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B 2 kinin receptors mediate the Indian red scorpion venom‐induced augmentation of visceral reflexes via the nitric oxide cyclic guanosine monophosphate pathway
Author(s) -
Kanoo S.,
Alex A. B.,
Tiwari A. K.,
Deshpande S. B.
Publication year - 2009
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2008.01953.x
Subject(s) - glibenclamide , kinin , cyclic guanosine monophosphate , nitric oxide , pharmacology , endocrinology , reflex , medicine , chemistry , phosphodiesterase inhibitor , receptor antagonist , nitric oxide synthase , anesthesia , receptor , antagonist , bradykinin , diabetes mellitus
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 ω ‐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 μg kg −1 ) evoked apnoea, bradycardia and hypotension lasting >60 s. Exposure to MBT venom (100 μg 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.