The separate effects of hypoxia and ischemia on atrial natriuretic peptide (ANP) release were evaluated in Langendorff-perfused rabbit hearts. Heart rate, coronary flow, and atrial and ventricular volumes were kept constant. Hypoxia was induced for 20 min at room temperature in seven hearts and at 37 degrees C in a second group of seven hearts. A third group of eight hearts was subjected to global ischemia for 20 min by reducing coronary flow to 1 ml/min at room temperature. All hearts were reoxygenated/reperfused at 37 degrees C for 30 min. Hypoxia at 37 degrees C induced a significant increase in ANP release. In contrast, both room temperature hypoxia and ischemia were characterized by a significant decrease in ANP release, despite hemodynamic alterations similar to those recorded during hypoxia at 37 degrees C. Both reoxygenation and reperfusion induced a prompt reversal of the changes of ANP release observed during the period of oxygen deprivation. These data demonstrate that decreased oxygen availability and reduced coronary flow are not the primary factors affecting release of ANP during ischemia and that alterations of myocardial temperature may play a major role in this phenomenon.