Wu H M, Yuan Y, McCarthy M, Granger H J
Microcirculation Research Institute, Texas A & M University Health Science Center, Temple 76504, USA.
Am J Physiol. 1996 Sep;271(3 Pt 2):H1087-93. doi: 10.1152/ajpheart.1996.271.3.H1087.
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.
成纤维细胞生长因子（FGFs）已被公认为是血管内皮细胞增殖和血管生成的有效刺激因子。最近的实验证据表明，碱性成纤维细胞生长因子（bFGF）也参与动脉血压的调节。在本研究中，我们使用大鼠离体小动脉和完整的提睾肌，研究了酸性成纤维细胞生长因子（aFGF）和bFGF对肌肉微循环的影响。在离体微血管中，aFGF和bFGF（10⁻¹² - 10⁻⁸ M）以剂量和时间依赖性方式显著增加小动脉直径。在用NG-单甲基-L-精氨酸（L-NMMA，10⁻⁴ M）抑制一氧化氮合成时，这种作用被消除，但不受花生四烯酸代谢环氧化酶途径抑制剂吲哚美辛（10⁻⁴ M）的影响。在去内皮的血管中未观察到FGFs诱导的血管舒张。此外，我们使用活体显微镜研究了提睾肌中对生长因子反应的微血管血流动力学。aFGF和bFGF均使完整提睾肌的小动脉舒张，其模式与在离体小动脉中观察到的相似。在浓度为10⁻¹⁰ M时，aFGF使血管直径增加19%，血流量增加56%。给予L-NMMA可阻断FGF诱导的血管舒张和充血。这些结果表明，FGFs通过作用于小动脉内皮来调节骨骼肌中的血流。FGF诱导血管舒张的信号机制涉及小动脉内皮一氧化氮的合成。
