Synergistic regulation of ANF in isolated rat hearts

The interaction between cardiac sympathetic stimulation of atrial natriuretic factors (ANF) release and left atrial stretch was examined in groups (n = 5 or 6) of isolated, perfused (10 ml/min), paced rat hearts. 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 microM norepinephrine (NE) over 28 min caused a sustained increase in ANF release of 76 +/- 10% (P < 0.05). Atrial stretch plus NE caused additive effects on ANF release during stretch but 2.4 times the additive effects after stretch (P < 0.05). To examine whether resting tension modulates the ANF response to sympathetic stimulation, the left atrium was stretched throughout the experiment by increasing the atrial pressure by 1-1.5 mmHg. Infusion of 1 microM NE over 28 min increased ANF release by 216 +/- 46% (P < 0.01) in the prestretched heart, compared with a calculated summed increase of 85% due to NE alone plus prestretch alone. Infusion of 0.5 microM 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 secretion via activation of neuronal sodium channels, elicits a negligible increase in ANF release at the threshold concentration of 0.1 microM. The combined infusion of 0.5 microM veratridine plus 0.1 microM venom increased ANF release by 239 +/- 53% (n = 6, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)