Neural control of ANF release in hypoxia and pulmonary hypertension

Abstract

Hypoxia causes the release of atrial natriuretic factor (ANF), but the mechanisms are not yet understood. This study examined the relative contribution of pulmonary arterial hypertension, neural pathways, increased heart rate, or increased atrial size to the ANF response. Alveolar hypoxia [fractional concentration of O2 in inspired gas (FIo2) = 0.1] or pulmonary arterial hypertension (25-45 mmHg) was induced for 10 min in four series (n = 4-12 each) of anesthetized, mechanically ventilated pigs. During hypoxia, plasma ANF concentrations increased by 129 +/- 52 (SE) pg/ml (or 271 +/- 105%) over baseline (35 +/- 7 pg/ml; P less than 0.01) (series 1). There was also a significant increase of pulmonary arterial pressure, heart rate, central venous pressure, and pulmonary capillary wedge pressure. Repeated pulmonary hypertension induced by intravenous air infusion caused a repeated and reversible 125 +/- 14% increase (P less than 0.001) of plasma ANF, and this response was totally abolished by lesion of the cervical vagosympathetic trunks (series 2). Lesion of these nerves 1 h before hypoxia also decreased the ANF response to hypoxia by 45-58% (P less than 0.01), whereas responses of heart rate and atrial pressures were unchanged (series 3). The ANF response to hypoxia, expressed in percent of baseline, was not affected by 0.2 mg/kg propranolol (PR) (no PR: 145 +/- 63%; PR: 151 +/- 82%; not significantly different from series 1 and control, series 3), although the increase in heart rate (no PR: 61 +/- 15 beats/min) was almost abolished (PR: 17 +/- 5 beats/min) (series 4). Hypoxia caused no significant changes in right and left atrial peak volume regardless of propranolol, as measured with an electrical conductance catheter. The results indicate that a new neural reflex of probably pulmonary arterial origin mediates approximately 50% of the ANF response to hypoxia. The remaining ANF response remains to be explored further and cannot be explained by conventional release mechanisms such as atrial stretch and pulsatility alone.