To evaluate the possible enhancing effect of hypertension on the clinical and morphologic features of glomerulonephritis, two-kidney clip hypertension (CH) was superimposed on a mild form of nephrotoxic serum nephritis (NSN) in female Sprague-Dawley rats. The following parameters were assessed regularly over a 6-month period: blood pressure (BP), heart weight, proteinuria (UpV), and renal morphology. Blood pressures and heart weights were increased equally in clip hypertension and in nephrotoxic serum nephritis combined with clip hypertension. While only moderate proteinuria occurred in nephrotoxic serum nephritis (49 ± 28 mg/24 hr) or clip hypertension (40 ± 22 mg/24 hr) alone, the superimposition of clip hypertension on nephrotoxic serum nephritis resulted in heavy proteinuria (161 ± 36 mg/24 hr) (P < 0.001) after 5 months of hypertension. Glomerular histology in nephrotoxic serum nephritis showed infrequent focal and segmental proliferation and minimal sclerosis; vessels were normal. Clip hypertension was characterized by infrequent and mild vascular sclerosis and glomerular proliferation and sclerosis. Severe glomerular endo- and extracapillary proliferation and widespread glomerular and vascular sclerosis occured in the majority of rats when nephrotoxic serum nephritis was combined with clip hypertension. The data demonstrate that clip hypertension enhances glomerular proliferation and sclerosis and results in the development of vascular sclerosis in experimental nephritis.
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