Endothelial dysfunction and altered bradykinin response due to oxidative stress induced by serum deprivation in the bovine cerebral artery.
Oxidative stress plays a critical role in the pathogenesis of vasospasm after a subarachnoid hemorrhage. We demonstrate that 24-h incubation of the isolated bovine middle cerebral arteries in the serum-free media at 37 degrees C converted the response to bradykinin from relaxation to contraction, in a manner sensitive to free radical scavengers. In the freshly prepared strips, bradykinin induced an endothelium-dependent relaxation, while having no direct effect on the smooth muscle. However, in the strips treated in serum-free media, bradykinin failed to induce endothelium-dependent relaxation, but did demonstrate a direct contractile effect on smooth muscle. The addition of superoxide dismutase and ascorbic acid or 5% serum during the 24-h incubation in the serum-free media prevented the loss of endothelium-dependent relaxation and the development of a contractile response to bradykinin. SB203580 (4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole), a p38 mitogen-activated protein kinase inhibitor, and genistein (4',5,7-Trihydroxyisoflavone), a tyrosine kinase inhibitor, also demonstrated a similar preventive effect. In conclusion, serum-deprivation induced endothelial dysfunction and the responsiveness of smooth muscle to bradykinin due to failure of eliminating oxidative stress. p38 mitogen-activated protein kinase and tyrosine kinase were suggested to play a critical role in this endothelial dysfunction.
Maeda
Yoshihisa
Y
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Hirano
Katsuya
K
Nishimura
Junji
J
Sasaki
Tomio
T
Kanaide
Hideo
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects* / Q000503:physiopathology; D002867:Chromones / Q000494:pharmacology; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D018384:Oxidative Stress; D011188:Potassium / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011725:Pyridines / Q000494:pharmacology; D044967:Serum / Q000737:chemistry; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D000577:Amides; D002867:Chromones; D003470:Culture Media; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005419:Flavonoids; D016166:Free Radical Scavengers; D007093:Imidazoles; D007211:Indoles; D008301:Maleimides; D009025:Morpholines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014662:Vasoconstrictor Agents; C108830:Y 27632; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019833:Genistein; D013482:Superoxide Dismutase; C070515:bisindolylmaleimide I; C093642:SB 203580; D001205:Ascorbic Acid; D011188:Potassium; D001920:Bradykinin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one