Release of endothelial mediators and sympathetic transmitters at different coronary flow rates in rabbit hearts.

摘要

1. The release of three endothelial mediators, namely, endothelial-derived relaxing factor (EDRF), prostacyclin (PGI2) and endothelin, and of two sympathetic neurotransmitters, noradrenaline and neuropeptide Y (NPY), from resting or sympathetically stimulated rabbit Langendorff hearts was investigated at normal or elevated coronary flow. The sympathetic nerves to the hearts were stimulated at 5 Hz for 30 s and the cardiac effluent was analysed for nitrite (metabolite of EDRF) with electron paramagnetic resonance spectrometry, for 6-keto-PGF1 alpha (metabolite of PGI2) with gas chromatography/mass spectrometry, for endothelin- and NPY-like immunoreactivity with radioimmunoassay, and for noradrenaline and purines with liquid chromatography. 2. During perfusion of the hearts at normal flow (35 +/- 1.4 ml min-1) the effluent concentration of nitrite was 0.15 +/- 0.02 microM, that of 6-keto-PGF1 alpha 0.74 +/- 0.08 nM, and that of endothelin-like immunoreactivity 0.18 +/- 0.01 pM. Nerve stimulation augmented the release of 6-keto-PGF1 alpha from 76 +/- 8 to 99 +/- 10 pmol (3 min)-1 (P less than 0.05), but did not affect the release of nitrite or endothelin-like immunoreactivity. Nerve stimulation also facilitated the outflow of noradrenaline and of NPY-like immunoreactivity by 52 +/- 11 pmol (3 min)-1 and 19 +/- 7 fmol (3 min)-1, respectively. 3. Elevation of the coronary flow to 79 +/- 3.2 ml min-1 did not affect the effluent concentrations of nitrite, 6-keto-PGF1 alpha and endothelin-like immunoreactivity, implying that their outflows were augmented. Sympathetic stimulation at elevated coronary flow did not further augment the outflow of endothelial mediators or of NPY-like immunoreactivity, but increased the outflow of noradrenaline by 62 +/- 12%, in comparison to stimulation at normal flow. Perfusion of the heart with the noradrenaline uptake blocker desipramine (5 microM) completely abolished the promoting effecting of elevated coronary flow on noradrenaline outflow during sympathetic stimulation. 4. These data indicate that an increase in coronary flow in perfused rabbit hearts is paralleled by a corresponding facilitation of the formation of the endothelial mediators, EDRF, prostacyclin and endothelin. Such an elevation of mediator formation does not affect nerve stimulation-induced release of sympathetic transmitters in the heart.