Mechanisms underlying the augmentation of phenylbiguanide and capsaicin induced cardiorespiratory reflexes by Mesobuthus tamulus venom

Phenylbiguanide (PBG) and capsaicin evoke cardiorespiratory reflexes utilizing two separate pathways. It is known that Indian Red Scorpion (Mesobuthus tumulus; MBT) venom augments PBG (5-HT(3)) responses but, the effect of MBT venom on capsaicin (TRPV1)-induced response is not known. Therefore, the present study was undertaken to ascertain whether MBT venom also augments the capsaicin-induced reflex responses involving mechanisms similar to PBG. Experiments were performed on anaesthetized adult rats. Blood pressure, respiratory excursions and ECG were recorded. At the end of each experiment pulmonary water content was determined. PBG (10 μg/kg) produced hypotension, bradycardia and apnoea-bradypnoea. Capsaicin (10 μg/kg) also produced hypotension, bradycardia and apnoea-bradypnoea. MBT venom (100 μg/kg) augmented PBG as well as capsaicin-induced responses and produced pulmonary oedema (increased pulmonary water content). Prostaglandin synthase inhibitor (indomethacin; 10 mg/kg) blocked the venom-induced augmentation of PBG and capsaicin reflexes. Kinin synthase inhibitor (aprotinin; 6000 KIU) and guanylate cyclase (GC) inhibitor (methylene blue; 5 mg/kg) blocked the venom-induced augmentation of PBG response but not the capsaicin response. However, pulmonary oedema was blocked by these antagonists. Phosphodiesterase V inhibitor (sildenafil; 100 μg/kg) augmented the PBG response but not the capsaicin response, though pulmonary oedema was seen in both the groups. The present results indicate that MBT venom also augments the capsaicin-induced responses. The augmentation of capsaicin response involves PGs and pulmonary oedema-independent mechanisms whereas, the augmentation of PBG response involves kinin mediated GC-cGMP pathway and pulmonary oedema-dependent mechanisms.