We examined the interrelation between systemic hypertension, hyperlipidemia, and progressive renal injury in experimental glomerulonephritis. Induction of nephrotoxic serum nephritis in Sprague- Dawley rats led to systemic hypertension and hyperlipidemia. Four groups of rats were studied over a 16-week period: (1) untreated nephritic rats; (2) nephritic rats treated with hydralazine, reserpine, and lasix (AH); (3) nephritic rats treated with lovastatin (4 mg/kg) (Lova); and (4) nephritic rats treated with combined antihypertensive/lipid-lowering therapy (AH/Lova). Systolic blood pressure rose progressively in untreated rats (152±4 mm Hg at 16 weeks). Blood pressure was reduced by antihypertensive therapy (P<.001) (108±2 mm Hg in the AH group and [11±3 mm Hg in the AH/Lova group) but remained elevated in animals treated with lovastatin alone (P>.05) (156±3 mm Hg in the Lova group). Serum cholesterol rose progressively in untreated rats (3.70±0.85 mmol/L [143±33 mg/dL] at 16 weeks). The rise in serum cholesterol was prevented by lovastatin therapy (P<.001) (2.22±0.41 mmol/L [86±16 mg/dL] in the Lova group and 2.09±0.52 mmol/L [81±2 mg/dL] in the AH/Lova group) but not antihypertensive therapy (P>.05) (2.92±0.65 mmol/L [1113±25 mg/dL] in the AH group). Proteinuria was reduced by antihypertensive therapy (P<.001) and lipid-lowering therapy (P<.05) (16- week values: 1.069±0.167 g/d in untreated rats, 0.663±0.164 g/d in the Lova group, 0.392±0.051 g/d in the AH group, and 0.176±0.035 g/d in the AH/Lova group). Glomerular injury score was significantly reduced by antihypertensive therapy (P<.01) and lipid-lowering therapy (P<.05). Glomerular injury score was lowest in animals receiving combined therapy, reflecting an interaction between these therapies (P<.01) (untreated, 173±29; Lova, 128±24; AH, 111±22; AH/Lova, 48±11). Our results suggest that both hypertension and hyperlipidemia accelerate glomerular sclerosis in experimental glomerulonephritis and that combined therapy of these disorders may best limit progressive renal injury.
ASJC Scopus subject areas
- Internal Medicine