Influence of differing classes of antihypertensive agents on mesangial kinetics following partial renal ablation in rats.
Mesangial kinetics were studied in six groups of rats. Rats were either sham operated or were subjected to 1 1/3 nephrectomy (4/6 Nx). Each group was either untreated or was treated with enalapril (EN) or the drug regimen of hydralazine, hydrochlorothiazide, and reserpine (HHR). Four weeks after surgery rats were injected with iodinated aggregated bovine serum albumin (I-aggBSA) and mesangial localization quantified 2, 4, or 8 h later. Mesangial kinetics in untreated 4/6 Nx rats were characterized by accumulation of I-aggBSA to 4 h after injection with rapid clearance over the 4-8-h period; i.e. mesangial trafficking was increased following 4/6 Nx. Mesangial trafficking in 4/6 Nx rats treated with EN was reduced by virtue of lesser uptake of I-aggBSA at 4 h and retarded clearance over 4-8 h when compared with untreated 4/6 Nx animals. Treatment of 4/6 Nx rats with HHR maintained the increased trafficking observed in untreated 4/6 Nx rats. At 30 weeks untreated 4/6 Nx rats had severe albuminuria and glomerulosclerosis. Both indices of renal damage were significantly less in 4/6 Nx rats treated with enalapril. Treatment with HHR did not prevent albuminuria and had only limited effectiveness in preventing glomerulosclerosis. The different effects of EN and HHR on mesangial trafficking and glomerulosclerosis provide further evidence for a relationship between mesangial trafficking following partial renal ablation and subsequent development of glomerulosclerosis.
Odum
J
J
Renal Research Laboratories, School of Postgraduate Medicine, University of Keele, Stoke-on-Trent, UK.
Purkiss
J
J
Naish
P F
PF
D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D000959:Antihypertensive Agents / Q000145:classification / Q000494:pharmacology*; D001693:Biological Transport, Active; D004656:Enalapril / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism*; D006830:Hydralazine / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006984:Hypertrophy; D007678:Kidney Glomerulus / Q000473:pathology; D007700:Kinetics; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D006830:Hydralazine; D012710:Serum Albumin, Bovine; D004656:Enalapril; D012110:Reserpine