Dexamethasone prevents impairment of endothelium-dependent relaxation in arteries cultured with fetal bovine serum.

Abstract

In the present study, we assessed the effects of dexamethasone on fetal bovine serum-induced dysfunction of mesenteric endothelial cells using an organ culture procedure. In rabbit mesenteric arteries cultured in the presence of 10% fetal bovine serum for 7 days, the endothelium-dependent, nitric oxide (NO)-mediated relaxations caused by substance P and ionomycin were decreased as compared to those in non-treated arteries. Dexamethasone (3 microM) inhibited the proliferative stimuli-induced endothelial dysfunction without affecting the contractility or NO susceptibility of smooth muscle cells. Cross-sectioned hematoxylin-eosin staining and whole-mount CD31 staining indicated that chronic proliferative stimulation induced detachment of endothelial cells from the tunica intima in some regions, and also caused thickening of the arterial wall and shortening of the internal diameter. Endothelial NO synthesis (eNOS) mRNA expression was also decreased by the treatment with fetal bovine serum. The dexamethasone treatment did not inhibit the smooth muscle hypertrophy, but it inhibited the peeling of endothelial cells and recovered the eNOS mRNA expression. These results suggest that DEX ameliorate the impairments of arterial relaxation induced by proliferative stimuli and that these beneficial effects may be mediated by maintaining the adhesion of endothelial cells to the vascular wall and/or by recovering eNOS mRNA expression.

• Authors: Takahisa Murata, Natsuko Suzuki, Hideyuki Yamawaki, Koichi Sato, Masatoshi Hori, Hideaki Karaki, Hiroshi Ozaki
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 515 Issue 1-3 Pg. 134-41 (May 16 2005) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15907323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Serum-Free
• Platelet Endothelial Cell Adhesion Molecule-1
• RNA, Messenger
• Vasodilator Agents
• Nitroprusside
• Potassium Chloride
• Dexamethasone
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type III

Topics

• Animals
• Cattle
• Culture Media, Serum-Free (pharmacology)
• Dexamethasone (pharmacology)
• Endothelium, Vascular (chemistry, drug effects, physiopathology)
• Fetal Blood
• Gene Expression Regulation, Enzymologic (drug effects)
• Immunohistochemistry
• Male
• Mesenteric Arteries (drug effects, metabolism, physiopathology)
• Microscopy, Confocal
• Muscle Contraction (drug effects)
• Muscle, Smooth, Vascular (drug effects, physiology)
• Nitric Oxide Synthase (genetics)
• Nitric Oxide Synthase Type III
• Nitroprusside (pharmacology)
• Organ Culture Techniques (methods)
• Platelet Endothelial Cell Adhesion Molecule-1 (analysis)
• Potassium Chloride (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Rabbits
• Reverse Transcriptase Polymerase Chain Reaction
• Vasodilation (drug effects)
• Vasodilator Agents (pharmacology)