title: A Pharmacological Examination of the Cardiovascular Effects of Malayan Krait (Bungarus candidus) Venoms.
abstract: Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension) are often clinical outcomes of snake envenoming. Malayan krait (Bungarus candidus) envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated thein vivoandin vitrocardiovascular effects ofB. candidusvenoms from Southern (BC-S) and Northeastern (BC-NE) Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms.B. candidusvenoms (50 µg/kg-100 µg/kg, i.v.) caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I) followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II) prior to a small decrease in blood pressure (phase III). Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.). The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v.) or atropine (5 mg/kg, i.v.). BC-S and BC-NE venoms (0.1 µg/kg-100 µg/ml) induced concentration-dependent relaxation (EC50= 8 ± 1 and 13 ± 3 µg/mL, respectively) in endothelium-intact aorta. The concentration-response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM), or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO) is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused byB. candidusvenoms may be due to a combination of vascular mediators (i.e., NO) and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors.
authors.affiliation: Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand. janchai1@pmk.ac.th.
authors.forename: Janeyuth
authors.initials: J
authors.lastname: Chaisakul
authors.affiliation: Department of Physiology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand. hatthachoteting@gmail.com.
authors.forename: Muhamad Rusdi Ahmad
authors.initials: MR
authors.lastname: Rusmili
authors.affiliation: Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand. janchai1@pmk.ac.th.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hodgson
authors.affiliation: Queen Saovabha Memorial Institute, The Thai Red Cross Society, Bangkok 10330, Thailand. kijja_suwan@yahoo.com.
authors.forename: Panadda
authors.initials: P
authors.lastname: Hatthachote
authors.affiliation: Queen Saovabha Memorial Institute, The Thai Red Cross Society, Bangkok 10330, Thailand. anjaree.in@gmail.com.
authors.forename: Kijja
authors.initials: K
authors.lastname: Suwan
authors.affiliation: Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand. krongkarnc@gmail.com.
authors.forename: Anjaree
authors.initials: A
authors.lastname: Inchan
authors.affiliation: Queen Saovabha Memorial Institute, The Thai Red Cross Society, Bangkok 10330, Thailand. lchanhome@yahoo.com.
authors.forename: Lawan
authors.initials: L
authors.lastname: Chanhome
authors.affiliation: Jeffrey Cheah School of Medicine and Health Sciences, Monash University Sunway Campus, Bandar Sunway 46150, Malaysia. iekhsan.othman@monash.edu.
authors.forename: Iekhsan
authors.initials: I
authors.lastname: Othman
authors.affiliation: Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand. krongkarnc@gmail.com.
authors.forename: Krongkarn
authors.initials: K
authors.lastname: Chootip
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D017838:Bungarus; D004546:Elapid Venoms / Q000633:toxicity*; D018738:Hexamethonium / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D004546:Elapid Venoms; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D009569:Nitric Oxide; D018738:Hexamethonium; D001285:Atropine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
keywords: Malayan krait; cardiovascular; hypotension; rat; venom