The role of hypertension in the vascular disease and myocardial infarcts associated with murine systemic lupus erythematosus

Abstract

The several kinds of mice that spontaneously develop acute systemic lupus erythematosus (SLE)—BXSB males, MRL/I males and females, and (NZB x W)F₁ females—have a 15–20% incidence of degenerative vascular disease (DVD) and myocardial infarcts (MI) in which the affected coronaries contain deposits of immunoreactants, presumably in the form of immune complexes. Among the F₁ hybrid crosses of SLE mice, only the (NZW x BXSB)F₁, (W x B)F₁ male has a significantly higher incidence of DVD/MI (80%). Search for possible causes of this high incidence of myocardial infarcts revealed several unique features of this mouse: hypertension, thrombocytosis, and early onset of circulating immune complexes and glomerulonephritis. Our attempts to prevent this DVD/MI focused on: reduction of hypertension, prevention of thrombosis, and immunosuppression. Immunosuppression by Cytoxan resulted in almost complete prevention of both the SLE disease and DVD/MI. Administration of bretylium, an antihy-pertensive and anti-arrhythmic agent, resulted in reduction of blood pressure and the severities of glomerulonephritis, DVD, and MI; phritis, DVD, and MI; it also slightly reduced the levels of circulating immune complexes and leukocytosis. Of the 4 antithrombotic agents used, only aspirin showed some reduction in the incidence of DVD/MI and delay of glomerulonephritis-associated mortality.