Vasodilatory effect of basic fibroblast growth factor in isolated rat cerebral arterioles: mechanisms involving nitric oxide and membrane hyperpolarization.
Basic fibroblast growth factor (bFGF), a potent mitogen, acutely dilates cerebral blood vessels and may be effective in reducing cerebral infarction. However, the vasodilatory mechanism, which may involve nitric oxide (NO), is not completely understood. This study investigated whether membrane hyperpolarization is also involved in this mechanism. Membrane potential (MP) of smooth muscle cells and vessel diameter of isolated intracerebral arterioles were simultaneously measured following extraluminal application of bFGF in rats. The involvement of NO and adenosine triphosphate-sensitive potassium (KATP) channels in bFGF-induced vasodilation and membrane hyperpolarization was evaluated using specific inhibitors, NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) and glibenclamide (GB, 10(-5) M), respectively. The resting MP was recorded at a mean value of -31.9 +/- 4.5 mV. bFGF (1 to 1000 ng/ml) produced significant vasodilation and hyperpolarization. Treatment with L-NMMA caused vasoconstriction and significantly attenuated bFGF-induced vasodilation without affecting membrane hyperpolarization. In the presence of GB, the membrane potential was significantly depolarized but the vessel diameter was only marginally reduced, so bFGF-induced membrane hyperpolarization was inhibited while arteriolar dilation was attenuated. These results suggest that bFGF-induced vasodilation is mediated by a mechanism involving both NO and membrane hyperpolarization, and that membrane hyperpolarization is caused by the activation of KATP channels.
Kajita
Y
Y
Department of Neurosurgery, Nagoya University School of Medicine, Nagoya.
Takayasu
M
M
Yoshida
J
J
Dietrich
H H
HH
Dacey
R G
RG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002536:Cerebral Arteries / Q000502:physiology*; D004594:Electrophysiology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D015221:Potassium Channels; D016222:Fibroblast Growth Factor 2; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D005905:Glyburide