Effect of a BLT receptor antagonist in a model of severe ischemia and reperfusion injury in the rat.
Pharmacological strategies which limit neutrophil recruitment may also limit the damage induced by the reperfusion of an ischemic vascular territory. In the present study, we have investigated the effects of the BLT receptor antagonist, CP-105,696 ((+)-1-(3S,4R)-[3-(4-phenyl-benzyl)-4-hydroxy-chroman-7-yl]-cyclopentane carboxylic acid), on the local, remote and systemic inflammatory changes observed during severe intestinal ischemia (120 min) and reperfusion (120 min) injury. The post-ischemic treatment with CP-105,696 (3 mg/kg) virtually abolished the increase in vascular permeability, but not neutrophil accumulation, in the intestine and lungs. CP-105,696 partially inhibited the reperfusion-induced neutropenia, but failed to affect intestinal haemorrhage or lethality. CP-105,696 had no inhibitory effect on the local and systemic increases in the concentrations of tumour necrosis factor (TNF-alpha), interleukin-1 beta and interleukin-10, but markedly suppressed interleukin-6. Overall, our results show that activation of BLT receptor plays a minor role in the local, remote and systemic injuries following severe ischemia and reperfusion in rats.
Souza
Danielle G
DG
Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciencias Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627-Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
Pinho
Vanessa
V
Cassali
Giovanni D
GD
Poole
Stephen
S
Teixeira
Mauro M
MM
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002264:Carboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000187:drug effects; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D001578:Benzopyrans; D002264:Carboxylic Acids; D007375:Interleukin-1; D015850:Interleukin-6; D018102:Receptors, Leukotriene B4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C089698:CP 105696