In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 296, No. 3 ( 2009-03), p. L462-L469
Abstract:
The protective effects of nitric oxide (NO), a physiological activator of soluble guanylyl cyclase (sGC), have been reported in ischemia-reperfusion (I/R) syndrome of the lung. Therefore, we studied the effects of BAY 41-2272, a novel sGC stimulator, on I/R injury of the lung in an isolated intact organ model. Lung injury was assessed by measuring weight gain and microvascular permeability (capillary filtration coefficient, K fc ). Release of reactive oxygen species (ROS) into the perfusate was measured during early reperfusion by electron spin resonance (ESR) spectroscopy. Rabbit lungs were treated with BAY 41-2272, N G -monomethyl-l-arginine (l-NMMA), or NO to evaluate the effects on I/R-induced lung injury. In untreated lungs, a dramatic rise in K fc values and weight gain during reperfusion were observed, and these results were associated with increased ROS production. Both, BAY 41-2272 and l-NMMA significantly attenuated vascular leakage and suppressed ROS release. Additional experiments showed that BAY 41-2272 diminished PMA-induced ROS production by NADPH oxidase. A pharmacological inhibition of the enzyme with consequent reduction in ROS levels decreased I/R injury. NO had only marginal effect on I/R injury. Thus BAY 41-2272 protects against I/R-induced lung injury by interfering with the activation of NADPH oxidases.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.90377.2008
Language:
English
Publisher:
American Physiological Society
Publication Date:
2009
detail.hit.zdb_id:
1477300-4
SSG:
12
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