Functional and pharmacological consequences of the distribution of voltage-gated calcium channels in the renal blood vessels

Acta Physiol (Oxf). 2013 Apr;207(4):690-9. doi: 10.1111/apha.12070. Epub 2013 Feb 21.

Abstract

Calcium channel blockers are widely used to treat hypertension because they inhibit voltage-gated calcium channels that mediate transmembrane calcium influx in, for example, vascular smooth muscle and cardiomyocytes. The calcium channel family consists of several subfamilies, of which the L-type is usually associated with vascular contractility. However, the L-, T- and P-/Q-types of calcium channels are present in the renal vasculature and are differentially involved in controlling vascular contractility, thereby contributing to regulation of kidney function and blood pressure. In the preglomerular vascular bed, all the three channel families are present. However, the T-type channel is the only channel in cortical efferent arterioles which is in contrast to the juxtamedullary efferent arteriole, and that leads to diverse functional effects of L- and T-type channel inhibition. Furthermore, by different mechanisms, T-type channels may contribute to both constriction and dilation of the arterioles. Finally, P-/Q-type channels are involved in the regulation of human intrarenal arterial contractility. The calcium blockers used in the clinic affect not only L-type but also P-/Q- and T-type channels. Therefore, the distinct effect obtained by inhibiting a given subtype or set of channels under experimental settings should be considered when choosing a calcium blocker for treatment. T-type channels seem to be crucial for regulating the GFR and the filtration fraction. Use of blockers is expected to lead to preferential efferent vasodilation, reduction of glomerular pressure and proteinuria. Therefore, renovascular T-type channels might provide novel therapeutic targets, and may have superior renoprotective effects compared to conventional calcium blockers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channels / drug effects*
  • Calcium Channels / physiology*
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / physiology
  • Calcium Channels, T-Type / drug effects
  • Calcium Channels, T-Type / physiology
  • Disease Models, Animal
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / physiology
  • Humans
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Mice
  • Rats
  • Renal Artery / drug effects
  • Renal Artery / physiology*
  • Renal Artery / physiopathology

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium Channels, T-Type