Jaggar S I, Habib S, Rice A S
Department of Anaesthetics, Imperial College School of Medicine, St. Mary's Hospital, London, UK.
Pain. 1998 Apr;75(2-3):169-76. doi: 10.1016/s0304-3959(97)00217-0.
This study assessed the relative involvement of the two bradykinin (Bk) receptors (B1 and B2) 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-Arg9[Leu8]-Bk (B1) and HOE 140 (B2) were tested both in prophylactic (pre-inflammation administration) and therapeutic (post-inflammation administration) scenarios. Compared with control animals, des-Arg9[Leu8]-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 B2 receptor in the early phase, with the B1 receptor only becoming important later.
本研究评估了两种缓激肽（Bk）受体（B1和B2）在膀胱炎动物模型中观察到的内脏-内脏超反射（VVH）和血浆外渗中的相对参与情况。在预防性（炎症前给药）和治疗性（炎症后给药）两种情况下，测试了竞争性受体拮抗剂去-Arg9[Leu8]-Bk（B1）和HOE 140（B2）的作用。与对照动物相比，去-Arg9[Leu8]-Bk对膀胱对炎症的超反射反应没有影响，除非在炎症后5小时给药。然而，HOE 140在1 mg/kg、2 mg/kg和7.5 mg/kg剂量下能够减轻炎症诱导的内脏-内脏超反射（VVH）。无论药物在炎症前还是炎症后给药，这种作用都很明显。相比之下，这两种化合物都不能有效减轻松节油诱导的膀胱内血浆外渗。因此，数据表明VVH和组织炎症反应是通过不同机制介导的。此外，松节油诱导的VVH在早期似乎至少部分由B2受体介导，而B1受体仅在后期变得重要。
