Regulation of pulmonary vasoconstriction by agonists and caveolae

Christian Schach, Amy L. Firth, Minlin Xu, Carmelle V. Remillard, Hemal H. Patel, Paul A. Insel, Jason X.J. Yuan

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Sustained pulmonary vasoconstriction contributes to the elevated pulmonary vascular resistance observed in pulmonary arterial hypertension. A rise in cytosolic Ca2 + in pulmonary artery smooth muscle cells (PASMCs) is major trigger for pulmonary vasoconstriction. One family of drugs currently being pursued as a potential treatment for pulmonary hypertension are the statins, which act by depleting cholesterol and reducing the number of caveolae. This study aimed at investigating the role of caveolae, membrane receptors, and ion channels (that are potentially located in the caveolae) in agonist-mediated pulmonary vasoconstriction in order to gain a greater understanding of the signaling mechanisms involved in the regulation of pulmonary vascular tone. Chronic treatment of PASMCs with the cholesterol-depleting agent, methyl-β-cyclodextrin (Mβ CD), significantly reduced the number of cholesterol rich caveolae regions in the membrane. This disruption of cholesterol in caveolae significantly inhibited pharmacomechanical (induced by phenylephrine), but not electromechanical (induced by elevated extracellular potassium concentration), rat pulmonary artery contraction. These results indicate that receptors may functionally colocalize in caveolae in PASMCs and coordinate to regulate pulmonary vascular tone.

Original languageEnglish (US)
Pages (from-to)195-208
Number of pages14
JournalExperimental Lung Research
Volume34
Issue number4
DOIs
StatePublished - May 1 2008
Externally publishedYes

Keywords

  • Caveolae
  • Pulmonary artery
  • Store depletion
  • Vasoconstriction

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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  • Cite this

    Schach, C., Firth, A. L., Xu, M., Remillard, C. V., Patel, H. H., Insel, P. A., & Yuan, J. X. J. (2008). Regulation of pulmonary vasoconstriction by agonists and caveolae. Experimental Lung Research, 34(4), 195-208. https://doi.org/10.1080/01902140801925471