Captopril ameliorates myocarditis in acute experimental Chagas disease.
BACKGROUND
Captopril, an angiotensin-converting enzyme inhibitor, is commonly prescribed to patients with Chagas heart disease (CHD). There are few human studies and no animal studies on the effects of captopril in CHD. We investigated the effects of captopril on myocarditis and the host immune response to Trypanosoma cruzi in an experimental model of acute CHD.


RESULTS
A/J mice infected with Brazil strain of T cruzi developed acute myocarditis by day 21 after infection, consisting of severe focal inflammation, necrosis, fibrosis, and T cruzi pseudocysts. Administration of captopril (5 mg/L in the water) significantly reduced necrosis and fibrosis in infected mice. Increasing the captopril dose also led to a decrease in inflammation. Captopril did not affect overall mortality but did delay death while having no effect on parasitemia or cardiac parasite load. Treatment did not affect humoral immunity against T cruzi or cardiac myosin (autoimmunity) but did decrease delayed-type hypersensitivity responses against both antigens. Interestingly, increasing the dose of captopril induced mortality in infected mice in a dose-dependent manner. Mortality was apparently not due to T cruzi because neither parasitemia nor cardiac parasitosis was affected. The combination of captopril and infection may have impaired renal function because these mice had increased water consumption, decreased body mass, and increased serum BUN/creatinine ratio.


CONCLUSIONS
Captopril ameliorates the myocarditis associated with acute T cruzi infection.
Leon
Juan S
JS
Department of Pathology and the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave, Ward 6-175, Chicago, Ill 60611, USA.
Wang
Kegiang
K
Engman
David M
DM
D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D002216:Captopril / Q000627:therapeutic use*; D002598:Chagas Cardiomyopathy / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D006968:Hypersensitivity, Delayed / Q000175:diagnosis; D008297:Male; D051379:Mice; D009336:Necrosis; D018512:Parasitemia / Q000188:drug therapy; D016019:Survival Analysis; D014349:Trypanosoma cruzi / Q000276:immunology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000913:Antibodies, Protozoan; D002216:Captopril