Low-dose endothelin-1 potentiates volume-induced secretion of atrial natriuretic factor

To evaluate the role of calcium in volume-induced secretion of atrial natriuretic factor (ANF), effects of verapamil and endothelin-1 (ET-1), both known to influence free intracellular calcium, were studied during saline infusion in seven conscious instrumented dogs. Fifteen minutes after intravenous injection of placebo or verapamil (0.25 mg/kg) or during continuous ET-1 infusion (at 5 ng.kg-1.min-1), saline (10% body wt) was infused during 40 min. Saline produced a rise (P less than 0.001) of plasma ANF from 28.1 +/- 6.3 to 50.4 +/- 12.9 pM after placebo, from 30.2 +/- 6.1 to 51.1 +/- 8.5 pM after verapamil, and from 31.2 +/- 6.1 to 81.0 +/- 12.9 pM with ET-1. This increase was comparable after placebo and verapamil, but was 80% greater with ET-1 (P less than 0.02). Plasma ET-1, unchanged after placebo, rose (P less than 0.001) from 1.7 +/- 0.5 to 38.3 +/- 9.2 pM with ET-1. In the three experiments, heart rate and left atrial pressure (LAP) increased (P less than 0.001) similarly. The linear relation between ANF and LAP was steeper with ET-1 than with saline or verapamil (both P less than 0.05), indicating that the enhanced ANF secretion with ET-1 was occurring at all levels of LAP. Thus volume-induced secretion of ANF is not suppressed by verapamil, but is directly enhanced by low-dose ET-1, known to activate the phosphoinositide pathway.