Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 668, Issue 3, Pages 401-406Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2011.07.040
Keywords
Endothelium; Relaxation; Growth factor; Nitric oxide; Organ culture
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Funding
- Kitasato University, School of Veterinary Medicine
- Kitasato University
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Organ culture of blood vessels provides a useful technique to investigate long-tern, effects of drugs because tissue architecture and function are well preserved. Various growth factors are responsible for structural and functional changes during vascular diseases. We investigated long-term effects of fetal bovine serum (FBS) which contains such factors on endothelium-dependent relaxation using organ-culture method. Rat isolated mesenteric arteries with endothelium were cultured for 3 days without or with 10% FBS (FBS). Acetylcholine- and bradykinin-induced endothelium-dependent relaxations were significantly impaired in FBS, whereas sodium nitroprusside-induced relaxation of endothelium-removed artery was unchanged. Morphological examination revealed that endothelium was intact in FBS. Acetylcholine-induced nitric oxide (NO) release as detected by 4, 5-diaminofluorescein significantly decreased in FBS, whereas endothelial NO synthase expression was unchanged. A Ca2+ ionophore, A23187-induced relaxation was unchanged in FBS. A phospholipase C activator, m-3M3FBS-induced relaxation of FBS was unchanged in either Ca2+-containing or -free solution. Total expressions of transient receptor potential canonical channels (TRPCs: TRPC-1, -4, -5) were similar in FBS. These data suggest that FBS impairs endothelium-dependent relaxation by inhibiting events upstream of phospholipase C activation including phospholipase C, G-protein, and receptors in endothelium. (C) 2011 Elsevier B.V. All rights reserved.
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