Role of tyrosine kinase in dilator responses of rat basilar artery in vivo.
We tested the hypothesis that dilator responses of the basilar artery to endothelium-dependent vasodilators are mediated by activation of tyrosine kinase in vivo. Using a cranial window in anesthetized rats, we examined responses of the basilar artery to acetylcholine and bradykinin. Topical application of acetylcholine and bradykinin increased diameter of the basilar artery in a concentration-related manner. Genistein, an inhibitor of tyrosine kinase, did not affect baseline diameter of the basilar artery but inhibited vasodilatation in response to acetylcholine and bradykinin, without affecting vasodilatation produced by sodium nitroprusside. Tyrphostin 47, another inhibitor of tyrosine kinase, attenuated acetylcholine-induced dilatation of the basilar artery without affecting vasodilatation in response to sodium nitroprusside. Tyrphostin 63, an inactive analogue of tyrphostin 47, did not affect acetylcholine-induced vasodilatation. Sodium orthovanadate, an inhibitor of tyrosine phosphatase, enhanced acetylcholine-induced dilatation of the basilar artery. These results suggest that dilator responses of the basilar artery to endothelium-dependent agonists, acetylcholine and bradykinin, are mediated in large part by activation of tyrosine kinase. Because vasodilatation produced by these agonists is mediated primarily by nitric oxide, activation of tyrosine kinase may have an important role in nitric oxide production in the basilar artery in vivo.
Kitazono
T
T
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. kitazono@intmed2.med.kyushu-u.ac.jp
Ibayashi
S
S
Nagao
T
T
Fujii
K
K
Kagiyama
T
T
Fujishima
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000201:enzymology; D001920:Bradykinin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020032:Tyrphostins; D014638:Vanadates / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009570:Nitriles; D010636:Phenols; D020032:Tyrphostins; D014665:Vasodilator Agents; C060152:tyrphostin 47; D009599:Nitroprusside; D014638:Vanadates; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D000109:Acetylcholine; D001920:Bradykinin