Rgj. Westendorp et al., ATRIAL-NATRIURETIC-PEPTIDE IMPROVES PULMONARY GAS-EXCHANGE IN SUBJECTS EXPOSED TO HYPOXIA, The American review of respiratory disease, 148(2), 1993, pp. 304-309
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.