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Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat
Author(s) -
Buckingham Robin E.,
Hamilton Thomas C.,
Howlett David R.,
Mootoo Sheila,
Wilson Campbell
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11923.x
Subject(s) - cromakalim , glibenclamide , pharmacology , potassium channel , medicine , endocrinology , chemistry , anesthesia , diabetes mellitus
1 In rat isolated thoracic aortic rings pre‐contracted with noradrenaline (10 −6 m ), cromakalim (3 × 10 −7 ‐3 × 10 −5 m ) produced concentration‐related relaxation. This effect was progressively inhibited by increasing concentrations of the anti‐diabetic sulphonylurea drug, glibenclamide (10 −6 ‐10 −5 m ). 2 In rat isolated portal veins, cromakalim (3 × 10 −8 ‐10 −6 m ) produced concentration‐related inhibition of the spontaneous contractive activity and glibenclamide (3 × 10 −7 ‐3 × 10 −6 m ) prevented this inhibitory action in a concentration‐dependent manner. 3 In both rat aortic rings and portal veins, cromakalim (10 −5 m ) stimulated 86 Rb efflux. Prior exposure to glibenclamide (10 −7 ‐10 −6 m ) produced a concentration‐related inhibition of this response. 4 In conscious rats, cromakalim, 0.075 mg kg −1 i.v., produced a rapid and sustained fall in arterial blood pressure which was not influenced by pretreatment (2 h) with a large oral dose of glibenclamide (100 mg kg −1 ). 5 In conscious rats, the hypotensive action of cromakalim, 0.075 mg kg −1 i.v., was abolished by pretreatment (30 min) with glibenclamide, 20 mg kg −1 , given by the intravenous route. 6 The results suggest that the vasorelaxant and hypotensive actions of cromakalim involve a K + channel which can be inhibited by glibenclamide, but which may be distinct from the ATP‐sensitive K + channel of the pancreatic β‐cell.