The purpose of this study was to examine atrial natriuretic peptide (ANP) secretion at rest and in response to moderate treadmill exercise (10 min, 4 km/h, 26% slope) in control dogs (n = 17) and in dogs (n = 14) with complete atrioventricular block produced by electrocauterization of the His bundle. Atrial rates were similar in both groups (103 +/- 13 vs. 102 +/- 9 beats/min at rest and 162 +/- 10 vs. 160 +/- 17 beats/min at exercise in control dogs and in dogs with atrioventricular block, respectively; mean +/- SE), but ventricular rate was markedly lower in dogs with atrioventricular block (47 +/- 9 and 61 +/- 10 beats/min at rest and exercise, respectively). The lower ventricular rate was associated with an increased cardiac preload, as evidenced by the higher right atrial pressure in dogs with atrioventricular block at rest (2.2 +/- 1.4 vs. 1.1 +/- 0.9 mmHg; p < 0.05) and exercise (7.6 +/- 3.1 vs. 4.2 +/- 1.7 mmHg; p < 0.05). Arterial plasma ANP concentrations were markedly higher at rest (151 +/- 21 vs. 36 +/- 10 pg/mL; p < 0.05) and exercise (353 +/- 31 vs. 72 +/- 17 pg/mL; p < 0.05) in dogs with atrioventricular block. This observation supports the hypothesis that atrial wall stretching is a major stimulus for ANP release at rest and exercise. Ventricular release of ANP could also contribute to the higher plasma ANP concentrations observed both at rest and during exercise in dogs with complete atrioventricular block. Indeed, a large ANP concentration gradient was measured between the aorta and the distal part of the coronary sinus in these dogs at rest (227 +/- 55 pg/mL) and exercise (240 +/- 57 pg/mL) but not in control dogs. Changes in heart rate and in vasopressin and catecholamine concentrations do not appear to play a major role in the control of ANP release; Finally, the higher arterial ANP concentrations in dogs with complete atrioventricular block do not modify the activity of the renin-angiotensin-aldosterone system at rest, nor its response to exercise.