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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.
J Pharmacol Exp Ther. 1995 Apr; 273(1):64-71.JP

Abstract

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.

Authors+Show Affiliations

Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7714814

Citation

Christopher, T A., et al. "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." The Journal of Pharmacology and Experimental Therapeutics, vol. 273, no. 1, 1995, pp. 64-71.
Christopher TA, Lopez BL, Yue TL, et al. 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. J Pharmacol Exp Ther. 1995;273(1):64-71.
Christopher, T. A., Lopez, B. L., Yue, T. L., Feuerstein, G. Z., Ruffolo, R. R., & Ma, X. L. (1995). 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. The Journal of Pharmacology and Experimental Therapeutics, 273(1), 64-71.
Christopher TA, et al. 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. J Pharmacol Exp Ther. 1995;273(1):64-71. PubMed PMID: 7714814.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Christopher,T A, AU - Lopez,B L, AU - Yue,T L, AU - Feuerstein,G Z, AU - Ruffolo,R R,Jr AU - Ma,X L, PY - 1995/4/1/pubmed PY - 2001/3/28/medline PY - 1995/4/1/entrez SP - 64 EP - 71 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 273 IS - 1 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7714814/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_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&amp;pmid=7714814 DB - PRIME DP - Unbound Medicine ER -