Ca2+ channel subtypes and pharmacology in the kidney

Koichi Hayashi, Shu Wakino, Naoki Sugano, Yuri Ozawa, Koichiro Homma, Takao Saruta

Research output: Contribution to journalReview article

184 Citations (Scopus)

Abstract

A large body of evidence has accrued indicating that voltage-gated Ca channel subtypes, including L-, T-, N-, and P/Q-type, are present within renal vascular and tubular tissues, and the blockade of these Ca channels produces diverse actions on renal microcirculation. Because nifedipine acts exclusively on L-type Ca channels, the observation that nifedipine predominantly dilates afferent arterioles implicates intrarenal heterogeneity in the distribution of L-type Ca channels and suggests that it potentially causes glomerular hypertension. In contrast, recently developed Ca channel blockers (CCBs), including mibefradil and efonidipine, exert blocking action on L-type and T-type Ca channels and elicit vasodilation of afferent and efferent arterioles, which suggests the presence of T-type Ca 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 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 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 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 channels may offer additive benefits through nonhemodynamic mechanisms in the progression of chronic kidney disease.

Original languageEnglish
Pages (from-to)342-353
Number of pages12
JournalCirculation research
Volume100
Issue number3
DOIs
Publication statusPublished - 2007 Feb 1

Keywords

  • Afferent arteriole
  • Ca channel blockers
  • Efferent arteriole
  • Efonidipine
  • Mibefradil
  • Renal disease
  • Renal microcirculation
  • Voltage-dependent Ca channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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