Mechanism of atrial natriuretic peptide release with increased inspiratory resistance

Elevated plasma atrial natriuretic peptide (ANP) levels and concomitant increases in renal sodium and water excretion are often encountered in respiratory diseases associated with increased airway resistance such as obstructive sleep apnea. The present study utilized an anesthetized rat model to determine the principal mechanism(s) responsible for stimulation of ANP release in this clinical syndrome. A 10-minute increase in external resistive loading, which reduced peak tracheal pressure to -15 to -17 mm Hg produced a significant increase in both central venous pressure and fight atrial transmural pressure. This maneuver subsequently resulted in significant transient increases in glomerular filtration rate; urine flow; urinary Na⁺, K⁺, and Cl^- excretion; and urinary cyclic guanosine monophosphate (cGMP) excretion, which was taken as an index of increased circulating levels of ANP. Similar changes in renal function and cGMP excretion occurred when arterial PO₂ was lowered to a degree equivalent to that seen with increased resistive loading. Lowering arterial PO₂ also significantly increased mean central venous pressure and right atrial transmural pressure. Conversely, the resistive loading-induced changes in renal function and cGMP excretion did not occur when the reduction in arterial PO₂ was prevented by breathing a high O₂ gas mixture during the resistive loading. Additionally, O₂ supplementation prevented the increases in both mean central venous pressure and right atrial transmural pressure caused by Increased resistive loading. These data indicate that the elevated ANP release that results from an acute increase in external resistive loading is not caused by a decrease in intrathoracic pressure but rather suggest that the elevated ANP release is primarily caused by an increased fight atrial transmural pressure resulting from hypoxia-induced pulmonary vasoconstriction.