A calcium channel blocker amlodipine increases coronary blood flow via both adenosine- and NO-dependent mechanisms in ischemic hearts.
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.
Asanuma
Hiroshi
H
Cardiovascular Division, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita City, Osaka Prefecture 565-8565, Japan.
Minamino
Tetsuo
T
Sanada
Shoji
S
Ogita
Hisakazu
H
Kim
Jiyoong
J
Fujita
Masashi
M
Hirata
Akio
A
Tsukamoto
Osamu
O
Ogai
Akiko
A
Node
Koichi
K
Hori
Masatsugu
M
Tomoike
Hitonobu
H
Kitakaze
Masafumi
M
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*
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