Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10954326 | Journal of Molecular and Cellular Cardiology | 2005 | 10 Pages |
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 μg 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 μM) 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 lÏ-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 F2α), 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.
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Authors
Hiroshi Asanuma, Tetsuo Minamino, Shoji Sanada, Hisakazu Ogita, Jiyoong Kim, Masashi Fujita, Akio Hirata, Osamu Tsukamoto, Akiko Ogai, Koichi Node, Masatsugu Hori, Hitonobu Tomoike, Masafumi Kitakaze,