PHARMACOLOGICAL CHARACTERIZATION OF RABBIT CORPUS CAVERNOSUM RELAXATION MEDIATED BY THE TISSUE KALLIKREIN-KININ SYSTEM

1 The roles of the tissue kallikrein-kinin system and nitric oxide (NO ) release in Phoneutria nigriventer venom-induced relaxations of rabbi t corpus cavernosum (RbCC) smooth muscle have been investigated by use of a bioassay cascade. 2 Phoneutria nigriventer venom (10-30 mu g), p orcine pancreatic kallikrein (100 mu), rabbit urinary kallikrein (10 m u), bradykinin (BK, 0.3-3 nmol), acetylcholine (ACh, 0.3-30 nmol) and glyceryl trinitrate (GTN, 0.5-10 nmol) caused relaxations of the RbCC strips. Captopril (1 mu M) substantially potentiated Phoneutria nigriv enter venom- and BK-induced RbCC relaxations without affecting those e licited by GTN. 3 The bradykinin B-2 receptor antagonist, Hoe 140 (D-A rg-[Hyp(3),Thi(5), D-Tic(7),Oic(8)]-BK, 50 nM), aprotinin (10 mu g ml( -1)) and the tissue kallikrein inhibitor, Pro-Phe-Aph-Ser-Val-Gln-NH2 (KIZD-06, 1.3 mu M) significantly inhibited Phoneutria nigriventer ven om-induced RbCC relaxations, without affecting those provoked by GTN a nd ACh. The B-1 receptor antagonist, [Leu(9)]des Arg(10)BK (0.5 mu M) and soybean trypsin inhibitor (SBTI, 10 mu g ml(-1)) had no effect on Phoneutria nigriventer venom-induced RbCC relaxations. 4 The relaxatio ns induced by Phoneutria nigriventer venom, porcine pancreas kallikrei n, BK and ACh were significantly inhibited by N-omega-nitro-L-arginine methyl ester (L-NAME, 10 mu M) but not by D-NAME (10 mu M). L-NAME di d not affect GTN-induced relaxations. L-Arginine (300 mu M), but not D -arginine (300 mu M), significantly reversed the inhibitory effect of L-NAME. 5 Our results indicate that Phoneutria nigriventer venom activ ates the tissue kallikrein-kininogen-kinin system in RbCC strips leadi ng to NO release and suggest a functional role for this system in peni le erection.