Postnatal changes in beta-adrenoceptors in the lung and the effect of hypoxia induced pulmonary hypertension of the newborn.
1. beta-adrenoceptor activation leads to pulmonary vasodilatation. The increase in circulating catecholamines at birth may assist the postnatal fall in vascular resistance by their activation. To study beta(1)- and beta(2)-adrenoceptors during postnatal adaptation, we used [(125)I]-iodocyanopindolol (ICYP) binding to lung membranes and sections to quantify and locate the binding sites in piglets from birth to 14 days of age and compared them with those in adult pigs. In addition, pulmonary hypertension was induced in newborn piglets by hypobaric hypoxia. 2. In lung membranes the equilibrium dissociation constant (K(d)) did not change with age for total beta-adrenoceptors or for beta(2)-adrenoceptors, but there was a significant increase in maximum binding sites (B(max)) between birth and 3 days of age. On tissue sections, B(max) increased between 3 days and adulthood with no change in K(d). 3. Binding sites of beta(1)- and beta(2)-adrenoceptors were localized to the bronchial epithelium, to endothelium of extra- and intra-pulmonary arteries and to lung parenchyma. Total beta-adrenoceptor density increased with age at all locations (P<0.05 - 0.01). At birth intrapulmonary arteries showed no binding, beta(2)-adrenoceptors appeared on day 1 and increased up to 14 days of age. beta(1)-adrenoceptors appeared by 3 days of age and increased with age. 4. Hypobaric hypoxia from birth led to attenuation in the normal postnatal increase in receptor number, but hypoxia from 3 - 6 days did not decrease receptor density. 5. The normal postnatal increase in beta-adrenoceptors suggests a potential for catecholamine induced dilatation in the lung during adaptation which is attenuated in pulmonary hypertension.
Hislop
Alison A
AA
Vascular Biology and Pharmacology Unit, Institute of Child Health, London, UK. a.hislop@ich.ucl.ac.uk
Mak
Judith C W
JC
Kelly
David
D
Reader
Jayne A
JA
Barnes
Peter J
PJ
Haworth
Sheila G
SG
D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001665:Binding Sites / Q000502:physiology; D005260:Female; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008168:Lung / Q000254:growth & development / Q000378:metabolism*; D011247:Pregnancy; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013552:Swine
D011943:Receptors, Adrenergic, beta