Calcium channel blocker nilvadipine, but not diltiazem, inhibits ocular inflammation in endotoxin-induced uveitis

Susumu Ishida, Takashi Koto, Norihiro Nagai, Yuichi Oike

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose: Calcium channel blockers (CCBs), widely used for hypertensive patients, have recently been shown to inhibit atherosclerosis by their antioxidative action. The aim of the present study was to examine whether the CCBs nilvadipine and diltiazem reduce ocular inflammation in endotoxin-induced uveitis (EIU). Methods: EIU was induced in male C57/B6 mice with a single intraperitoneal injection of lipopolysaccharide (LPS). The animals received intraperitoneal injections of either nilvadipine, diltiazem, or vehicle for 5 days before the LPS application. Twenty-four hours after EIU induction, adherent leukocytes to the retinal vasculature were counted with a concanavalin A lectin perfusion-labeling technique. The protein concentration in the aqueous humor was measured to assess blood-ocular barrier breakdown. Retinal levels of intercellular adhesion molecule (ICAM)-1 and monocyte chemotactic protein (MCP)-1 were analyzed by enzyme-linked immunosorbent assay. LPS-stimulated generation of superoxide in murine microvascular endothelial cells was examined with a nitroblue tetrazolium assay. Results: Compared to vehicle treatment, application of nilvadipine, but not diltiazem, led to significant suppression of EIU-associated retinal leukocyte adhesion, together with anterior-chamber protein leakage, retinal expression of ICAM-1 and MCP-1, and LPS-induced superoxide generation in vitro. Conclusions: The CCB nilvadipine exercises an inhibitory effect on the pathogenesis of ocular inflammation through the suppression of inflammation-related molecules.

Original languageEnglish
Pages (from-to)594-601
Number of pages8
JournalJapanese Journal of Ophthalmology
Volume54
Issue number6
DOIs
Publication statusPublished - 2010 Nov

Fingerprint

nilvadipine
Diltiazem
Uveitis
Calcium Channel Blockers
Endotoxins
Lipopolysaccharides
Inflammation
Chemokine CCL2
Intercellular Adhesion Molecule-1
Intraperitoneal Injections
Superoxides
Leukocytes
Nitroblue Tetrazolium
Aqueous Humor
Anterior Chamber
Concanavalin A
Lectins
Atherosclerosis
Proteins
Endothelial Cells

Keywords

  • calcium channel blocker
  • endotoxin-induced uveitis
  • intercellular adhesion

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Calcium channel blocker nilvadipine, but not diltiazem, inhibits ocular inflammation in endotoxin-induced uveitis. / Ishida, Susumu; Koto, Takashi; Nagai, Norihiro; Oike, Yuichi.

In: Japanese Journal of Ophthalmology, Vol. 54, No. 6, 11.2010, p. 594-601.

Research output: Contribution to journalArticle

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