B2 kinin receptors mediate the Indian red scorpion venom-induced augmentation of visceral reflexes via the nitric oxide cyclic guanosine monophosphate pathway

Aim: This study was performed to delineate the kinin (receptor)-dependent pathways in the Indian red scorpion (Mesobuthus tamulus; MBT) venom-induced pulmonary oedema as well as the augmentation of cardio-pulmonary reflexes evoked by phenyldiguanide (PDG). Methods: In urethane-anaesthetized adult rats, the effect of venom on the PDG reflex responses (blood pressure, heart rate and respiration rate) and the pulmonary water content was ascertained using various antagonists (des-Arg, B-1 receptor antagonist; Hoe 140, B-2 receptor antagonist; N-omega-nitro-L-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor; methylene blue, soluble guanylate cyclase inhibitor; and glibenclamide, K-ATP(+) channel blocker). The effect of phosphodiesterase V inhibitor (sildenafil citrate) on the reflex response and the pulmonary water content was also examined and compared with venom-induced responses. Results: Intravenous injection of PDG (10 mu g kg(-1)) evoked apnoea, bradycardia and hypotension lasting > 60 s. Exposure to MBT venom (100 mu g kg(-1)) for 30 min augmented the PDG reflex responses by two times and increased the pulmonary water content, significantly. Hoe 140 blocked the venom-induced responses (augmentation of PDG reflex and increased pulmonary water content) whereas des-Arg did not. L-NAME, methylene blue or glibenclamide also blocked the venom-induced responses. Furthermore, sildenafil citrate (that increases cGMP levels) produced augmentation of PDG reflex response and increased the pulmonary water content as seen with venom. Conclusion: The results indicate that venom-induced responses involve B-2 kinin receptors via the NO-dependent guanylate cyclase-cGMP pathway involving K-ATP(+) channels.