Characterization of Endothelin Receptors in Isolated, Perfused Human Spleen

At present, there is no information on endothelin-1 (ET-1)-mediated vascular effects in the human spleen. The objectives of this study were to investigate the in vitro vascular responses to ET-1 using pharmacologic probes (selective ET receptor agonists/antagonists) and to characterize the ET receptor population in the human spleen. Spleens (n= 6) were removed from patients for treatment of underlying disease. The organs were perfused with warmed (37°C), oxygenated (95% O2/5% CO2) Krebs solution at constant flow, with continuous recording of splenic arterial perfusion pressure(SAPP). The increases in SAPP caused by injection of ET-1 (ETA/ETB agonist) were markedly reduced in the presence of the selective ETA antagonist FR-139317, whereas those induced by IRL-1620 (an ETB agonist) and norepinephrine(NE) were unchanged. The increases in SAPP induced by intra-arterial bolus injections of NE and ET-1 were significantly (p < 0.05) potentiated by indomethacin[INDO; a cyclo-oxygenase (COX) inhibitor] alone and the responses to both peptides (ET-1 and IRL-1620) were significantly (p < 0.05) potentiated by INDO and L-NAME [a nitric oxide (NO) synthase inhibitor] together. We conclude that ET-1 contributes to the regulation of vascular tone in human spleen through activation of both ETA and ETB receptors and that these responses are modulated by concomitant release of prostaglandins and NO.