Cardiac atria are the primary source of ANP release in hypoxia-adapted rats.

AIMS: atrial natriuretic peptide (ANP) is released from the heart in response to hypoxia and helps mitigate the development of pulmonary hypertension. However, the mechanism of hypoxia-induced ANP release is not clear. The cardiac atria are the primary source of ANP secretion under normal conditions, but right ventricular ANP expression is markedly up-regulated during adaptation to hypoxia. We sought to better understand mechanisms of cardiac ANP release during adaptation to hypoxia. MAIN METHODS: we measured hypoxia-induced ANP release from isolated perfused rat hearts obtained from normoxia and hypoxia-adapted rats before and after removal of the atria. KEY FINDINGS: in both normoxia- and hypoxia-adapted hearts, ANP levels in the perfusate increased within 15 min of hypoxia. Hypoxia-induced ANP release was greater from hypoxia-adapted than normoxia-adapted hearts. Baseline and hypoxia-induced ANP release were considerably greater with the atria intact (213±29 to 454±62 and 281±26 to 618±87 pg/ml for normoxia- and hypoxia-adapted hearts respectively, P<0.001 for both) than with atria removed (94±17 to 131±32 and 103±26 to 201±55 pg/ml, respectively, P<0.002 for both). Hypoxia-induced ANP release was reduced over 80% by removing the atria in both normoxia- and in hypoxia-adapted hearts. Acute hypoxia caused a transient increase in lactate release and reductions in pH and left ventricular generated force, but no differences in pH or left ventricular generated force were seen between normoxia- and hypoxia-adapted rats. SIGNIFICANCE: we conclude that the right ventricle is not a major source of cardiac ANP release in normoxia- or hypoxia-adapted rats.