T-type Ca channel blockade as a determinant of kidney protection

Koichi Hayashi, Koichiro Homma, Shu Wakino, Hirobumi Tokuyama, Naoki Sugano, Takao Saruta, Hiroshi Itoh

Research output: Contribution to journalReview article

34 Citations (Scopus)

Abstract

Voltage-dependent Ca channels are classified into several subtypes based on the isoform of their α1 subunits. Traditional Ca channels blockers (CCBs), including nifedipine and amlodip-ine, act predominantly on L-type Ca channels, whereas novel CCBs such as efonidipine, beni-dipine and azelnidipine inhibit both L-type and T-type Ca channels. Furthermore, cilnidipine blocks L-type and N-type Ca channels. These CCBs exert divergent actions on renal microves-sels. L-type CCBs preferentially dilate afferent arterioles, whereas both L-/T-type and L-/N-type CCBs potently dilate afferent and efferent arterioles. The distinct actions of CCBs on the renal microcirculation are reflected by changes in glomerular capillary pressure and subsequent renal injury: L-type CCBs favor an increase in glomerular capillary pressure, whereas L-/T-type and L-/N-type CCBs alleviate glomerular hypertension. The renal protective action of L-/T-type CCBs is also mediated by non-hemodynamic mechanisms, i.e., inhibition of the inflammatory process and inhibition of Rho kinase and aldosterone secretion. Finally, a growing body of evidence indicates that T-type CCBs offer more beneficial action on proteinuria and renal survival rate than L-type CCBs in patients with chronic kidney disease (CKD). Similarly, in CKD patients treated with renin-angiotensin blockers, add-on therapy with N-type CCBs is more potent in reducing proteinuria than that with L-type CCBs, although no difference is found in the subgroup with diabetic nephropathy. Thus, the strategy for hypertension treatment with CCBs has entered a new era: treatment selection depends not only on blood pressure control but also on the subtypes of CCBs.

Original languageEnglish
Pages (from-to)84-95
Number of pages12
JournalKeio Journal of Medicine
Volume59
Issue number3
DOIs
Publication statusPublished - 2010 Sep

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Keywords

  • Chronic kidney disease
  • Efonidipine
  • Renal microcirculation
  • T-type calcium channels
  • Voltage-dependent Ca channels

ASJC Scopus subject areas

  • Medicine(all)

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