EPINEPHRINE-INDUCED PULMONARY-EDEMA IN RATS IS INHIBITED BY CORTICOTROPIN-RELEASING FACTOR

In various animal models of injury to skin, mucous membranes, muscle and brain, corticotropin-releasing factor (CRF) attenuated vascular leakage in the injured tissues. Here, the effects of CRF on a rat model of pulmonary oedema were examined. Male albino rats (220-290 g) received saline or CRF s.c., 30 min before pentobarbital anaesthesia, 60 mg/kg i.p., and 1 h before 1-epinephrine bitartrate (Epi), 30μg/kg i.v. Within 30 min after Epi all (n=27) saline-pretreated rats were dead from pulmonary oedema, but animals receiving human/rat CRF at doses of 7 to 57 μg/kg s.c. (n=25) were all alive. Body wt, wet and dry wt of lungs were used to calculate an oedema index. This index increased from 3.6±0.1 to 9.6±0.3 after Epi but was inhibited by 87% after CRF 28 μg/kg s.c. The ED50 of CRF for reducing pulmonary oedema was 3.2 (1.3-7.4) μg/kg s.c. Mean arterial pressure increased from 119±4 to 167±2 mmHg after Epi 10 μg/kg i.v., but was not different (118±3 to 169±4 mmHg) after CRF pretreatment, 6 μg/kg s.c., a dose which reduced lung oedema. Pharmacokinetic estimates suggest that plasma levels of CRF sufficient to attenuate lung oedema in rats approximate those seen in pregnant women at delivery, raising the possibility that endogenous CRF may protect the maternal organism during parturition. © 1992.