Basic FGF reduces stunning via a NOS2-dependent pathway in coronary-perfused mouse hearts

Basic FGF reduces stunning via an NOS2-dependent pathway in coronary-perfused mouse hearts. Am J Physiol Heart Circ Physiol 279: H260-H268, 2000.--Basic fibroblast growth factor (FGF-2) may protect the heart from ischemia-reperfusion injury (stunning) by stimulating nitric oxide (NO) production. To test this hypothesis, we pretreated coronary-perfused mouse hearts with 1 [micro]g/ml FGF-2 or vehicle control before the onset of ischemia. Intracellular calcium [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] was estimated by aequorin, and NO release was measured with an NO-selective electrode. Hearts perfused with FGF-2 maintained significantly better left ventricular (LV) function during ischemia than hearts perfused with vehicle. FGF-2 significantly delayed the onset of ischemic contracture and improved LV recovery during reperfusion. [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] was similar in both groups at baseline during ischemia and reperfusion. L-[N.sup.6]-(1-iminoethyl)lysine, a selective inhibitor of inducible NO synthase (NOS2), obliterated the protective effects of FGF-2. In transgenic hearts deficient in the expression of NOS2 (NOS2-/-), FGF-2 did not attenuate ischemia-induced LV dysfunction. Measurements of NO release demonstrated that FGF-2 perfusion significantly increased NO in wild-type but not in NOS2-/- hearts. We conclude that basic FGF attenuates myocardial stunning independent of alterations in [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] by stimulating NO production via an NOS2-dependent pathway. ischemia; nitric oxide; intracellular calcium; myocardial function