p75 neurotrophin receptor regulates agonist-induced pulmonary vasoconstriction

Minlin Xu, Carmelle V. Remillard, Benjamin D. Sachs, Ayako Makino, Oleksandr Platoshyn, Weijuan Yao, Wolfgang H. Dillmann, Katerina Akassoglou, Jason X.J. Yuan

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

A member of the TNF receptor family, the p75 neurotrophin receptor (p75NTR) has been previously shown to play a role in the regulation of fibrin deposition in the lung. However, the role of p75NTR in the regulation of pulmonary vascular tone in the lung is unknown. In the present study, we evaluated the expression of p75NTR in mouse pulmonary arteries and the putative role of p75NTR in modulating pulmonary vascular tone and agonist responsiveness using wild-type (WT) and p75 NTR knockout (p75-/-) mice. Our data indicated that p75NTR is expressed in both smooth muscle and endothelial cells within the pulmonary vascular wall in WT mice. Pulmonary artery rings from p75-/- mice exhibited significantly elevated active tension due to endothelin-1-mediated Ca2+ influx. Furthermore, the contraction due to capacitative Ca 2+ entry (CCE) in response to phenylephrine-mediated active depletion of intracellular Ca2+ stores was significantly enhanced compared with WT rings. The contraction due to CCE induced by passive store depletion, however, was comparable between WT and p75-/- rings. Active tension induced by serotonin, U-46619 (a thromboxane A2 analog), thrombin, 4-aminopyridine (a K+ channel blocker), and high extracellular K 9 in p75-/- rings was similar to that in WT rings. Deletion of p75NTR did not alter pulmonary vasodilation to sodium nitroprusside (a nitric oxide donor). These data suggest that intact p75 NTR signaling may play a role in modulating pulmonary vasoconstriction induced by endothelin-1 and by active store depletion.

Original languageEnglish (US)
Pages (from-to)H1529-H1538
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number4
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Keywords

  • Mouse
  • Pharmacology
  • Pulmonary artery
  • Store depletion
  • Vasoconstriction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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