Resveratrol prevents endothelial dysfunction and aortic superoxide production after trauma hemorrhage through estrogen receptor-dependent hemeoxygenase-1 pathway.
OBJECTIVE
To determine whether resveratrol provides vasculoprotection in trauma-hemorrhaged animals and whether the effects are mediated via estrogen receptor-dependent hemeoxygenase-1.


METHODS
Prospective, multiexperimental, randomized, controlled studies.


METHODS
University research laboratory.


METHODS
Male Sprague-Dawley rats weighing 300-350 g.


METHODS
Male Sprague-Dawley rats underwent trauma hemorrhage (mean arterial pressure 40 mm Hg for 90 min, then resuscitation). Resveratrol (30 mg/kg) with or without an estrogen receptor antagonist (ICI 182,780), a hemeoxygenase enzyme inhibitor (chromium-mesoporphyrin), or vehicle was injected during resuscitation. At 24 hrs after trauma hemorrhage with resuscitation or sham operation, the animals were euthanized for further evaluation.


RESULTS
Acetylcholine-induced endothelium-dependent relaxation decreased, whereas nicotinamide adenine dinucleotide-stimulated superoxide radical production in the aorta and aortic p22phox, p47phox, gp91phox, NOX1, and NOX4 mRNA concentrations increased in trauma-hemorrhaged rats vs. sham rats. All altered parameters were normalized in resveratrol-treated trauma-hemorrhaged rats. Furthermore, there was a significant increase in hemeoxygenase-1 after trauma hemorrhage, and resveratrol treatment further increased hemeoxygenase-1 expression in trauma-hemorrhaged rats. However, administration of ICI 182,780 or chromium-mesoporphyrin abolished the resveratrol-induced prevention of shock-induced oxidative stress and endothelial damage. In the resveratrol-treated rats subjected to trauma hemorrhage, there were significant improvements in plasma aspartate aminotransferase and alanine aminotransferase levels, and mortality rate, and there was lesser damage in histology.


CONCLUSIONS
Resveratrol treatment prevented the overproduction of superoxide radical/NADPH oxidase expression and restored the trauma-hemorrhage-impaired endothelium-dependent relaxation via estrogen receptor-dependent stimulation of hemeoxygenase-1 expression.
Yu
Huang-Ping
HP
Department of Anesthesiology, Chang Gung Memorial Hospital, National Pingtung University of Science and Technology, Pingtung, Taiwan.
Hwang
Tsong-Long
TL
Hwang
Tsann-Long
TL
Yen
Chia-Hung
CH
Lau
Ying-Tung
YT
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D000077267:Fulvestrant; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006470:Hemorrhage / Q000503:physiopathology*; D049449:Luminescence; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*
D000975:Antioxidants; D008652:Mesoporphyrins; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D013267:Stilbenes; C427471:chromium mesoporphyrin; D013481:Superoxides; D000077267:Fulvestrant; D004958:Estradiol; D051547:Heme Oxygenase-1; D000077185:Resveratrol