Effects of norepinephrine on lung liquid production by in vitro lungs from fetal guinea pigs

Abstract

Lungs from near-term fetal guinea pigs (61 ± 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Untreated control preparations produced fluid at 1.38 ± 0.30 mL·kg-1 body weight·h-1, with no significant change (ANOVA; regression analysis); those given 1.24 × 10-9 or 1.24 × 10-8 M norepinephrine during the middle hour showed no significant change, but those given concentrations between 5.24 × 10-8 and 1.24 × 10-5 M all showed significant reductions or fluid reabsorption (based on 42 fetuses). The responses showed a linear relationship with the log concentration (r = 0.97). They appeared to involve alpha-adrenoreceptors, since responses to 10-7 M norepinephrine were unaffected by 10-6 M propranolol, but those to 10-7 and 1.24 × 10-6 M norepinephrine were abolished by 10-6 and 1.78 × 10-5 M phentolamine, respectively (based on 48 fetuses). Activation was through alpha2-adrenoreceptors, since responses to 10-7 and 10-5 M norepinephrine were abolished by 10-4 M yohimbine, but not by 10-5 M prazosin (based on 60 fetuses). The results show that norepinephrine is able to reduce lung liquid production when at plasma levels present at birth, and that it can produce reabsorption; unlike epinephrine, there was no reduction in responses at high concentrations. This work reintroduces a neglected factor, norepinephrine, into possible controls of lung liquid reabsorption, and opens up the potential for neural controls.Key words: fetus, norepinephrine, adrenoreceptors, lung liquid.