Pharmacological characterization of rabbit corpus cavernosum relaxation mediated by the tissue kallikrein‐kinin system

Abstract

1 The roles of the tissue kallikrein-kinin system and nitric oxide (NO) release in Phoneutria nigriventer venom-induced relaxations of rabbit corpus cavernosum (RbCC) smooth muscle have been investigated by use of a bioassay cascade. 2 Phoneutria nigriventer venom (10–30 μg), porcine pancreatic kallikrein (100 mu), rabbit urinary kallikrein (10 mu), 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 μm) substantially potentiated Phoneutria nigriventer venom- and BK-induced RbCC relaxations without affecting those elicited by GTN. 3 The bradykinin B₂ receptor antagonist, Hoe 140 (d-Arg-[Hyp³, Thi⁵,d-Tic⁷, Oic⁸]-BK, 50 nm), aprotinin (10 μg ml⁻¹) and the tissue kallikrein inhibitor, Pro-Phe-Aph-Ser-Val-Gln-NH₂ (KIZD-06, 1.3 μm) significantly inhibited Phoneutria nigriventer venom-induced RbCC relaxations, without affecting those provoked by GTN and ACh. The B₁ receptor antagonist, [Leu⁹]des Arg¹⁰BK (0.5 μm) and soybean trypsin inhibitor (SBTI, 10 μg ml⁻¹) had no effect on Phoneutria nigriventer venom-induced RbCC relaxations. 4 The relaxations induced by Phoneutria nigriventer venom, porcine pancreas kallikrein, BK and ACh were significantly inhibited by N^ω-nitro-l-arginine methyl ester (l-NAME, 10 μm) but not by d-NAME (10 μm). l-NAME did not affect GTN-induced relaxations. l-Arginine (300 μm), but not d-arginine (300 μm), significantly reversed the inhibitory effect of l-NAME. 5 Our results indicate that Phoneutria nigriventer venom activates the tissue kallikrein-kininogen-kinin system in RbCC strips leading to NO release and suggest a functional role for this system in penile erection.