Functional Role of Sodium-Calcium Exchange in the Regulation of Renal Vascular Resistance

Am J Physiol Renal Physiol. 2001 Jan;280(1):F155-61. doi: 10.1152/ajprenal.2001.280.1.F155.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiloride / analogs & derivatives*
  • Amiloride / pharmacology
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / physiology
  • Egtazic Acid / pharmacology
  • In Vitro Techniques
  • Kidney / blood supply
  • Kidney / physiology*
  • Kinetics
  • Male
  • Nickel / pharmacology
  • Niflumic Acid / pharmacology
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation / drug effects
  • Renal Circulation / physiology*
  • Sodium / physiology
  • Sodium-Calcium Exchanger / antagonists & inhibitors
  • Sodium-Calcium Exchanger / physiology*
  • Thiourea / analogs & derivatives*
  • Thiourea / pharmacology
  • Vascular Resistance / drug effects
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology

Substances

  • 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Sodium-Calcium Exchanger
  • benzamil
  • Niflumic Acid
  • Egtazic Acid
  • Amiloride
  • Nickel
  • Sodium
  • Thiourea