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

研究成果: Article査読

9 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)942-948
ページ数7
ジャーナルJournal of Cardiovascular Pharmacology
35
6
DOI
出版ステータスPublished - 2000 6月 13

ASJC Scopus subject areas

  • 薬理学
  • 循環器および心血管医学

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