enalapril and Granuloma

The successful management of cranial vena cava syndrome with suspected secondary chylothorax due to mediastinal cryptococcal granuloma in a 4-year-old male domestic shorthair cat is described. Treatment included long-term antifungal medication, short-term corticosteroids, intermittent thoracocentesis, rutin, octreotide, and enalapril.

Topics: Animals; Antifungal Agents; Antihypertensive Agents; Cat Diseases; Cats; Chylothorax; Cryptococcosis; Enalapril; Fluconazole; Granuloma; Ketoconazole; Male; Rutin; Superior Vena Cava Syndrome; Vena Cava, Superior

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Dermatitis, Exfoliative; Drug Eruptions; Enalapril; Granuloma; Humans; Hypertension; Male

Topics: Adult; Aged; Angioedema; Cheilitis; Dairy Products; Drug Hypersensitivity; Enalapril; Female; Food Hypersensitivity; Gingival Hyperplasia; Gingivitis; Granuloma; Humans; Hypersensitivity; Melkersson-Rosenthal Syndrome; Mouth Diseases; Pesticides; Spices

Systemic infection with Histoplasma capsulatum induced a granulomatous inflammatory response in the lymphoreticular organs of C57BL/6 mice that was associated with elevated levels of angiotensin-converting enzyme (ACE) in the spleens. To determine the influence of ACE on the granulomatous response, either captopril or MK 421, two inhibitors of ACE, were administered intraperitoneally to mice 6 h after intravenous injection of H. capsulatum and then daily for 1 week. Each ACE inhibitor sharply reduced ACE activity in the spleens of infected mice. Both drugs worsened the clinical severity of infection and significantly increased the growth of H. capsulatum in livers and spleens of mice infected for 1 week. The histopathological changes in mice given captopril were more severe, with massive infiltrates of macrophages in proximity to large aggregates of yeasts. Conversely, the administration of captopril for 2 weeks during the resolving phases of infection did not slow the healing of the granulomatous lesions, nor did it provoke a relapse of infection. Captopril did not promote the growth of H. capsulatum in artificial medium. This drug was not cytotoxic to peripheral blood leukocytes or to splenic leukocytes from normal and infected mice. Administration of captopril to normal mice for 1 week did not depress the response of splenocytes of concanavalin A or to phytohemagglutinin, nor did it diminish delayed-type hypersensitivity responses in vivo. Finally, captopril did not augment the growth of H. capsulatum within macrophages. Our results suggest that ACE may participate in the regulation of the granulomatous inflammatory response to H. capsulatum and that ACE inhibition impairs the protective effects of granulomatous inflammation during acute H. capsulatum infection.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Dipeptides; Enalapril; Granuloma; Histoplasma; Histoplasmosis; Hypersensitivity, Delayed; Inflammation; Liver; Lymphocyte Activation; Macrophages; Male; Mice; Mice, Inbred C57BL; Peptidyl-Dipeptidase A; Proline; Spleen

Angiotensin I (AI) and angiotensin II/III (AII/III) were detected by radioimmunoassay in homogenates of isolated liver granulomas from mice infected for 8 wk with Schistosoma mansoni. Angiotensin I converting enzyme (ACE) activity, which could be completely inhibited by captopril, a specific ACE inhibitor, was also present as determined by radioassay. Spontaneous angiotensin I-generating activity was detected in homogenates that received supplemental angiotensinogen (protein renin substrate). This activity was partly inhibited by pepstatin, an acid protease inhibitor, indicating the presence of angiotensinogenase(s). Trypsinization of homogenates resulted in some AI generation, which suggests that homogenates had AI precursor. Treatment of infected mice with MK421, another specific ACE inhibitor, decreased granuloma ACE activity and AII content and size. AII, and to a lesser extent AIII, inhibited mouse peritoneal macrophage migration in an in vitro assay. These data support the contention that components of the angiotensin system are in the granuloma and may serve a function in regulation of the inflammation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Angiotensins; Animals; Cell Migration Inhibition; Dipeptides; Enalapril; Endopeptidases; Female; Granuloma; Macrophages; Mice; Mice, Inbred CBA; Oligopeptides; Peptidyl-Dipeptidase A; Schistosoma mansoni; Schistosomiasis; Teprotide