title: Celiprolol increases coronary blood flow and reduces severity of myocardial ischemia via nitric oxide release.
abstract: Celiprolol is a selective beta(1)-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 L omega-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 beta(2)-adrenoceptor antagonist, did not blunt the effects of celiprolol and a nonselective beta-adrenoceptor antagonist, propranolol, increased neither CBF nor cardiac NO release, indicating that the effect of celiprolol is independent of beta-adrenoceptor blockade. It was concluded that celiprolol mediates coronary vasodilation and improves myocardial ischemia through NO-dependent mechanisms.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ueda
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sakata
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Jiyoong
authors.initials: J
authors.lastname: Kim
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ogita
authors.forename: Michihiko
authors.initials: M
authors.lastname: Tada
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000818:Animals; D017272:Celiprolol / Q000494:pharmacology* / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D017272:Celiprolol