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Adenosine‐ and hypoxia‐induced dilation of human coronary resistance arteries: evidence against the involvement of K ATP channels
Author(s) -
Lynch Fiona M,
Austin Clare,
Heagerty Anthony M,
Izzard Ashley S
Publication year - 2006
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 - 10.1038/sj.bjp.0706622
Subject(s) - glibenclamide , pinacidil , adenosine , hypoxia (environmental) , medicine , cardiology , endocrinology , coronary circulation , vascular resistance , anesthesia , chemistry , blood pressure , oxygen , blood flow , diabetes mellitus , organic chemistry
The ATP‐sensitive potassium (K ATP ) channel may be an important mediator of metabolic dilation in the human coronary circulation. As adenosine and hypoxia are considered to be major mediators of metabolic dilation in the coronary circulation, we investigated the effect of glibenclamide (a K ATP channel blocker) on adenosine and hypoxic dilation of human coronary resistance arteries, with myogenic tone, in vitro . Vessels were dissected from the atrial appendage from consenting patients and studied in vitro using a pressure arteriograph system. Segments of coronary resistance artery were pressurized to 60 mmHg and the vessels studied developed spontaneous myogenic tone. The K ATP opener pinacidil (final conc. 5 × 10 −6 M ) resulted in dilation, which was completely reversed by 5 × 10 −6 glibenclamide (84±14 vs −10±9%, pinacidil and pinacidil plus glibenclamide, respectively, P =0.009, n =5). Adenosine (final conc. 10 −5 M ) resulted in dilation, glibenclamide (5 × 10 −6 and 10 −5 M ) was without effect (118±12 vs 104±16% adenosine and adenosine plus 10 −5 glibenclamide, respectively, n.s., n =4). Hypoxia (8±3 mmHg O 2 ) resulted in a dilation that reversed when normoxic conditions were restored (60±9 vs 3±11% hypoxia and post‐hypoxia, respectively, P =0.014, n =3). The hypoxic dilation was not affected by glibenclamide (63±14 vs 55±6% hypoxia and hypoxia plus glibenclamide, respectively, n.s., n =4). In a further series of experiments, vessels were incubated with glibenclamide (5 × 10 −6 ) prior to a hypoxic challenge; again, glibenclamide was without effect on the hypoxic dilation (−0.008±2 vs 95±3% glibenclamide and glibenclamide plus hypoxia, respectively, P =0.0005, n =3). These data demonstrate that glibenclamide is without effect on both adenosine and hypoxic dilation of human coronary resistance arteries with myogenic tone, from the right atrial appendage in vitro . Our findings suggest that the K ATP channel is unlikely to be a major mediator of metabolic dilation in these arteries.British Journal of Pharmacology (2006) 147 , 455–458. doi: 10.1038/sj.bjp.0706622