Combined Antihypertensive and Lipid-Lowering Therapy in Experimental Glomerulonephritis

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 23; no. 1; pp. 92 - 95
• Main Authors: Rubin, Rhonda, Silbiger, Sharon, Sablay, Leonarda, Neugarten, Joel
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.01.1994; Hagerstown, MD Lippincott
• Subjects: Animals; Antihypertensive agents; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Cardiovascular system; Cholesterol - blood; Glomerulonephritis - blood; Glomerulonephritis - complications; Glomerulonephritis - drug therapy; Glomerulosclerosis, Focal Segmental - prevention & control; Hyperlipidemias - complications; Hyperlipidemias - drug therapy; Hypertension - complications; Hypertension - drug therapy; Lovastatin - therapeutic use; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Hypertension; Glomerulonephritis; Drug combination; Rat; Rodentia; Cardiovascular disease; Metabolic diseases; Lipids; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Animal; Antihypertensive agent; Complication; Hyperlipemia; Antilipemic agent
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.23.1.92

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/lipidlowering 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 mmHg in the AH group and 111±3 mm Hg in the AH/Lova group) but remained elevated in animals treated with lovastatin alone (P>.05) (156±3 mmHg 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 [8 6±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 [113±25 mg/dL] in the AH group). Proteinuria was reduced by antihypertensive therapy (P<.001) and lipid-lowering therapy (P<.05) (16-week values1.069±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.