Carvedilol, a new beta-adrenoreceptor blocker, vasodilator and free-radical scavenger, exerts an anti-shock and endothelial protective effect in rat splanchnic ischemia and reperfusion.
Splanchnic artery occlusion (SAO) followed by reperfusion results in circulatory shock in which oxygen-derived free radicals play an important role. Carvedilol, a novel beta adrenoceptor antagonist and a vasodilator, has been recently shown to exert potent antioxidant effects in multiple cell model systems. In the present experiment, we investigated the effect of carvedilol on SAO shock. Pentobarbital-anesthetized rats were subjected to 60 min of SAO followed by 120 min of reperfusion. Administration of 1 mg/kg carvedilol 10 min before reperfusion prolonged survival time (P < .05) and attenuated the increases in tissue myeloperoxidase activities (P < .01) and hematocrits (P < .001). Moreover, carvedilol significantly preserved superior mesenteric artery endothelial function (P < .01). Similar protection was seen in SAO shock rats treated with the superoxide free-radical scavenger superoxide dismutase. Except for a moderate attenuation of an increase in hematocrits, protective effects were not seen in SAO shock rats treated with the prototypic beta blocker propranolol. These results indicate that in murine SAO shock, carvedilol affords significant protection, which may be achieved through maintenance of tissue blood perfusion, quenching of oxygen free radicals, preservation of vascular endothelial function, and inhibition of neutrophil-endothelial interaction and its resultant increased microvascular permeability.
Christopher
T A
TA
Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Lopez
B L
BL
Yue
T L
TL
Feuerstein
G Z
GZ
Ruffolo
R R
RR
Ma
X L
XL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006400:Hematocrit; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D012769:Shock / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D016166:Free Radical Scavengers; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D009195:Peroxidase; D013482:Superoxide Dismutase