Alteration of the granulomatous response in murine schistosomiasis by the chronic administration of captopril, an inhibitor of angiotensin-converting enzyme.
Captopril (SQ 14225) is an inhibitor of angiotensin I-converting enzyme (ACE). Mice with schistosomiasis form granulomas in the liver and intestines that have high ACE activity. We determined whether chronic oral captopril administration would alter the granulomatous response. Infected mice treated with captopril had a dose-dependent decrease in liver granuloma size. Chronic peroral administration of drug induced a sustained decrease in granuloma ACE activity and size which was reversible upon drug withdrawal. The drug was most effective during the acute phase of infection. Granuloma size in the colon, ileum, and ileal Peyer's patches was also decreased by treatment. Ileal granulomas were affected the least. Liver, colon, ileum, and ileal Peyer's patches demonstrated natural differences in size of response to schistosome eggs. Synchronous hypersensitivity granulomas, containing no ACE activity, were generated by the pulmonary embolization of methylated bovine serum albumin-coated, Sepharose beads into sensitized mice. Captopril treatment did not affect the size of these lesions. Sustained improvements in portal pressure, body and liver weight, and water consumption were seen in treated mice. We conclude that captopril induces sustained suppression of the granulomatous response in schistosome-infected mice, which results in decreased morbidity. Circumstantial evidence suggests that captopril influences inflammation through the competitive inhibition of ACE.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006099:Granuloma / Q000188:drug therapy; D008109:Liver Diseases, Parasitic / Q000188:drug therapy; D051379:Mice; D008808:Mice, Inbred CBA; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives*; D012552:Schistosomiasis / Q000188:drug therapy*; D012710:Serum Albumin, Bovine
D000806:Angiotensin-Converting Enzyme Inhibitors; D012710:Serum Albumin, Bovine; D011392:Proline; D002216:Captopril; D007703:Peptidyl-Dipeptidase A