Nifedipine inhibits sphinogosine-1-phosphate-induced renovascular contraction in vitro and in vivo.
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 microM) 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 microg/kg) dose-dependently lowered renal blood flow from basal values of approximately 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 microg/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.
Bischoff
A
A
Medizinische Klinik, Universitätsklinikum Essen, Germany.
Finger
J
J
Michel
M C
MC
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008246:Lysophospholipids; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D020746:Calcium Channels, L-Type; D008246:Lysophospholipids; D014665:Vasodilator Agents; C060506:sphingosine 1-phosphate; D009543:Nifedipine; D013110:Sphingosine