title: A calcium channel blocker amlodipine increases coronary blood flow via both adenosine- and NO-dependent mechanisms in ischemic hearts.
abstract: Amlodipine reduces oxidative stress that decreases NO and adenosine release. This study was undertaken to examine whether amlodipine mediates coronary vasodilation and improves myocardial metabolism and contractility in ischemic hearts via either adenosine- or NO-dependent mechanisms. In open-chest dogs, amlodipine (2 mug kg per min) was infused at the minimum dose that caused maximal coronary vasodilation. The perfusion pressure was reduced in the left anterior descending coronary artery so that coronary blood flow (CBF) decreased by 50%. Amlodipine increased the difference of the adenosine level (VAD (Ado): 119+/-14 to 281+/-46 nM) and the nitrate+nitrite level (VAD (NOx): 7.8+/-1.3 to 16.1+/-1.1 muM) between coronary venous and coronary arterial blood, and also increased CBF (50+/-3 to 69+/-6 ml/100 g/min). These changes were partially reversed by either 8-sulfophenyeltheophylline (8SPT) or l(omega)-nitro arginine methyl ester (l-NAME), and were completely blocked by both 8SPT and l-NAME. The reduction of CBF increased VAD (8-iso-prostaglandin F(2alpha)), and this increase was reduced by amlodipine (10.8+/-1.1 to 5.0+/-0.5 pg/ml). In addition, pretreatment with superoxide dismutase mimicked the coronary effects of amlodipine and blunted the response to amlodipine administration. Amlodipine-induced coronary vasodilation via both adenosine- and NO-dependent mechanisms. Adenosine and NO may interact in ischemic hearts to mediate coronary vasodilation by amlodipine.
authors.affiliation: Cardiovascular Division, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita City, Osaka Prefecture 565-8565, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ogita
authors.forename: Jiyoong
authors.initials: J
authors.lastname: Kim
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujita
authors.forename: Akio
authors.initials: A
authors.lastname: Hirata
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsukamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Ogai
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D017311:Amlodipine; D009569:Nitric Oxide; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D013482:Superoxide Dismutase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester