title: Functional role of sodium-calcium exchange in the regulation of renal vascular resistance.
abstract: Our study aimed to assess a possible functional role of the Na(+)/Ca(2+) exchanger in the regulation of renal vascular resistance (RVR). Therefore, we investigated the effects of an inhibition of the Na(+)/Ca(2+) exchanger either by lowering the extracellular sodium concentration ([Na(+)](e)) or, pharmacologically on RVR, by using isolated perfused rat kidneys. Graded decreases in [Na(+)](e) led to dose-dependent increases in RVR to 4.3-fold (35 mM Na(+)). This vasoconstriction was markedly attenuated by lowering the extracellular calcium concentration, by the L-type calcium channel blocker amlodipine or by the chloride channel blocker niflumic acid. Further lowering of [Na(+)](e) to 7 mM led to an increase in RVR to 7.5-fold. In this setting, amlodipine did not influence the magnitude but did influence the velocity of vasoconstriction. Pharmacological blockade of the Na(+)/Ca(2+) exchanger with KB-R7943, benzamil, or nickel resulted in significant vasoconstriction (RVR 2.5-, 1.8-, and 4.2-fold of control, respectively). Our data suggest a functional role of the Na(+)/Ca(2+) exchanger in the renal vascular bed. In conditions of partial replacement of [Na(+)](e), vasoconstriction is dependent on chloride and L-type calcium channels. A total replacement of [Na(+)](e) leads to a vasoconstriction that is nearly independent of L-type calcium channels. This might be due to an active calcium transport into the cell by the Na(+)/Ca(2+) exchanger.
authors.affiliation: Institut für Physiologie I, Universität Regensburg, D-93040 Regensburg, Germany. frank.schweda@klinik.uni-regensburg.de
authors.forename: F
authors.initials: F
authors.lastname: Schweda
authors.forename: H
authors.initials: H
authors.lastname: Seebauer
authors.forename: B K
authors.initials: BK
authors.lastname: Krämer
authors.forename: A
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009532:Nickel / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; C013407:benzamil; D009544:Niflumic Acid; D004533:Egtazic Acid; D000584:Amiloride; D009532:Nickel; D012964:Sodium; D013890:Thiourea