SUMMARY1. In the chronically catheterized fetal lamb, intravenous infusion of adrenaline at 0 5 jug/min produced slowing of the secretion of lung liquid or its absorption, an effect which increased exponentially with advancing gestation. Between 120 and 130 days, the characteristic response was slowing of secretion, whereas after 130 days it was absorption.2. Stimulus-response curves, relating secretion or absorption rate to plasma adrenaline concentration, were obtained by infusing adrenaline into the fetus intravenously at rates between 0-1 and 1.0 #sg/min (0-55-5 5 nmol/min). These curves allowed estimation of the minimum concentration of adrenaline required to inhibit secretion ([Ai]) and this was found to decrease from 0-43 ng/ml. (2-35 nM) at 132-4 days' gestation to 0-029 ng/ml. (0 16 nM) at gestations above 140 days.3. During spontaneous labour there was a slowing of lung liquid secretion in the early stages followed by absorption during the last 50-150 min. The mean concentration of adrenaline in plasma increased from 0-087 ng/ml. (048 nM) in early labour to 6-86 ng/ml. (37 5 nM) in the last 50 min and to 7-17 ng/ml. (39-2 nM) in the early post-natal period. Mean noradrenaline levels at the same times were 1-71 ng/ml.(10-1 nM), 12-14 ng/ml. (71'8 nM) and 9-10 ng/ml. (53 9 nM). The relationship between the plasma adrenaline concentration and the rate of absorption during labour was similar to that found when adrenaline was infused at various rates into the non-labouring fetus of comparable gestational age.4. The upper airway of the fetus was shown to be capable of acting as a one-way valve allowing outflow but not inflow of liquid. Thus withdrawal of liquid at 5-20 ml./hr from the fetal trachea below the larynx caused closure of the upper airway and this result was obtained both when the recurrent laryngeal nerves were intact and when they were divided.

To determine whether epinephrine-induced hypokalemia is due to beta2-adrenoceptor stimulation, and whether hypokalemia can occur at physiologic concentrations of the agonist, epinephrine was infused into six normal volunteers at a rate of 0.1 microgram per kilogram of body weight per minute. The circulating epinephrine concentration was increased to 1.74 +/- 0.65 ng per milliliter, plasma potassium was reduced by 0.82 +/- 0.19 meq per liter, plasma insulin fell by 12 +/- 4 mU per liter, plasma renin activity was elevated, and tachycardia occurred. Isoproterenol infused at 0.02 micrograms per kilogram per minute caused similar tachycardia (25 beats per minute) and elevation in plasma renin activity (6.0 to 6.5 ng per milliliter per hour), but no hypokalemia. The difference in responses to the two catecholamines was ascribed to the relative beta2-selectivity of epinephrine. This hypothesis was tested in six subjects given infusions of epinephrine (0.05 micrograms per kilogram per minute) after administration of either 2.5 or 5 mg of ICI 118551--a selective beta2-receptor antagonist--or placebo. After placebo, epinephrine infusion elevated the circulating epinephrine concentration and reduced plasma potassium; hypokalemia was prevented by the beta2-antagonist. This drug only partially inhibited the rises in plasma renin and glucose and the shortening of systolic time intervals; there was no tachycardia. Fifteen-fold to 30-fold increases in circulating epinephrine concentration appear to cause hypokalemia by a specific beta2-receptor effect distinct from other actions of epinephrine. This phenomenon may be of physiologic importance after severe myocardial infarction, when similar increases in plasma epinephrine have occurred.

SUMMARY1. In fetal sheep at 113-120 days' gestation, thyroidectomy was performed and tracheal, arterial and venous catheters inserted. Following a recovery period experiments were performed from 120-145 days to measure changes in lung liquid secretion or its absorption in response to i.v. adrenaline infusion or to introduction of dibuteryl cyclic AMP into lung liquid. The results were compared with those previously obtained in non-thyroidectomized fetuses.2. Plasma levels of thyroid hormones in non-thyroidectomized fetuses confirmed the pattern found by previous workers. In thyroidectomized fetuses the levels of thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) were very low except in one fetus which showed biochemical evidence of thyroid regeneration towards the end of gestation.3. In thyroidectomized fetuses the normal response to adrenaline infusion (diminution of reversal of lung liquid secretion) was profoundly suppressed and very little gestational maturation in this response took place, except in the one fetus with evidence of thyroid regeneration in which a normal reabsorptive response developed in late gestation.4. In thyroidectomized fetuses, the normal response to dibuteryl cyclic AMP was greatly reduced and its increase with gestation which normally parallels that seun during adrenaline infusion did not take place.

Plasma catecholamine concentrations were measured in 15 patients (six male) aged 14-63 years attending the casualty department with acute severe asthma (peak expiratory flow 27% (SEM 3%) of predicted). Nine patients were admitted and six were not. The plasma noradrenaline concentration, reflecting sympathetic nervous discharge, was two to three times normal In all patients and was significantly higher in those who required admission compared with those discharged home (mean 7-7 (SEM 0-6) v 4-7 (0-5) nmol/l (1-3 (SEM 0-1) v 0-8 (0-08) ng/ml); p <0 001). Plasma adrenaline concentradon, however, was not. increased in any patient. This surprising failure of the plasma adrenaline concentration to increase during the stress of an acute attack of asthma was unexplained and contrasts with the pronounced rise in plasma adrenaline and noradrenaline concentrations in acute myocardial infarction, heart failure, and septicaemia.