Alveolar hypoxia is a powerful stimulus for ANF release in conscious lambs.

The effect of acute alveolar hypoxia [fractional concentration of O2 in inspired gas (FIo2) = 0.1] for 10 min [arterial PO2 = 37 +/- 4 (SE) mmHg] and of blood volume expansion (7 and 15% of calculated blood volume) on atrial natriuretic factor (ANF) release was examined in groups of awake, instrumented young lambs. Systemic venous plasma ANF concentrations increased 1.6-fold (P less than 0.01) during blood volume expansion of 7%, 1.9-fold (P less than 0.01) during acute hypoxia, and 2.2-fold (P less than 0.005) during blood volume expansion of 15%. In lambs with prior 15% blood volume expansion, alveolar hypoxia further increased ANF concentrations 3.1-fold (P less than 0.01), suggesting synergism between volume and hypoxia stimuli. Hypoxia-induced ANF release correlated best with increased pulmonary arterial pressure, a potential mediator of the ANF response (r = 0.67; P less than 0.016). Increased differences between pulmonary arterial and systemic venous plasma ANF concentrations (from 11 to 134 pg/ml) indicate that hypoxia causes increased release of ANF from the heart rather than decreased metabolism of circulating ANF. Pulmonary arterial plasma ANF during hypervolemic hypoxia had immunological and chromatographic (high-performance liquid chromatography) properties of Pro-ANF-(99-126) [alpha-ANF-(1-28)]. Thus alveolar hypoxia (FIo2 = 0.1) is as potent as 15% blood volume expansion in increasing the concentration of circulating ANF. This newly described endocrine response could be important during alveolar hypoxia to decrease pulmonary vasoconstriction and fluid accumulation in the lung.