Neurotrophins in pulmonary artery smooth muscle

Abstract

Neurotrophins are growth factors traditionally associated with neuronal structure and function; however, neurotrophins and their receptors have been found throughout the lung, including airway, pulmonary artery and endothelium although their roles within the lung are still under investigation. We tested the hypothesis that brain derived neurotrophic factor (BDNF) enhances pulmonary artery constriction. In endothelium‐intact arterial rings, BDNF (acute 10nM, 1h; chronic 1nM, 18h) did not affect phenylephrine‐induced contraction, but enhanced subsequent ACh‐induced relaxation. These effects were blunted by endothelium‐denudation. In fura‐2 loaded human pulmonary artery smooth muscle cells, acute and chronic BDNF decreased the Ca2+ responses to 10 μM bradykinin. In human pulmonary artery exposed to TNFα (50 ng/mL, 18h), BDNF levels were decreased, compared to human airway, where previous studies under identical treatment resulted in increased levels. These data refute our hypothesis and suggest that neurotrophins, working via endothelial cells, enhance vasodilation in the pulmonary vasculature.Supported by FAMRI, NIH grant UL1RR024150, and the Department of Anesthesiology, Mayo Clinic.