ATRIAL-NATRIURETIC-PEPTIDE IMPROVES PULMONARY GAS-EXCHANGE IN SUBJECTS EXPOSED TO HYPOXIA

Atrial Natriuretic Peptide (ANP) is secreted in response to hypoxia an d pulmonary vasoconstriction. The hormone modulates pulmonary vascular tons in vivo and decreases pulmonary edema in isolated lungs exposed to several toxic agents. In addition, ANP improves the barrier functio n of endothelial cell monolayers in vitro. The plasma levels of ANP ar e elevated in patients with high-altitude pulmonary edema. We hypothes ized that under these circumstances, ANP improves pulmonary gas exchan ge by attenuating the transvascular permeation of plasma (water). Ther efore, we studied the effect of low-dose ANP in 11 healthy mountaineer s exposed to hypoxia in a single-blind, placebo-controlled, cross-over design. During four 1-h periods, the subjects were stepwise exposed t o decreasing barometric pressure, with a minimum of 456 mm Hg (simulat ed altitude, 4,115 m). Infusion of 5 ng/kg/min human-ANP increased the plasma ANP concentrations approximately twofold. The plasma concentra tions of cyclic GMP, which is the second messenger of ANP, rose approx imately threefold. Infusion of ANP did not affect the hemodynamic or v entilatory 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 inf usion but not during placebo infusion. The change in plasma volume cal culated from this hemoconcentration indicated that approximately 10% o f the plasma volume had permeated into the interstitium. Despite the o bserved whole-body hemoconcentration, oxygen saturation was significan tly 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). The increase in arterial oxygen saturation was inversel y correlated with the alveolar-arterial oxygen difference (r = 0.66, p < 0.05), which is compatible with the hypothesis that oxygen saturati on increased as a result of an improved pulmonary gas exchange.