Sulfonylurea receptor ligands modulate stretch-induced ANF secretion in rat atrial myocyte culture

Stretch-induced atrial natriuretic factor (ANF) secretion was studied in cu ltures of neonate atrial appendage myocytes. Stretch, applied for 40 min by hypotonic swelling, increased the mean area of 44 individually imaged myoc ytes by 4.8-8.8% (P < 0.0001) at 6 min and by 2.3-6.2% (P < 0.05) at 35 min . Stretch increased immunoreactive ANF release by 42% (P< 0.05) from a base line of 315 pg/ml. The ATP-sensitive K+ (K-ATP)-channel blocker tolbutamide (100 mu mol/l) increased the stretch-stimulated release to 84% (P< 0.01) o ver baseline, whereas lower concentrations (1, 10, and 30 mu mol/l) had no stimulatory effect. The K-ATP-channel opener diazoxide (0.1, 1, 10, 30, and 100 mu mol/l) inhibited stretch-plus tolbutamide-stimulated ANF release in a concentration-dependent manner, with IC50 = 2.2 mu mol/l, although 100 m u mol/l diazoxide did not reduce the increase in mean cell area. The stretc h-stimulated K-ATP current, monitored in 82 whole cell recordings with sulf onylurea receptor (SUR) ligands, was inversely correlated with the stretch- induced ANF release (r(2) = 0.79, P<0.0001). In the absence of stretch, the K-ATP current had no relationship with baseline ANF release, and baseline ANF release was not affected by the K-ATP-channel modulators. The results s how that SUR ligands that open K-ATP channels inhibit stretch-induced ANF r elease in atrial myocytes, in correlation with the stretch-activated K-ATP current. The subcellular site of action of the SUR ligands-plasmalemma or i ntracellular organelles-remains to be determined.