Postnatal changes in β‐adrenoceptors in the lung and the effect of hypoxia induced pulmonary hypertension of the newborn

Abstract

1 b-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 b 1 -and b 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 b-adrenoceptors or for b 2 -adrenoceptors, but there was a signi®cant 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 b 1 -and b 2 -adrenoceptors were localized to the bronchial epithelium, to endothelium of extra-and intra-pulmonary arteries and to lung parenchyma. Total b-adrenoceptor density increased with age at all locations (P50.05 ± 0.01). At birth intrapulmonary arteries showed no binding, b 2 -adrenoceptors appeared on day 1 and increased up to 14 days of age. b 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 b-adrenoceptors suggests a potential for catecholamine induced dilatation in the lung during adaptation which is attenuated in pulmonary hypertension.

Spatiotemporal Changes in the Gene Expression Spectrum of the β2 Adrenergic Receptor Signaling Pathway in the Lungs of Rhesus Monkeys

“…The main function of ADRB2 in ASM cells is to relax the airway [ 4 ]. These findings suggest that PNMT and ADRB2 activate the Gs–AC–PKA signaling pathway to cause airway dilation, thereby ensuring optimal ventilation in the lungs [ 20 ]. Furthermore, we found elevated expression of both PNMT and ADRB2 in the late gestational stage; therefore, we speculate that this adrenergic mechanism also applies to premature infants.…”

Adrenergic receptor genotypes influence postoperative outcomes in infants in the Single-Ventricle Reconstruction Trial

“…4 Adrenergic upregulation is an important mechanism of cardiovascular adaptation during stress particularly in the infant where the circulation is highly catecholamine-dependent. 5, 6 While acute upregulation is compensatory, chronic upregulation can have detrimental effects by increasing systemic and pulmonary vascular resistance, and increasing myocardial oxygen demands, resulting in adverse cardiac remodeling and ventricular dysfunction. 4, 7–12 In children with dilated cardiomyopathy, α2 and β1 upregulation and β2 downregulation genotypes were associated with worse ventricular function, heart failure progression and acute hemodynamic decompensation.…”