Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung

• Published in: American journal of physiology. Lung cellular and molecular physiology 2007-05, Vol.292 (5), p.L1273-L1279
• Main Authors: Schindler, Margrid B, Hislop, Alison A, Haworth, Sheila G
• Format: Article
• Language: English
• Subjects: Aging - physiology; Amino acids; Animals; Animals, Newborn; Disease Models, Animal; Endothelin-1 - pharmacology; Fetus; Hogs; Hypertension; Hypoxia; Hypoxia - physiopathology; Lungs; Muscle, Smooth, Vascular - growth & development; Muscle, Smooth, Vascular - physiology; Muscle, Smooth, Vascular - physiopathology; Pulmonary arteries; Pulmonary Artery - drug effects; Pulmonary Artery - growth & development; Pulmonary Artery - physiology; Pulmonary Artery - physiopathology; Pulmonary Veins - drug effects; Pulmonary Veins - pathology; Pulmonary Veins - physiology; Pulmonary Veins - physiopathology; Swine
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00173.2006

Vascular Biology and Pharmacology Unit, Institute of Child Health, University College London, London, United Kingdom Submitted 11 May 2006 ; accepted in final form 1 January 2007 The response of pulmonary arteries to endothelin-1 (ET-1) changes with age in normal pigs and is abnormal in pulmonary hypertension. The purpose of this study was to determine if the same is true of the pulmonary veins. We studied the wall structure and functional response to ET-1 in pulmonary veins from normal pigs from fetal life to adulthood and from pigs subjected to chronic hypobaric hypoxia either from birth for 3 days or from 3 to 6 days of age. In isolated normal veins, the contractile response decreased by 40% between late fetal life and 14 days of age with a concomitant twofold increase in endothelium-dependent relaxant response. The ET A antagonist BQ-123 reduced the contractile response significantly more in newborn than older animals, whereas the ET-B antagonist BQ-788 had no effect in fetal animals and maximally increased contraction at 14 days of age. Hypoxic exposure significantly increased pulmonary vein smooth muscle area and contractile response to ET-1. The relaxation response was impaired following hypoxic exposure from birth but not from 3 to 6 days of age. The ET A antagonist BQ-123 decreased contractile and increased dilator responses significantly more than in age-matched controls. Thus pulmonary veins show age-related changes similar to those seen in the pulmonary arteries with a decrease in ET A -mediated contractile and increase in ET-B-mediated relaxant response with age. Contractile response was also increased in hypoxia as in the arteries. This study suggests that pulmonary veins are involved in postnatal adaptation and the pathogenesis of pulmonary hypertension. postnatal adaptation; pulmonary hypertension Address for reprint requests and other correspondence: M. B. Schindler, Paediatric Intensive Care Unit, Bristol Royal Hospital for Children, Upper Maudlin St., Bristol BS2 8BJ, United Kingdom (e-mail: Margrid.Schindler{at}ubht.nhs.uk )