Atrial Natriuretic Peptide Improves Pulmonary Gas Exchange in Subjects Exposed to Hypoxia

Abstract

Atrial Natriuretic Peptide (ANP) is secreted in response to hypoxia and pulmonary vasoconstriction. The hormone modulates pulmonary vascular tone in vivo and decreases pulmonary edema in isolated lungs exposed to several toxic agents. In addition, ANP improves the barrier function of endothelial cell monolayers in vitro. The plasma levels of ANP are elevated in patients with high-altitude pulmonary edema. We hypothesized that under these circumstances, ANP improves pulmonary gas exchange by attenuating the transvascular permeation of plasma (water). Therefore, we studied the effect of low-dose ANP in 11 healthy mountaineers exposed to hypoxia in a single-blind, placebo-controlled, cross-over design. During four 1-h periods, the subjects were stepwise exposed to decreasing barometric pressure, with a minimum of 456 mm Hg (simulated altitude, 4,115 m). Infusion of 5 ng/kg/min human-ANP increased the plasma ANP concentrations approximately twofold. The plasma concentrations of cyclic GMP, which is the second messenger of ANP, rose approximately threefold. Infusion of ANP did not affect the hemodynamic or ventilatory response to hypoxia. The hemoglobin concentration, however, rose from 9.0 +/- 0.1 to 9.4 +/- 0.1 mmol/L (p < 0.01) during ANP infusion but not during placebo infusion. The change in plasma volume calculated from this hemoconcentration indicated that approximately 10% of the plasma volume had permeated into the interstitium. Despite the observed whole-body hemoconcentration, oxygen saturation was significantly higher during ANP infusion than during placebo infusion (84.7 +/- 1.7 versus 79.6 +/- 1.8%, p < 0.05), and the alveolar-arterial oxygen difference was significantly lower (3.5 +/- 0.7 versus 7.3 +/- 0.8 mm Hg, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)