DEXAMETHASONE PREVENTS VASCULAR FAILURE MEDIATED BY NITRIC-OXIDE IN HEMORRHAGIC-SHOCK

The involvement of L-arginine/nitric oxide (NO) pathway in the vascula r reactivity following hypovolemic hemorrhagic shock was studied in ma le anesthetized Wistar rats. Aortic rings from shocked rats showed a m arked hyporeactivity (p < .01) to phenylephrine (PE, 1 nM to 10 mu M), whereas the responsiveness to acetylcholine (ACh, 10 nM to 10 mu M) r emained unaffected. The response of these rings was restored to contro l values by N-gamma-nitro-L-arginine methyl ester (L-NAME, 10 mu M). D -NAME was without effect. L-Arginine (300 mu M), but not D-arginine, s ignificantly increased the vascular hyporeactivity of aortic rings fro m hemorrhagic shocked rats (p < .01), while it had no effect in rings from sham shocked rats. Dexamethasone (.1, 1, or 2 mg/kg), given intra venously 2 h before bleeding, significantly (p < .01) increased surviv al rate and reduced the severe hypotension due to hemorrhagic shock (p < .01). Additionally, aortic rings of hemorrhagic shocked rats pretre ated 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 ef fects in hemorrhagic shock by inhibiting NO synthesis.