Acute cardiac allograft rejection in nitric oxide synthase-2(-/-) and nitric oxide synthase-2(+/+) mice: Effects of cellular chimeras on myocardial inflammation and

BACKGROUND: The contribution of nitric oxide synthase (NOS)-2 to myocardial inflammation and cardiomyocyte necrosis and apoptosis during allograft rejection was investigated through heterotopic cardiac transplantation in mice. METHODS AND RESULTS: In the first experiments, hearts from C3H donor mice were transplanted into NOS-2(-/-) and NOS-2(+/+) C57BL/6J.129J recipients. A second series of experiments included NOS-2(-/-) donor hearts transplanted into NOS-2(-/-) recipients and wild-type NOS-2(+/+) donor hearts transplanted into wild-type NOS-2(+/+) recipients. (All donors were C57BL/6J and recipients were C57BL/6J.129J.) In the first series of experiments, no significant differences were observed in allograft survival, rejection score, total number of apoptotic nuclei (TUNEL), total number of apoptotic cardiomyocytes, or graft NOS-2 mRNA and protein. Positive NOS-2 immunostaining occurred in endothelial cells and cardiomyocytes in the allografts; the inflammatory infiltrate was NOS-2 positive only when recipients were NOS-2(+/+). In the second series of experiments, cardiac allograft survival was significantly increased in the NOS-2(-/-) mice (26+/-13 versus 17+/-8 days, P