Pharmacological characterization of RMP-7, a novel bradykinin agonist in smooth muscle

Abstract

RMP-7 is a bradykinin (BK) agonist designed to be resistant to kininases such as angiotensin-converting enzyme (ACE). Pharmacological assays were performed with RMP-7 in isolated guinea-pig ileum and rat mesenteric artery. RMP-7 induced contractile responses in the guinea-pig ileum, where the apparent affinity of the peptide (pD(2)) was significantly lower than that determined for BK (7.3 +/- 0.07 vs. 8.3 +/- 0.05, respectively). HOE-140 blocked this effect indicating that B-2 receptor was involved. Captopril (1 mu M) had no potentiating effect on RMP-7 but increased pD(2) value determined for BK (8.8 +/- 0.1), confirming a high resistance of RMP-7 to the ACE. in rat mesenteric artery, RMP-7 induced endothelium-dependent relaxation (7.8 +/- 0.4), with a higher affinity than that of BK which induced vasodilatation only in the presence of 1 mu M captopril (6.9 +/- 0.36). Nevertheless, the maximum effect induced by RMP-7 was lower than that of BK in contrast to that observed in guinea-pig ileum although B-2 receptor was involved in both cases. We concluded that: RMP-7 is greatly resistant to the ACE and that the receptor sites activated by RMP-7 and BK show important differences in vascular and non-vascular preparations probably due to the different sensitivity of the B-2 receptor to RMP-7. (C) 1999 Elsevier Science B.V. All rights reserved.