Nitric oxide is an important determinant of coronary flow in the isolated blood perfused rat heart.

Many vasoactive substances are involved in the regulation of vasomotor tone and some of them, like nitric oxide (NO), are derived from the endothelium. Nitric oxide is able to relax preconstricted coronary resistance vessels almost completely. However, it is not clear what the contribution of NO is to vasomotor tone in the intact blood perfused heart. The aim of the present study was to evaluate the contribution of NO to coronary pressure-flow relations. We used isovolumically beating, donor supported, blood perfused isolated rat hearts. We measured pressure-flow relations under control conditions, after blocking endothelial NO production with NG-nitro-L-Arginine (LNNA) and after administration of L-Arginine (L-Arg) in order to overrule the blocking effect. Administration of LNNA at a perfusion pressure of 105 mm Hg resulted, after about 40 min, in a significant (Wilcoxon's signed-rank test, (n = 8) p < 0.05) reduction of coronary flow to 47 +/- 5% (mean +/- SEM) of control and a reduction of developed isovolumic left-ventricular pressure to 62 +/- 4% of control. L-Arg returned flow to 60 +/- 7% of control which is a significant increase with respect to LNNA (p < 0.05). L-Arg did not increase the left-ventricular pressure. The entire perfusion pressure-flow relation (pressure range 65-125 mm Hg) was significantly shifted downwards after LNNA with respect to control. Pressure-flow relations after L-Arg were in between those during control and after block of NO production. L-Arg alone was found to have no effect on flow and left-ventricular pressure (n = 2) and both LNNA and L-Arg were found to have no effect on contractility of isolated trabeculae (n = 6), thus, coronary blood flow reduction after LNNA administration is mainly the result of inhibition of endothelial NO production. At a perfusion pressure of 105 mm Hg reactive hyperemia is still present after LNNA and subsequent L-Arg administration, indicating that endothelial NO is not the only factor involved in flow regulation. We conclude that endothelium-derived NO is involved in the control of coronary flow in the blood perfused rat heart.