Basic fibroblast growth factor and heparin cause endothelium-dependent dilation in coronary arterioles.
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In contrast to the well known angiogenic and mitogenic potential of fibroblast growth factors (FGF), their role in control of vascular tone is not known. The release of FGF from the cardiac extracellular matrix is facilitated by heparin, and heparin itself is known to bind to FGF receptors. Since FGF shares common signaling pathways with known vasodilatory compounds, we hypothesized that FGF and heparin produce vasoactive responses via common transduction mechanisms in coronary arterioles. Coronary arterioles (70-110 >im) were dissected from pig hearts and cannulated with micropipettes. Diameter was determined with videpmicroscopy in response to basic (b) and acidic (a) FGF in concentrations from 1-100 ng/ml and to heparin (20-200 U/ml). Basic FGF, but not aFGF, caused dose-dependent vasodilation with a maximum of 614% at the highest dose. Relaxation to bFGF could be nearly completely inhibited by pretreatment with L-NMMA (10 jiM, blockade of EDRF), but was not affected by pretreatment with indomethadn (1 o (iM, blockade of prostaglandins) or glibenclamide (10 uM, blockade of ATP-sensitive potassium channels). Interestingly, heparin caused dose-dependent vasodilation (threshold dose 20 U/ml) with a maximum of 1003% which was partially blocked by pretreatment with either L-NMMA or glibenclamide. Furthermore, the effect of bFGF could be completely blocked by pretreatment with an FGF receptor antibody and partially by pretreatment with a monoclonal antibody against FGF. Pretreatment with both antibodies partially inhibited also the effect of heparin. These results indicate that bFGF and heparin may be involved in the regulation of coronary microvascular tone acting partially through the same signaling mechanisms.
