Beneficial effect of captopril on systemic lupus erythematosus-like disease in MRL lpr/lpr mice.
MRL lpr/lpr (MRL/l) mice exhibit a disease similar to systemic lupus erythematosus (SLE) in humans. To investigate the influence of antihypertensive treatment on this disease, four groups of MRL/l mice were treated with the angiotensin-converting enzyme inhibitor captopril (n = 25), with the sympathetic blocker bretylium (n = 15), and with cyclophosphamide (n = 10). Thirty-five mice did not receive any treatment and served as controls. Survival rate, blood pressure, incidence of proteinuria and hematuria, renal pathology, lymphoid hyperplasia and dermatitis were studied. The survival at the age of 36 weeks was significantly improved by captopril as compared to controls (60 vs. 25%, p = 0.035). The cyclophosphamide group showed no mortality at that time and the bretylium group did not differ from the control group. Captopril and bretylium reduced systolic blood pressure significantly while cyclophosphamide was without effect. Captopril and cyclophosphamide diminished significantly the glomerular damage with less proliferative changes and a decreased incidence of proteinuria. The bretylium-treated animals also exhibited an improved renal pathology index but they did not differ from the controls with respect to proteinuria and hematuria. Lymphoid hyperplasia and dermatitis were decreased only by captopril and cyclophosphamide. It is concluded that captopril improves survival in SLE disease of MRL/l mice, counteracting lymphoid hyperplasia, renal disease, dermatitis and decreasing arterial blood pressure.
Herlitz
H
H
Department of Nephrology, University of Göteborg, Sahlgrenska Sjukhuset, Sweden.
Tarkowski
A
A
Svalander
C
C
Volkmann
R
R
Westberg
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001949:Bretylium Compounds / Q000627:therapeutic use; D002216:Captopril / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D003872:Dermatitis / Q000517:prevention & control; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008181:Lupus Nephritis / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains
D001949:Bretylium Compounds; D003520:Cyclophosphamide; D002216:Captopril; C045166:bretylium