Distinct action of aranidipine and its active metabolite on renal arterioles, with special reference to renal protection

Akira Nakamura, Koichi Hayashi, Keiji Fujiwara, Yuri Ozawa, Masanori Honda, Takao Saruta

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Aranidipine, a newly developed calcium antagonist, possesses unique pharmacologic characteristics in that its metabolite (M-1) still has antihypertensive action. We examined the effects of both agents on renal microcirculation using the isolated perfused hydronephrotic rat kidney. During norepinephrine-induced constriction, the addition of aranidipine dilated both afferent and efferent arterioles in a dose-dependent manner; at 10-6 M, 83 ± 6% and 90 ± 6% reversal, respectively. In contrast, its active metabolite exerted dilator action predominantly on the afferent arteriole (79 ± 4% vs. 44 ± 17% at 10-6 M for afferent and efferent arterioles, respectively). We further examined the long-term (8 weeks) effect of these agents on the development of renal injury in salt-loaded subtotally nephrectomized spontaneously hypertensive rats. Both aranidipine and M-1 reduced blood pressure by a similar magnitude. The decreases in proteinuria were observed in the aranidipine-treated group at weeks 6, 8, and 10, whereas in the M-1 group, significant reduction was attained only at week 6. Histopathologic examination revealed that both treatments improved glomerular and arteriolar sclerosis. Glomerular sclerosis, however, was less pronounced in the aranidipine-treated group than in the M-1 group. In conclusion, aranidipine has dilator action on both arterioles, whereas M-1 caused predominant dilation of afferent arterioles. Such metabolic changes may constitute a determinant of efferent arteriolar action of the calcium antagonist.

Original languageEnglish
Pages (from-to)942-948
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume35
Issue number6
DOIs
Publication statusPublished - 2000 Jun 13

Keywords

  • Afferent arterioles
  • Aranidipine
  • Calcium antagonists
  • Efferent arterioles
  • Proteinuria
  • Renal injury

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Distinct action of aranidipine and its active metabolite on renal arterioles, with special reference to renal protection'. Together they form a unique fingerprint.

  • Cite this