Hm. Wu et al., ACIDIC AND BASIC FGFS DILATE ARTERIOLES OF SKELETAL-MUSCLE THROUGH A NO-DEPENDENT MECHANISM, American journal of physiology. Heart and circulatory physiology, 40(3), 1996, pp. 1087-1093
Fibroblast growth factor (FGFs) have been known to be potent stimulato
rs of vascular endothelial cell proliferation and angiogenesis. Recent
experimental evidence indicates that basic FGF (bFGF) is also involve
d in modulation of arterial pressure. In this study, we investigated t
he effects of acidic FGF (aFGF) and bFGF on muscle microcirculation us
ing isolated arterioles and intact cremaster muscles of the rat. In is
olated microvessels, aFGF and bFGF (10(-12)-10(-8) M) significantly in
creased arteriolar diameter in a dose-dependent and time-dependent-man
ner. This effect was abolished during inhibition of nitric oxide synth
esis by N-G-monomethyl-L-arginine (L-NMMA, 10(-4) M) but was not affec
ted by indomethacin (10(-4) M), an inhibitor of the cyclooxygenase pat
hway of arachidonic acid metabolism. The vasodilation induced by FGFs
was not observed in endothelium-denuded vessels. Furthermore, we studi
ed microvascular hemodynamics in response to the growth factors in the
cremaster muscle using intravital microscopy. Both aFGF and bFGF dila
ted 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 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 s
ignaling mechanism of FGF-induced vasodilation involves the synthesis
of nitric oxide by arteriolar endothelium.