sildenafil-citrate and icatibant

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).. 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.. Intravenous injection of PDG (10 microg kg(-1)) evoked apnoea, bradycardia and hypotension lasting >60 s. Exposure to MBT venom (100 microg 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.. The results indicate that venom-induced responses involve B(2) kinin receptors via the NO-dependent guanylate cyclase-cGMP pathway involving K(+)(ATP) channels.

Topics: Adrenergic beta-Antagonists; Animals; Biguanides; Bradykinin; Bradykinin B2 Receptor Antagonists; Enzyme Inhibitors; Glyburide; Guanosine Monophosphate; Heart; Hypoglycemic Agents; Lung; Male; Metabolic Networks and Pathways; Methylene Blue; NG-Nitroarginine Methyl Ester; Nitric Oxide; Piperazines; Pulmonary Edema; Purines; Rats; Receptor, Bradykinin B2; Reflex; Scorpion Venoms; Scorpions; Serotonin Receptor Agonists; Sildenafil Citrate; Sulfones