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Vascular arginase contributes to arteriolar endothelial dysfunction in a rat model of hemorrhagic shock.
- Source :
-
The Journal of trauma [J Trauma] 2010 Aug; Vol. 69 (2), pp. 384-91. - Publication Year :
- 2010
-
Abstract
- Background: Hemorrhagic shock causes hypoperfusion of peripheral tissues and promotes endothelial dysfunction, which may lead to further tissue injury. Trauma increases extrahepatic activity of arginase, an enzyme which competes for l-arginine with nitric oxide synthase, and plays a key role in the development of endothelial dysfunction during aging, hypertension, and diabetes. However, the role of arginase in hemorrhage-induced endothelial dysfunction has not been studied. This study tests the hypothesis that arginase inhibition improves endothelial function after hemorrhage.<br />Methods: Male Sprague-Dawley rats were implanted with indwelling arterial catheters for blood pressure measurements and blood removal. Awake animals were subjected to a 45% fixed volume controlled hemorrhage and blood pressure was monitored. Unbled rats served as controls. Skeletal muscle arterioles were isolated 24 hours after hemorrhage and cannulated in a pressure myograph system. To study endothelial function, arterioles were exposed to constant midpoint, but altered endpoint pressures, to establish graded levels of luminal flow and internal diameter was measured.<br />Results: Hemorrhage lowered mean arterial pressure that spontaneously recovered to 78% and 88% of baseline in 2 hours and 20 hours, respectively. Vascular arginase II and blood glucose levels were elevated, whereas hemoglobin and insulin levels were decreased 24 hours after blood loss. In posthemorrhage arterioles, flow-induced dilation was abolished. Acute in vitro treatment with an inhibitor of arginase, N-hydroxy-nor-l-arginine, restored flow-induced dilation to unbled control levels. Similarly, the arginase and nitric oxide synthase substrate, l-arginine, but not the inactive isomer, d-arginine, restored flow-induced dilation.<br />Conclusions: These results indicate that arginase contributes to endothelial dysfunction in resistance vessels after significant hemorrhage.
- Subjects :
- Animals
Arginase antagonists & inhibitors
Arginine metabolism
Blood Flow Velocity
Disease Models, Animal
Enzyme Inhibitors pharmacology
Male
Random Allocation
Rats
Rats, Sprague-Dawley
Risk Factors
Vascular Resistance drug effects
Vascular Resistance physiology
Arginase metabolism
Endothelium, Vascular enzymology
Nitric Oxide Synthase metabolism
Shock, Hemorrhagic enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-8809
- Volume :
- 69
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of trauma
- Publication Type :
- Academic Journal
- Accession number :
- 20699748
- Full Text :
- https://doi.org/10.1097/TA.0b013e3181e771a3