TY - JOUR
T1 - Vasodilatory effect of basic fibroblast growth factor in isolated rat cerebral arterioles
T2 - Mechanisms involving nitric oxide and membrane hyperpolarization
AU - Kajita, Yasukazu
AU - Takayasu, Masakazu
AU - Yoshida, Jun
AU - Dietrich, Hans H.
AU - Dacey, Ralph G.
PY - 2001
Y1 - 2001
N2 - 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 (K ATP) channels in bFGF-induced vasodilation and membrane hyperpolarization was evaluated using specific inhibitors, N G-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 K ATP channels.
AB - 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 (K ATP) channels in bFGF-induced vasodilation and membrane hyperpolarization was evaluated using specific inhibitors, N G-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 K ATP channels.
KW - Basic fibroblast growth factor
KW - Cerebral arterioles
KW - Glibenclamide
KW - Membrane potential
KW - N -monomethyl-L-arginine
KW - Vasodilation
UR - http://www.scopus.com/inward/record.url?scp=0035021224&partnerID=8YFLogxK
U2 - 10.2176/nmc.41.177
DO - 10.2176/nmc.41.177
M3 - Article
C2 - 11381676
AN - SCOPUS:0035021224
SN - 0470-8105
VL - 41
SP - 177
EP - 185
JO - Neurologia Medico-Chirurgica
JF - Neurologia Medico-Chirurgica
IS - 4
ER -