SYNERGISTIC REGULATION OF ANF IN ISOLATED RAT HEARTS

The interaction between cardiac sympathetic stimulation of atrial natr iuretic factors (ANF) release and left atrial stretch was examined in groups (n = 5 or 6) of isolated, perfused (10 ml/min), paced rat heart s. Left atrial stretch, produced by an increase in atrial pressure of 1.1 +/- 0.2 mmHg over 8 min, transiently (4 min) increased ANF release by 46 +/- 4% over baseline (220 pg/ml buffer; P < 0.05). Infusion of 1 mu M norepinephrine (NE) over 28 min caused a sustained increase in ANF release of 76 +/- 10% (P < 0.05). Atrial stretch plus NE caused ad ditive effects on ANF release during stretch but 2.4 times the additiv e effects after stretch (P < 0.05). To examine whether resting tension modulates the ANF response to sympathetic stimulation, the left atriu m was stretched throughout the experiment by increasing the atrial pre ssure by 1-1.5 mmHg. Infusion of 1 mu M NE over 28 min increased ANF r elease by 216 +/- 46% (P < 0.01) in the prestretched heart, compared w ith a calculated summed increase of 85% due to NE alone plus prestretc h alone. Infusion of 0.5 mu M veratridine, known to stimulate ANF via mechanical effects on the heart, increased ANF release by 88 +/- 3% (P < 0.01). Scorpion venom, known to dose dependently stimulate ANF secr etion via activation of neuronal sodium channels, elicits a negligible increase in ANF release at the threshold concentration of 0.1 mu M. T he combined infusion of 0.5 mu M veratridine plus 0.1 mu M venom incre ased ANF release by 239 +/- 53% (n = 6, P < 0.01). The ANF responses w ere not correlated with the increase in left atrial pressure, perfusio n pressure, or left ventricular developed pressure; thus cardiac mecha nics could not explain the dramatically augmented ANF release. The res ults indicate that stretch of the left atrium has transient and modest effects on ANF release in the isolated heart but greatly potentiates the ANF response to cardiac sympathetic activation.