SUMMARY1. Exposure to glass of whole blood from anaesthetized foetal lambs (at 0-6-0-95 of term) causes the rapid development of a potent pulmonary vasodilator agent.2. The formation of the vasodilator agent on exposure to glass, its disappearance with time, and the inhibition of its production by soya bean trypsin inhibitor, suggest that it is bradykinin.3. Small doses of bradykinin (, 1 ng/kg) cause pulmonary vasodilatation on close arterial injection. Neither this, nor the vasodilatation caused by glass-exposed whole blood, are affected by agents which block the vasodilator actions of acetylcholine, isoprenaline or histamine.4. Exposure of foetal plasma and/or red cells to glass rarely caused the development of a pulmonary vasodilator agent. Maternal plasma was always active. Injection of the buffy coat from foetal blood caused pulmonary vasodilatation.5. The capacity of plasma from sheep at different ages to produce kinin(s) was examined by assay on the isolated rat's uterus. In the foetus activity was very low; it increased with age.6. In adolescent lambs 5-14 weeks after birth injection of 10 ng/kg bradykinin into the pulmonary artery caused only a trifling vasodilata-* Present address:
Lungs from fetal guinea pigs (54-67 days of gestation) were supported in vitro, and lung liquid secretion rates were measured by a dye-dilution technique. The average secretion rate in the first hour was 2.14 +/- 0.08 (SE) mL x kg-1 body weight.h-1 (0.21 +/- 0.01 mL/h) (n = 450); this was comparable to intact preparations. In an independent study of 30 lungs, secretion continued unchanged for 3 h, with no significant change in fluid composition. Between 54 days and term, production appeared to fall in terms of millilitres per kilogram per hour. The following agents were placed in the supporting saline during the middle hour of incubation. (i) Sodium iodoacetate: at 10(-4) M this produced a fall in secretion (fall, succeeding hours; 55.4 +/- 23.0 and 64.9 +/- 17.5%; n = 6); at 10(-3) M it stopped secretion (fall, succeeding hours; 87.2 +/- 10.3 and 100%, n = 6). (ii) Ouabain: at 10(-5) M there was no change in production (n = 6); at 10(-4) M, four preparations were unaffected, two reduced production. (iii) Epinephrine (10(-7) M) produced a significant fall in production in all cases (n = 6); in four preparations secretion reduced (average fall, 64.4 +/- 10.8%); in two preparations there was reabsorption (average rate, -1.03 mL.kg-1.h-1). This extends the effect of epinephrine to the guinea pig, and suggests that the in vitro preparation is a useful model for studies of the fetal lung.
The effects of arginine vasopressin (AVP) and amiloride were studied in 16 unanesthetized fetal sheep (129-135 days of age) with indwelling catheters. Secretion was measured by an impermeant tracer technique. Control fetuses showed no change in lung liquid secretion over a 5-h period with an average secretion rate of 3.6 +/- 0.31 ml.kg-1.h-1. Infusion of AVP (23.4 +/- 2.23 mU.kg-1.min-1) in seven fetuses (134-140 days of age) produced significant decreases (from control) in the secretion rate over a 5-h period: the secretion rate decreased by 68% in the last hour. Amiloride placed in the lung liquid during infusion of AVP, but after AVP effects had taken place, reversed the AVP-induced decrease in lung liquid secretion. AVP in conjunction with other hormones that are elevated during the stress of birth (epinephrine and cortisol) may be important in the removal of lung fluid at birth.
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