Indomethacin, (-)-terbutaline (beta 2 agonist), and (+)-terbutaline in acute inflammation induced by repeated ischemia in hamster cheek pouch.
A mild and controlled acute inflammatory reaction in hamster cheek pouch was created without any exogenous, but rather by locally activated and liberated, mediators. A pressure of 60 mm Hg was applied to part of the everted cheek pouch eight times with a 10-min recovery period in between. The microvascular response was followed by intravital microscopy and the permeability changes were monitored with intravital fluoroscopy and intravenous FITC dextran (mol wt 150,000). The number of extravasated polymorphonuclear leukocytes (PMNLs) was calculated by a new, whole tissue, histological technique. In three experimental groups (-)-terbutaline (beta 2-receptor agonist) 0.05 mg/100 g body wt., (+)-terbutaline 0.05 mg/100 g body wt., and indomethacin 2 mg/100 g body wt. was given intravenously before pressure was applied. A fourth group, with no drug given, served as control. There was a rapid increase in the number of FITC dextran leakages and extravasated PMNLs in the control group. Indomethacin almost completely inhibited FITC dextran permeability and extravasation of PMNLs. The beta 2 agonist markedly diminished the number of FITC dextran leakages for 75 min. The number of extravasated PMNLs was also reduced. Treatment with (+)-terbutaline, which is supposed to have no beta 2-receptor effect, gave a slight reduction in number of FITC dextran leakages and almost a complete inhibition of PMNL extravasation. Thus we conclude that indomethacin is a very potent antiinflammatory agent even in the early phase of inflammation. (-)-Terbutaline diminished the inflammatory response, probably by preventing endothelial gap formation. (+)-Terbutaline prevented PMNL extravasation either by interaction with the PMNL itself or with the endothelium.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007511:Ischemia / Q000150:complications; D008297:Male; D008647:Mesocricetus; D009504:Neutrophils / Q000187:drug effects; D013237:Stereoisomerism; D013726:Terbutaline / Q000494:pharmacology*
D013726:Terbutaline; D007213:Indomethacin