Sphingosine-1-phosphate reduces rat renal and mesenteric blood flow in vivo in a pertussis toxin-sensitive manner

1 Sphingolipids such as sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine constrict isolated rat intrarenal and mesenteric microvessels in vitro. The present study investigates their effects on the cardiovascular system in vivo in anaesthetized rats. 2 The animals were given intravenous or intrarenal arterial bolus injections of sphingolipids (0.1-100 mu g kg(-1)) with subsequent measurements of mean arterial pressure, heart rate and renal and mesenteric blood flows (RBF, MBF) using a pressure transducer and electromagnetic Row probes, respectively. 3 Intravenous injection of SPP rapidly (within 30 s), transiently and dose-dependently reduced RBF (maximally -4.0+/-0.3 ml min(-1)) and MBF (maximally -1.4+/-0.2 ml min(-1)), without affecting mean arterial pressure or heart rate. Other sphingolipids had no significant effect. 4 Intrarenal arterial SPP administration caused greater blood flow reductions (maximally -6.4+/-0.3 mi min(-1)) than systemic administration. Upon intrarenal administration, sphingosylphosphorylcholine also lowered RBF (maximally -2.8+/-0.6 ml min(-1)), while the other sphingolipids remained without effect. 5 Pretreatment with pertussis toxin (PTX, 10 mu g kg(-1)) 3 days before the acute experiment abolished the SPP-induced reductions of RBF and MBF. 6 These data demonstrate, that SPP is a potent vasoconstrictor in vivo, particularly in the renal vasculature, while the other structurally related sphingolipids had little if any effects. The PTX-sensitivity strongly suggests that the effects of SPP on renal and mesenteric blood flow are mediated by receptors coupled to G(i)-type G-proteins.