Dexamethasone prevents vascular failure mediated by nitric oxide in hemorrhagic shock.

The involvement of L-arginine/nitric oxide (NO) pathway in the vascular reactivity following hypovolemic hemorrhagic shock was studied in male anesthetized Wistar rats. Aortic rings from shocked rats showed a marked hyporeactivity (p < .01) to phenylephrine (PE, 1 nM to 10 microM), whereas the responsiveness to acetylcholine (ACh, 10 nM to 10 microM) remained unaffected. The response of these rings was restored to control values by N gamma-nitro-L-arginine methyl ester (L-NAME, 10 microM). D-NAME was without effect. L-Arginine (300 microM), but not D-arginine, significantly increased the vascular hyporeactivity of aortic rings from hemorrhagic shocked rats (p < .01), while it had no effect in rings from sham shocked rats. Dexamethasone (.1, 1, or 2 mg/kg), given intravenously 2 h before bleeding, significantly (p < .01) increased survival rate and reduced the severe hypotension due to hemorrhagic shock (p < .01). Additionally, aortic rings of hemorrhagic shocked rats pretreated with dexamethasone exhibited a greater contractile response to PE when compared to aortic rings from vehicle-pretreated shocked rats (p < .01). These results suggest that dexamethasone exerts beneficial effects in hemorrhagic shock by inhibiting NO synthesis.