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Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18710-5. doi: 10.1073/pnas.1308130110. Epub 2013 Oct 28.

Endocannabinoid anandamide mediates hypoxic pulmonary vasoconstriction.

Author information

1
Institutes of Physiology I and Molecular Psychiatry, Life and Brain Center, University of Bonn, 53127 Bonn, Germany.

Abstract

Endocannabinoids are important regulators of organ homeostasis. Although their role in systemic vasculature has been extensively studied, their impact on pulmonary vessels remains less clear. Herein, we show that the endocannabinoid anandamide (AEA) is a key mediator of hypoxic pulmonary vasoconstriction (HPV) via fatty acid amide hydrolase (FAAH)-dependent metabolites. This is underscored by the prominent vasoconstrictive effect of AEA on pulmonary arteries and strongly reduced HPV in FAAH(-/-) mice and wild-type mice upon pharmacological treatment with FAAH inhibitor URB597. In addition, mass spectrometry measurements revealed a clear increase of AEA and the FAAH-dependent metabolite arachidonic acid in hypoxic lungs of wild-type mice. We have identified pulmonary vascular smooth muscle cells as the source responsible for hypoxia-induced AEA generation. Moreover, either FAAH(-/-) mice or wild-type mice treated with FAAH inhibitor URB597 are protected against hypoxia-induced pulmonary hypertension and the concomitant vascular remodeling in the lung. Thus, the AEA/FAAH pathway is an important mediator of HPV and is involved in the generation of pulmonary hypertension.

KEYWORDS:

cannabinoid; pulmonary vascular tone

PMID:
24167249
PMCID:
PMC3831960
DOI:
10.1073/pnas.1308130110
[Indexed for MEDLINE]
Free PMC Article

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