Pathophysiological significance of T-type Ca2+ channels: Role of T-type Ca2+ channels in renal microcirculation

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

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Since conventional Ca2+ antagonists, with predominant blockade of L-type voltage-dependent Ca2+ channels, elicit preferential dilation of afferent arterioles, they might ostensibly aggravate glomerular hypertension. Recently, novel Ca2+ antagonists, with inhibitory action on L-/T-type Ca2+ channels, have been reported to dilate both afferent and efferent arterioles. The present review attempted to characterize the renal action of these Ca2+ antagonists and evaluated the consequences following the treatment with these agents. In contrast to conventional Ca2+ antagonists (e.g., nifedipine), novel antagonists (e.g., benidipine, efonidipine) potently dilated afferent and efferent arterioles; their action on efferent arterioles appeared to be mediated by the T-type Ca2+ channel blockade, probably through the inhibition of the intracellular Ca2+ release. The comparison of the anti-proteinuric action in subtotally nephrectomized rats showed that efonidipine exerted more prominent action than nifedipine. Furthermore, Ca2+ antagonists with T-type Ca2+ inhibitory action inhibited renin/aldosterone release and proinflammatory process. Finally, patients with chronic renal disease given a 48-week efonidipine treatment showed reduced proteinuria, and this effect was seen even when mean arterial blood pressure failed to become less than 100 mmHg. Collectively, T-type Ca2+ channel blockade provides beneficial action in renal injury. Various mechanisms serve to protect against renal injury, including systemic/glomerular hemodynamic action and non-hemodynamic mechanisms.

Original languageEnglish
Pages (from-to)221-227
Number of pages7
JournalJournal of Pharmacological Sciences
Volume99
Issue number3
DOIs
Publication statusPublished - 2005 Dec 5

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Keywords

  • Efonidipine
  • Mibefradil
  • Renal disease
  • Renal microcirculation
  • Voltage-dependent Ca channel

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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