Ca2+ channel subtypes and pharmacology in the kidney

Circ Res. 2007 Feb 16;100(3):342-53. doi: 10.1161/01.RES.0000256155.31133.49.

Abstract

A large body of evidence has accrued indicating that voltage-gated Ca(2+) channel subtypes, including L-, T-, N-, and P/Q-type, are present within renal vascular and tubular tissues, and the blockade of these Ca(2+) channels produces diverse actions on renal microcirculation. Because nifedipine acts exclusively on L-type Ca(2+) channels, the observation that nifedipine predominantly dilates afferent arterioles implicates intrarenal heterogeneity in the distribution of L-type Ca(2+) channels and suggests that it potentially causes glomerular hypertension. In contrast, recently developed Ca(2+) channel blockers (CCBs), including mibefradil and efonidipine, exert blocking action on L-type and T-type Ca(2+) channels and elicit vasodilation of afferent and efferent arterioles, which suggests the presence of T-type Ca(2+) channels in both arterioles and the distinct impact on intraglomerular pressure. Recently, aldosterone has been established as an aggravating factor in kidney disease, and T-type Ca(2+) channels mediate aldosterone release as well as its effect on renal efferent arteriolar tone. Furthermore, T-type CCBs are reported to exert inhibitory action on inflammatory process and renin secretion. Similarly, N-type Ca(2+) channels are present in nerve terminals, and the inhibition of neurotransmitter release by N-type CCBs (eg, cilnidipine) elicits dilation of afferent and efferent arterioles and reduces glomerular pressure. Collectively, the kidney is endowed with a variety of Ca(2+) channel subtypes, and the inhibition of these channels by their specific CCBs leads to variable impact on renal microcirculation. Furthermore, multifaceted activity of CCBs on T- and N-type Ca(2+) channels may offer additive benefits through nonhemodynamic mechanisms in the progression of chronic kidney disease.

Publication types

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

MeSH terms

  • Aldosterone / physiology
  • Animals
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / classification
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Arterioles / drug effects
  • Arterioles / physiology
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channels / chemistry
  • Calcium Channels / classification
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Calcium Channels, L-Type / chemistry
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / physiology
  • Calcium Channels, N-Type / chemistry
  • Calcium Channels, N-Type / drug effects
  • Calcium Channels, N-Type / physiology
  • Calcium Channels, T-Type / chemistry
  • Calcium Channels, T-Type / drug effects
  • Calcium Channels, T-Type / physiology
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / physiopathology
  • Diabetes Mellitus / physiopathology
  • Disease Progression
  • Humans
  • Hydronephrosis / physiopathology
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / physiology
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Mice
  • Mice, Knockout
  • Microcirculation / drug effects
  • Microcirculation / physiology
  • Models, Biological
  • Neurotransmitter Agents / metabolism
  • Protein Subunits
  • Rats
  • Renal Circulation / drug effects
  • Renal Circulation / physiology
  • Renin / metabolism
  • Renin-Angiotensin System / physiology
  • Vasodilation / drug effects

Substances

  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Calcium Channels, T-Type
  • Neurotransmitter Agents
  • Protein Subunits
  • Aldosterone
  • Renin