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

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. The animals were given intravenous or intrarenal arterial bolus injections of sphingolipids (0.1–100 μg 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 flow probes, respectively. 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. Intrarenal arterial SPP administration caused greater blood flow reductions (maximally −6.4±0.3 ml min−1) than systemic administration. Upon intrarenal administration, sphingosylphos‐ phorylcholine also lowered RBF (maximally −2.8±0.6 ml min−1), while the other sphingolipids remained without effect. Pretreatment with pertussis toxin (PTX, 10 μg kg−1) 3 days before the acute experiment abolished the SPP‐induced reductions of RBF and MBF. 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 Gi‐type G‐proteins. British Journal of Pharmacology (2000) 130, 1878–1883; doi:10.1038/sj.bjp.0703516