Celiprolol increases coronary blood flow and reduces severity of myocardial ischemia via nitric oxide release

Hiroshi Asanuma, Koichi Node, Tetsuo Minamino, Shoji Sanada, Seiji Takashima, Yasunori Ueda, Yasuhiko Sakata, Masanori Asakura, Jiyoong Kim, Hisakazu Ogita, Michihiko Tada, Masatsugu Hori, Masafumi Kitakaze

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Celiprolol is a selective β1-adrenoceptor antagonist with antihypertensive actions, which causes renal vasodilation by increasing tissue nitric oxide (NO) levels. The authors tested whether celiprolol increases coronary blood flow (CBF) by increasing cardiac NO release in the ischemic heart in vivo. In open-chest dogs, coronary perfusion pressure of the left anterior descending coronary artery was reduced so that CBF decreased to 60% of control levels, and thereafter, coronary perfusion pressure was maintained constant. Ten minutes after the reduction of coronary perfusion pressure, we infused celiprolol into the left anterior descending coronary artery and measured fractional shortening and lactate extraction ratio as indices of regional myocardial contractility and metabolism. CBF significantly increased from 51.5 mL/100 g/min ± 1.9 to 67.0 mL/100 g/min ± 5.1 20 minutes after celiprolol infusion without changes in coronary perfusion pressure, while fractional shortening and lactate extraction ratio increased. Celiprolol also increased cardiac NO release. The Lω-nitroarginine methyl ester, the inhibitor of NO synthase, attenuated the increases in CBF, fractional shortening, lactate extraction ratio, and cardiac NO release due to celiprolol. ICI 118551, a β2-adrenoceptor antagonist, did not blunt the effects of celiprolol and a nonselective β-adrenoceptor antagonist, propranolol, increased neither CBF nor cardiac NO release, indicating that the effect of celiprolol is independent of β-adrenoceptor blockade. It was concluded that celiprolol mediates coronary vasodilation and improves myocardial ischemia through NOdependent mechanisms.

Original languageEnglish
Pages (from-to)499-505
Number of pages7
JournalJournal of cardiovascular pharmacology
Volume41
Issue number4
DOIs
Publication statusPublished - 2003 Apr 1
Externally publishedYes

Keywords

  • Coronary blood flow
  • Fractional shortening
  • Ischemia
  • Nitric oxide
  • β-adrenoceptor

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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