Farnesoid X receptor regulates vascular reactivity through nitric oxide mechanism.
Farnesoid X receptor (FXR), a ligand-activated transcription factor and a member of nuclear receptor family, is not only highly expressed in the adrenal cortex, intestine, kidney and liver, but also has recently been found in the vasculature. However, the evidence on the roles of FXR in the vasculature is limited and whether FXR regulates vascular reactivity is poorly understood. In present study, we investigated the expression of FXR protein in rat vasculature by immunohistochemical method and tested the effects of FXR activation by chenodeoxycholic acid (CDCA) on thoracic aortic contraction and dilation. We also detected the level of nitrite/nitrate (NOx) and superoxide in the thoracic aortic segments. We found that FXR was expressed in rat carotid arteries, thoracic aorta, abdominal aorta and femoral arteries. FXR activation by CDCA significantly (P<0.01) inhibited the contractile responses of rat thoracic aorta rings to KCl and phenylephrine. The cumulative concentrations of CDCA caused a concentration-dependent relaxation, which could be partly impaired by L-NAME, an inhibitor of nitric oxide (NO) synthase. The NOx content in thoracic aorta significantly (P<0.01) increased when treated with CDCA. Meanwhile, the vascular redox status was not altered by high concentration of CDCA. The present study suggested that FXR regulated vascular reactivity through NO mechanism, which merits further attention.
Insititute of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China.
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Zhang
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Ran
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Zhang
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Liu
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Huang
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D002536:Cerebral Arteries / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D005263:Femoral Artery / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D000099150:Receptor, Farnesoid X-Activated
D002635:Chenodeoxycholic Acid; D009566:Nitrates; D009569:Nitric Oxide; D009573:Nitrites; D018160:Receptors, Cytoplasmic and Nuclear; D013481:Superoxides; D000099150:Receptor, Farnesoid X-Activated