Nifedipine inhibits sphingosine-1-phosphate-induced renovascular contraction in vitro and in vivo
2001
Sphingosine-1-phosphate (SPP) can constrict isolated intrarenal blood vessels in vitro and reduce renal blood flow in vivo. The present study has investigated the role of extracellular Ca2+ and dihydropyridine-sensitive Ca2+ channels in SPP-induced renovascular contraction. In isolated intrarenal microvessels, cumulative addition of SPP (0.1–100 µM) caused concentration-dependent vasoconstriction (maximum effect 5.0±1.1 mN). In the presence of nifedipine (300 nM, added 30 min before SPP) or EGTA (5 mM, added 1 min before SPP), SPP-induced vasoconstriction was almost completely abolished. In thiobutabarbitone-anaesthetized rats, i.v. bolus injections of SPP (1–100 µg/kg) dose-dependently lowered renal blood flow from basal values of ~4.8 ml/min by up to 2.2±0.2 ml/min but had only little effect on mean arterial pressure. Pretreatment with nifedipine (10–100 µg/kg per min, i.v.) dose-dependently attenuated SPP-induced renal blood flow reductions. We conclude that SPP-induced renovascular contraction requires the influx of extracellular Ca2+ which may occur largely via nifedipine-sensitive L-type Ca2+ channels.
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