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Trypanosoma cruzi infection results in an increase in myocardial NO and intense inflammation. NO modulates the T. cruzi–induced myocardial inflammatory reaction. NO synthase (NOS)1-, NOS2-, and NOS3-null mice were infected with T. cruzi (Brazil strain). Infected NOS1-null mice had increased parasitemia, mortality, and left ventricular inner diameter (LVID). Chronically infected NOS1- and NOS2-null and wild-type mice (WT) exhibited increased right ventricular internal diameter (RVID), although the fold increase in the NOS2-null mice was smaller. Infected NOS3-null mice exhibited a significant reduction both in LVID and RVID. Reverse transcriptase-polymerase chain reaction showed expression of NOS2 and NOS3 in hearts of infected NOS1-null and WT mice, whereas infected NOS2-null hearts showed little change in expression of other NOS isoforms. Infected NOS3-null hearts showed an increase only in NOS1 expression. These results may indicate different roles for NOS isoforms in T. cruzi–induced cardiomyopathy.
Received November 5, 2008. Accepted for publication January 20, 2009.
Acknowledgment: The authors thank Stephen M. Factor for help with histopathology studies.
Financial support: These studies were supported by NIH Grants AI-062730 (LAJ), AI-052739 and AI-76248 (HBT), and HL-73732 (HBT), AHA SDG 0735252N (SM), and the Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES).
* Address correspondence to Herbert B. Tanowitz, Departments of Pathology and Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. E-mail: tanowitz{at}aecom.yu.edu
Authors addresses: Jorge L. Durand, Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, MRRC 301, Bronx, NY 10461, Tel: 718-430-3257, Fax: 718-430-8819. Shankar Mukherjee, Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, Tel: 718-430-3342, Fax: 718-430-8543. Fernando Commodari, R&D Department, Collagen Matrix, 509 Commerce Street, Franklin Lakes, NJ 07417, Tel: 201-405-1477 ext. 206, Fax: 201-405-1355. Andrea P. De Souza, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil, E-mail: andrea{at}ioc.fiocruz.br. Dazhi Zhao, Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, Tel: 718-430-3342, Fax: 718-430-8543. Fabiana S. Machado, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte MG, Brazil, Tel: 55-31-3409-2510, E-mail: machadofs{at}icb.ufmg.br. Herbert B. Tanowitz, Departments of Pathology and Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, Tel: 718-430-3342, Fax: 718-430-8543. Linda A. Jelicks, Department of Physiology and Biophysics, Albert Einstein College of Medicine, MRRC Building Room 301, 1300 Morris Park Avenue, Bronx, New York 10461, Tel: 718-430-2722, Fax: 718-430-8819.
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