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This Article Full Text Full Text (PDF) All Versions of this Article: 296/1/L115    most recent 90391.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Farah, O. R. Articles by Belik, J. Search for Related Content PubMed PubMed Citation Articles by Farah, O. R. Articles by Belik, J.

Airway epithelial-derived factor relaxes pulmonary vascular smooth muscle

Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, and the Departments of Paediatrics and Physiology, University of Toronto, Toronto, Ontario, Canada

Submitted 22 July 2008 ; accepted in final form 20 October 2008

The factors controlling the pulmonary vascular resistance under physiological conditions are poorly understood. We have previously reported on an apparent cross talk between the airway and adjacent pulmonary arterial bed where a factor likely derived from the bronchial epithelial cells reduced the magnitude of agonist-stimulated force in the vascular smooth muscle. The main purpose of this investigation was to evaluate whether bronchial epithelial cells release a pulmonary arterial smooth muscle relaxant factor. Conditioned media from SPOC-1 or BEAS-2B, a rat- and a human-derived bronchial epithelial cell line, respectively, were utilized. This media significantly relaxed precontracted adult but not fetal pulmonary arterial muscle in an oxygen tension-dependent manner. This response was mediated via soluble guanylate cyclase, involving AKT/PI3-kinase and neuronal nitric oxide synthase. Airway epithelial cell-conditioned media increased AKT phosphorylation in pulmonary smooth muscle cells (SMC) and reduced intracellular calcium change following ATP stimulation to a significantly greater extent than observed for bronchial SMC. The present data strongly support the evidence for bronchial epithelial cells releasing a stable and soluble factor capable of inducing pulmonary arterial SMC relaxation. We speculate that under physiological conditions, the maintenance of a low pulmonary vascular resistance, postnatally, is in part modulated by the airway epithelium.

pulmonary hypertension; pulmonary vascular resistance; fetal; hypoxic pulmonary vasoconstriction response