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.
Zingarelli
B
B
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Caputi
A P
AP
Di Rosa
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013237:Stereoisomerism
D010656:Phenylephrine; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester