The modulatory effects of Bradykinin B 1 and B 2 receptor antagonists upon viscero-visceral hyper-reflexia in a rat model of visceral hyperalgesia

Abstract

This study assessed the relative involvement of the two bradykinin (Bk) receptors (B 1 and B 2) in the viscero-visceral hyper-reflexia (VVH) and plasma extravasation observed in an animal model of cystitis. The effects of the competitive receptor antagonists des-Arg 9[Leu 8]-Bk (B 1) and HOE 140 (B 2) were tested both in prophylactic (pre-inflammation administration) and therapeutic (post-inflammation administration) scenarios. Compared with control animals, des-Arg 9[Leu 8]-Bk had no effect on the hyper-reflexic response of the bladder to inflammation unless it was administered 5 h after inflammation. However, HOE 140 was able to attenuate the inflammation-induced viscero-visceral hyper-reflexia (VVH) at doses of 1 mg/kg, 2 mg/kg and 7.5 mg/kg. This effect was apparent whether the drug was administered before, or after inflammation. In contrast, neither compound was effective in attenuating the intravesical plasma extravasation induced by turpentine. The data therefore suggest that the VVH and tissue inflammation responses are mediated via different mechanisms. In addition, the turpentine-induced VVH appears to be mediated, at least partially, by the B 2 receptor in the early phase, with the B 1 receptor only becoming important later.