N Choo1, A L Liu, A M Perks. 1. Departments of Obstetrics and Gynecology and Zoology, University of British Columbia, Vancouver, BC, Canada V6H 3V5.
Abstract
BACKGROUND: Lung liquid reabsorption in newborns with respiratory distress syndrome can be deficient. Respiratory distress syndrome is often seen in infants of diabetic mothers, in whom the neonatal surge of glucagon is suppressed. AIM: To investigate the possible effects of glucagon on lung liquid reabsorption. METHODS: Lungs from near term fetal guinea pigs (62 (2) days gestation; term = 67 days) were supported in vitro for three hours; lung liquid production and reabsorption were monitored by a dye dilution method. RESULTS: Untreated control preparations produced fluid at 1.75 (0.33) ml/h per kg body weight, and did not change significantly in three hours; those immersed in 10(-12) M glucagon during the middle hour showed no significant change, but those given higher concentrations all showed significant reductions in fluid production or even reabsorption (65.6 (10.3)% fall at 10(-11) M, 70.0 (6.3)% fall at 10(-10) M, and 90.6 (11.1)% fall at 10(-9) M; based on 54 preparations). At 10(-9) M glucagon, 12 out of 30 preparations reabsorbed fluid. The linear log dose-response curve (r(2) = 0.94) gave a theoretical threshold at 4 x 10(-15) M glucagon. Responses appeared to involve the amiloride sensitive Na(+) based reabsorptive system: responses to 10(-9) M glucagon appeared to be reduced by 10(-6) M amiloride, and were abolished by 10(-5) M amiloride (based on 72 preparations). CONCLUSIONS: The results suggest that the surge of glucagon at birth may help to drain the lungs of fluid. As glucagon liberates cAMP, which also stimulates surfactant, glucagon is worth consideration for possible use in neonatal respiratory distress.
BACKGROUND: Lung liquid reabsorption in newborns with respiratory distress syndrome can be deficient. Respiratory distress syndrome is often seen in infants of diabetic mothers, in whom the neonatal surge of glucagon is suppressed. AIM: To investigate the possible effects of glucagon on lung liquid reabsorption. METHODS: Lungs from near term fetal guinea pigs (62 (2) days gestation; term = 67 days) were supported in vitro for three hours; lung liquid production and reabsorption were monitored by a dye dilution method. RESULTS: Untreated control preparations produced fluid at 1.75 (0.33) ml/h per kg body weight, and did not change significantly in three hours; those immersed in 10(-12) M glucagon during the middle hour showed no significant change, but those given higher concentrations all showed significant reductions in fluid production or even reabsorption (65.6 (10.3)% fall at 10(-11) M, 70.0 (6.3)% fall at 10(-10) M, and 90.6 (11.1)% fall at 10(-9) M; based on 54 preparations). At 10(-9) M glucagon, 12 out of 30 preparations reabsorbed fluid. The linear log dose-response curve (r(2) = 0.94) gave a theoretical threshold at 4 x 10(-15) M glucagon. Responses appeared to involve the amiloride sensitive Na(+) based reabsorptive system: responses to 10(-9) M glucagon appeared to be reduced by 10(-6) M amiloride, and were abolished by 10(-5) M amiloride (based on 72 preparations). CONCLUSIONS: The results suggest that the surge of glucagon at birth may help to drain the lungs of fluid. As glucagon liberates cAMP, which also stimulates surfactant, glucagon is worth consideration for possible use in neonatal respiratory distress.