Influence of hypoxia on endothelin-1 binding sites in neonatal
porcine pulmonary vasculature.
Noguchi, Yasuzo, Alison A Hislop, and Sheila G Haworth.
Unit of Vascular Biology and Pharmacology, Institute of Child
Health, 30 Guilford Street, London WC1N 1EH
APStracts 3:0354H, 1996.
Exposure to chronic hypobaric hypoxia in the newborn piglet causes
pulmonary hypertension and structural abnormalities in the
intrapulmonary arteries which resemble those seen in babies with
pulmonary hypertension of the newborn. In order to investigate
whether the density and subtype of endothelin (ET) receptors in
intrapulmonary arteries was altered by exposure to to chronic
hypobaric hypoxia (50.8kPa) and changed on recovery, 125I ET-1
binding was studied using an in vitro autoradiographic technique on
67 piglets. Plasma ET was measured in 116 control, hypoxic and
recovery animals. In piglets exposed to hypoxia from birth plasma ET
was greater than normal for age (p<0.05), the binding density of
ET-1 was increased in elastic arteries, muscular arteries and veins
due to an increase in the density of ETA binding (p<0.05 for all
vessel types). On recovery plasma ET level became normal after 6
days. After 1 day of recovery the binding density of ET-1 and ETA was
normal in elastic arteries but was greater than normal in muscular
arteries even after 6 days (p<0.05). Exposure to hypoxia from 3
-6 or from 14-17 days did not alter the plasma ET and the binding
density in muscular arteries did not change but the density of
binding of ET-1, ETA and ETB in elastic pulmonary arteries decreased
(p<0.05). On recovery, it returned to normal by 6 days. In
summary, the increase in plasma ET and ET-1 and ETA binding density
suggest a role for endothelin in the pathogenesis of hypoxic
pulmonary hypertension in the newborn period. An initial normal
period of adaptation is protective.
Received 23 May 1996; accepted in final form 8 August 1996.
APS Manuscript Number H469-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996