Role of the coronary endothelium in the regulation of sympathetic transmitter release in isolated rabbit hearts

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Abstract
The role of endothelium-derived relaxing factor (EDRF) and endothelin in the regulation of vascular tone are intensely studied at present. Since factors which directly affect vascular tone also frequently modulate sympathetic transmitter release, we found it of interest to study whether EDRF or endothelin displays such modulatory activity as well. Isolated rabbit hearts were perfused according to Langendorff, and the release of transmitter induced by sympathetic nerve stimulation was estimated by analysis of the effluent content of noradrenaline (NA) with liquid chromatography. The activity of EDRF spontaneously formed in the heart was counteracted by addition of haemoglobin (Hb, 2.4-15 g l-1) or facilitated by addition of superoxide dismutase (SOD, 14-140 U ml-1), to the perfusion solution. In other experiments authentic endothelin (0.1-10 nM) was given to the heart. Nerve stimulation (5 Hz for 30 s) elicited a release of NA into the cardiac effluent amounting to 319 .+-. 28 pmol (n=53). Hb lowered the coronary flow to 68 .+-. 9% (P < 0.01) and impaired the outflow of NA to 62 .+-. 9% of control (P < 0.01). SOD facilitated coronary flow by 11 .+-. 4% (P < 0.005), and augmented the outflow of NA by 15 .+-. 6% (P < 0.05). Endothelin dose-dependently inhibited the coronary flow, with an IC50 of about 1 nM, and in parallel decreased the efflux of NA. Mechanical obstruction of the coronary flow induced an attenuation of the efflux of NA that was quantitatively similar to the flow reduction. The data indicate that the efflux of NA from this rabbit heart hpereparation is closely dependent on the coronary flow rate. EDRF and endothelin seem to affect the efflux of NA by changing coronary flow, but not by direct interference with the process of sympathetic transmitter release.