Role of actions of calcium antagonists on efferent arterioles - With special references to glomerular hypertension

Koichi Hayashi, Yuri Ozawa, Keiji Fujiwara, Shu Wakino, Hiroo Kumagai, Takao Saruta

Research output: Contribution to journalReview article

91 Citations (Scopus)

Abstract

Although calcium antagonists are used as a first-line antihypertensive agent, controversy attends the renal microvascular effects of calcium antagonists. Since calcium antagonists elicit predominant vasodilation of the afferent arteriole, they might ostensibly aggravate glomerular hypertension. Recently, novel types of calcium antagonists have been developed, some of which are reported to dilate efferent as well as afferent arterioles. The present review attempted to characterize the renal microvascular action of calcium antagonists, and evaluated the consequences of renal injury following the treatment with these antagonists. In contrast to predominant afferent arteriolar action of conventional calcium antagonists (e.g. nifedipine, nicardipine, amlodipine and diltiazem), novel antagonists (e.g. manidipine, nilvadipine, benidipine and efonidipine) potently dilated both afferent and efferent arterioles. The vasodilator action on efferent arterioles appears to be mediated in part by the blockade of T-type calcium channels, particularly through the inhibition of the intracellular calcium release mechanism. The comparison of the anti-proteinuric action of calcium antagonists in subtotally nephrectomized rats showed that efonidipine and enalapril, both possessing vasodilator action on efferent arterioles, exerted more prominent action than other calcium antagonists. Finally, in patients with chronic renal disease, a 48-week treatment with efonidipine reduced proteinuria, and this effect was seen even when the mean arterial blood pressure failed to reach below 100 mm Hg. In conclusion, although calcium antagonists potently inhibit afferent arteriolar constriction, efferent arteriolar responses to these agents vary, depending on the types of calcium antagonists used. These divergent actions of these agents on the efferent arteriole may alter differently the glomerular hemodynamics, and could affect the final outcome of underlying renal diseases.

Original languageEnglish
Pages (from-to)229-244
Number of pages16
JournalAmerican Journal of Nephrology
Volume23
Issue number4
DOIs
Publication statusPublished - 2003 Aug 22

Keywords

  • Afferent arteriole
  • Calcium antagonists
  • Efferent arteriole
  • Efonidipine
  • Hypertension
  • Mibefradil
  • Renal disease
  • Renal microcirculation
  • Voltage-dependent calcium channels

ASJC Scopus subject areas

  • Nephrology

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