B1 and B2 antagonists and bradykinin-induced blood flow in rat skin inflammation

Objective and design: The aim of the present study was to examine the contribution of the two kinin receptors B-1 and B-2 to the increased blood flow observed in response to bradykinin (BK) in a blister model under different injury conditions. Material: Young male Sprague-Dawley rats weighing 250-350 g were used. Methods: A vacuum-induced blister was raised in the rat hind paw and blood flow measured in the superfused blister base under four different conditions including, early phase acute injury; late phase acute injury; recurrent injury and early phase acute injury in the setting of chronic nerve damage. BK (10 muM) was superfused alone, or in the presence of the B-1 antagonist DesArg(9)Leu(8)BK (DALBK), (10 nM) and/or the B-2 antagonist [D-Arg,Hyp(3),Thi(5) D-Tic(7),Oic(8)] Bradykinin (HOE 140) (10 nM). Results: HOE 140 significantly inhibited the BK response in all models. Significant inhibition of BK-induced vasodilatation by DALBK was only observed in the late phase acute and recurrent injury models. Conclusions: The results suggest that the involvement of the inducible B-1 receptor in skin inflammation site is related to the site, duration and recurrence of the injury condition.