ATP-SENSITIVE POTASSIUM CHANNELS REGULATE STIMULATED ANF SECRETION INISOLATED RAT-HEART

Perfused hearts (n = 127) were exposed to acute hypoxia (10% O-2 for 1 2 or 20 min) or left atrial stretch (increase in atrial pressure) in t he presence or absence of 100 mu mol/l ATP-sensitive potassium channel blocker (tolbutamide) or openers (pinacidil and diazoxide). Hypoxia a lone elicited a prolonged atrial natriuretic factor (ANF) release, pea king at 74% over baseline (P < 0.01); with tolbutamide, ANF secretion peaked at 132% over baseline (P < 0.01). Pinacidil and diazoxide aboli shed the ANF response to hypoxia (P < 0.01). Atrial stretch alone (1 m mHg) transiently (2 min) increased ANF by 56% (P < 0.05); with tolbuta mide, ANF increased transiently by 124% and showed a prolonged increas e of 52% (P < 0.05). With tolbutamide, graded stretch (0.5-2.3 mmHg) i nduced 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 mmRg, a nd 14% at 2.22 mmHg] and a saturating prolonged ANF response. Tolbutam ide increased the ANF response nonsignificantly at lower doses (30 mu mol/l) and had no effect at 1 mu mol/l. Pinacidil abolished the stretc h-induced ANF release. These results suggest that ATP-sensitive potass ium channels are extremely potent modulators of stimulated ANF secreti on.