Acidic and basic FGFs dilate arterioles of skeletal muscle through a NO-dependent mechanism.
Fibroblast growth factors (FGFs) have been known to be potent stimulators of vascular endothelial cell proliferation and angiogenesis. Recent experimental evidence indicates that basic FGF (bFGF) is also involved in modulation of arterial pressure. In this study, we investigated the effects of acidic FGF (aFGF) and bFGF on muscle microcirculation using isolated arterioles and intact cremaster muscles of the at. In isolated microvessels, aFGF and bFGF (10(-12)-10(-8) M) significantly increased arteriolar diameter in a dose-dependent and time-dependent manner. This effect was abolished during inhibition of nitric oxide synthesis by NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) but was not affected by indomethacin (10(-4) M), an inhibitor of the cyclooxygenase pathway of arachidonic acid metabolism. The vasodilation induced by FGFs was not observed in endothelium-denuded vessels. Furthermore, we studied microvascular hemodynamics in response to the growth factors in the cremaster muscle using intravital microscopy. Both aFGF and bFGF dilated arterioles of the intact cremaster muscle in a pattern similar to that observed in the isolated arterioles. At a concentration of 10(-10) M, aFGF caused a 19% increase in vessel diameter and 56% increase in blood flow. Administration of L-NMMA blocked by FGF-induced vasodilation and hyperemia. These results suggest that FGFs modulate blood flow in the skeletal muscle by acting on the endothelium of arterioles. The signaling mechanism of FGF-induced vasodilation involves the synthesis of nitric oxide by arteriolar endothelium.
Wu
H M
HM
Microcirculation Research Institute, Texas A & M University Health Science Center, Temple 76504, USA.
Yuan
Y
Y
McCarthy
M
M
Granger
H J
HJ
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D014665:Vasodilator Agents; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D009569:Nitric Oxide