Reduction of bleomycin-induced sequestration of neutrophils and vascular injury in hamster lungs by nitroglycerin

Abstract

Neutrophil sequestration within the pulmonary microvasculature contributes to the pathogenesis of various types of lung injury. The present study was designed to test the hypothesis that nitroglycerin, a vasodilator, could decrease neutrophil sequestration within the hamster lung, and thus lead to reduction of bleomycin-induced lung inflammation and injury. Nitroglycerin in an ointment base or petroleum jelly was dermally applied twice daily to the backs of hamsters which were given a single dose of bleomycin or 0.9% NaCl intratracheally. Nitroglycerin significantly reduced the bleomycin-induced increase in neutrophil sequestration in the lungs as indicated by a decrease in the number of neutrophils in bronchoalveolar lavage fluid (BALF), and by both BALF and tissue myeloperoxidase activity. Similarly, nitroglycerin significantly attenuated bleomycin-induced increases in protein content and acid phosphatase activity in the BALF supernatant. There was a marginal, but nonstatistically significant, reduction of bleomycin-induced increases in lung hydroxyproline content and malondialdehyde production by nitroglycerin. It was concluded that nitroglycerin, acting presumably by inducing pulmonary vasodilation, caused a marked reduction in the bleomycin-induced neutrophil sequestration and thus offered protection against the vascular leakage and lung injury in the model.