ATP-sensitive potassium channels regulate stimulated ANF secretion in isolated rat heart.
Perfused hearts (n = 127) were exposed to acute hypoxia (10% O2 for 12 or 20 min) or left atrial stretch (increase in atrial pressure) in the presence or absence of 100 mumol/l ATP-sensitive potassium channel blocker (tolbutamide) or openers (pinacidil and diazoxide). Hypoxia alone elicited a prolonged atrial natriuretic factor (ANF) release, peaking at 74% over baseline (P < 0.01); with tolbutamide, ANF secretion peaked at 132% over baseline (P < 0.01). Pinacidil and diazoxide abolished the ANF response to hypoxia (P < 0.01). Atrial stretch alone (1 mmHg) transiently (2 min) increased ANF by 56% (P < 0.05); with tolbutamide, ANF increased transiently by 124% and showed a prolonged increase of 52% (P < 0.05). With tolbutamide, graded stretch (0.5-2.3 mmHg) induced a bell-shaped transient (2-min) increase of ANF release [-3% at 0.5 mmHg, 124% (P < 0.05) at 1.0 mmHg, 80% (P < 0.05) at 1.48 mmHg, and 14% at 2.22 mmHg] and a saturating prolonged ANF response. Tolbutamide increased the ANF response nonsignificantly at lower doses (30 mumol/l) and had no effect at 1 mumol/l. Pinacidil abolished the stretch-induced ANF release. These results suggest that ATP-sensitive potassium channels are extremely potent modulators of stimulated ANF secretion.
Xu
T
T
Department of Molecular Physiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Jiao
J H
JH
Pence
R A
RA
Baertschi
A J
AJ
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D016279:Atrial Function, Left; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010812:Physical Stimulation; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology
D015221:Potassium Channels; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D014044:Tolbutamide