title: Adenosine- and hypoxia-induced dilation of human coronary resistance arteries: evidence against the involvement of K(ATP) channels.
abstract: 1. 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. 2. 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. 3. The K(ATP) opener pinacidil (final conc. 5 x 10(-6) M) resulted in dilation, which was completely reversed by 5 x 10(-6) glibenclamide (84+/-14 vs -10+/-9%, pinacidil and pinacidil plus glibenclamide, respectively, P=0.009, n=5). 4. Adenosine (final conc. 10(-5) M) resulted in dilation, glibenclamide (5 x 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). 5. Hypoxia (8+/-3 mmHg O2) 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 x 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). 6. 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.
authors.affiliation: Division of Cardiovascular Medicine, Manchester Royal Infirmary, Oxford Road, Manchester, Greater Manchester.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Lynch
authors.forename: Clare
authors.initials: C
authors.lastname: Austin
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Izzard
mesh_terms: D000241:Adenosine / Q000494:pharmacology* / Q000502:physiology; D000368:Aged; D015687:Cell Hypoxia / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004108:Dilatation, Pathologic / Q000503:physiopathology*; D004347:Drug Interactions; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil; D000241:Adenosine; D005905:Glyburide