × 106 in untreated SNX (56.3%). The glomerulosclerosis index did not change in SNX + PBZ rats, but was significantly lower in SNX + MET (0.56 ± 0.14) and particularly SNX + PBZ + MET rats (0.49 ± 0.11) than in untreated SNX (0.74 ± 0.24). Glomerular capillary length density (LV) as a sensitive index of capillary obliteration was significantly lower in SNX...
- Subjects
ADRENERGIC alpha blockers; ADRENERGIC beta blockers; ALBUMINURIA
- Publication
Kidney International, 2001, Vol 60, Issue 4, p1309
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2001.00936.x