Amiloride blocks the inhibition of fetal lung liquid secretion caused by AVP but not by asphyxia.
We have examined whether the activation of Na+ channels, located on the luminal surface of pulmonary epithelial cells, mediates the inhibitory effects of both arginine vasopressin (AVP) and moderate asphyxia on fetal lung liquid secretion. Lung liquid secretion rates were measured in chronically catheterized fetal sheep during AVP infusions and during periods of asphyxia with and without an Na+ transport blocker (amiloride; 10(-4) M) present in lung liquid. Lung liquid secretion rates were also measured during epinephrine infusions with amiloride present in lung liquid. These secretion rates were compared with measurements made during a preceding control period. Both asphyxia and an infusion of AVP significantly reduced the rate of secretion of fetal lung liquid from 8.4 +/- 1.5 and 18.0 +/- 3.7 to 3.6 +/- 1.0 (P < 0.01) and 5.5 +/- 2.1 ml/h (P < 0.01), respectively. The addition of amiloride to lung liquid did not reverse the inhibitory effects of asphyxia on lung liquid secretion (8.6 +/- 0.8 vs. 0.7 +/- 0.4 ml/h) but did block the inhibitory effects of both epinephrine (14.8 +/- 4.4 vs. 13.8 +/- 3.1 ml/h) and AVP (18.0 +/- 3.7 vs. 19.5 +/- 5.0 ml/h). The addition of amiloride to lung liquid during fetal normoxia did not significantly affect fetal lung liquid secretion rates (8.2 +/- 1.1 vs. 7.4 +/- 0.7 ml/h). We conclude that the inhibitory effect of AVP on fetal lung liquid secretion, like that of epinephrine, involves the activation of luminal surface Na+ channels, whereas the inhibitory effect of asphyxia does not.
Department of Physiology, Monash University, Clayton, Victoria, Australia.
S B
SB
Hooper
M J
MJ
Wallace
R
R
Harding
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001237:Asphyxia / Q000503:physiopathology*; D001784:Blood Gas Analysis; D001834:Body Water / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000502:physiology*; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy; D012756:Sheep; D015222:Sodium Channels / Q000187:drug effects
D006454:Hemoglobins; D015222:Sodium Channels; D001127:Arginine Vasopressin; D000584:Amiloride; D004837:Epinephrine