Combination therapy with cerivastatin and nifedipine improves endothelial dysfunction after balloon injury in porcine coronary arteries

Yasuhiro Eto, Hiroaki Shimokawa, Yoshihiro Fukumoto, Yasuharu Matsumoto, Kunio Morishige, Ikuko Kunihiro, Tadashi Kandabashi, Akira Takeshita

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

HMG-CoA reductase inhibitors and calcium channel blockers have antiatherogenic effects; however, their mechanisms remain to be elucidated. This study examined the effect of cerivastatin and/or nifedipine on the endothelial dysfunction in porcine balloon-injured coronary arteries. Normal male pigs were randomly divided into the following four groups: control, cerivastatin (1 mg/kg/d PO), nifedipine (4 mg/kg/d PO), and their combination (n = 10 each). We started the treatments 3 days before balloon injury in the proximal left coronary arteries and continued for 4 weeks after the procedure. Then, we examined endothelial vasodilator functions ex vivo in organ chambers and in vitro by Western blotting for eNOS expression. Endothelium-dependent relaxations to serotonin, but not those to bradykinin or the calcium ionophore A23187 or endothelium-independent relaxations to sodium nitroprusside, were significantly impaired by balloon injury. The monotherapy with cerivastatin or nifedipine partially improved, and their combination supernormalized the relaxations to serotonin without affecting those to bradykinin or A23187 or endothelium-independent relaxations to sodium nitroprusside. The expression of eNOS was significantly reduced by balloon injury and normalized by the combination therapy. These results indicate that the combination therapy improves endothelial dysfunction after balloon injury, in which the up-regulation of eNOS may be involved.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume46
Issue number1
DOIs
Publication statusPublished - 2005 Jul 14
Externally publishedYes

Keywords

  • Balloon injury
  • Calcium channel blockers
  • Endothelium-dependent relaxation
  • Statin

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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