This study examined whether NO is involved in the in-vivo coronary vasodilator effects of amlodipine (a calcium channel blocker) and whether heart failure (HF) alters the coronary responses to amlodipine. 2. Nine conscious dogs were chronically instrumented to measure circumflex coronary blood flow (CBF) and coronary diameter (CD). Drugs were administered directly into the circumflex artery through an indwelling catheter to avoid systemic changes. HF was induced by right ventricular pacing (240 b.p.m., 3 weeks). 3. Compared with control (C), in HF, coronary responses to acetylcholine (1 - 10 ng kg(-1)) were reduced while responses to nitroglycerin (0.1 - 0.5 microg kg(-1)) were unchanged. In C, amlodipine (30 - 150 microg kg(-1)), increased dose-dependently CBF and CD. After LNA (a NO synthase inhibitor, 2 mg kg(-1)), amlodipine produced less increases in CBF and CD (+121+/-26 ml min(-1) and +76+/-35 microm versus +196+/-40 ml min(-1) and +153+/-39 microm respectively for 150 microg kg(-1) amlodipine alone, both P<0.05). In HF, the coronary responses to amlodipine were reduced (150 microg kg(-1) of amlodipine increased CBF and CD +121+/-23 ml min(-1) and +77+/-21 microm respectively, both P<0.05). After LNA, the CBF responses to amlodipine tended to be reduced (+94+/-19 ml min(-1) at 150 microg kg(-1)) but CD responses were significantly reduced (+41+/-16 microm, P<0.05). The supplementation with L-arginine did not enhance the coronary responses to amlodipine. 4. These results indicate that, in conscious dogs, NO participates in the coronary responses to amlodipine and in HF, the coronary responses to amlodipine are reduced, which is related to a reduced NO production.
摘要
本研究探讨了一氧化氮（NO）是否参与氨氯地平（一种钙通道阻滞剂）的体内冠状动脉舒张作用，以及心力衰竭（HF）是否会改变冠状动脉对氨氯地平的反应。2. 对9只清醒犬进行长期仪器植入，以测量左旋冠状动脉血流量（CBF）和冠状动脉直径（CD）。通过留置导管将药物直接注入左旋动脉，以避免全身变化。通过右心室起搏（240次/分钟，持续3周）诱导心力衰竭。3. 与对照组（C）相比，在心力衰竭组中，冠状动脉对乙酰胆碱（1 - 10 ng kg(-1)）的反应降低，而对硝酸甘油（0.1 - 0.5 microg kg(-1)）的反应未改变。在对照组中，氨氯地平（30 - 150 microg kg(-1)）剂量依赖性地增加CBF和CD。在给予左旋硝基精氨酸甲酯（LNA，一种NO合酶抑制剂，2 mg kg(-1)）后，氨氯地平对CBF和CD的增加作用减弱（对于单独使用150 microg kg(-1)氨氯地平，CBF和CD分别增加+196±40 ml min(-1)和+153±39 microm，而给予LNA后分别增加+121±26 ml min(-1)和+76±35 microm，两者P<0.05）。在心力衰竭组中，冠状动脉对氨氯地平的反应降低（150 microg kg(-1)氨氯地平使CBF和CD分别增加+121±23 ml min(-1)和+77±21 microm，两者P<0.05）。给予LNA后，氨氯地平对CBF的反应趋于降低（150 microg kg(-1)时为+94±19 ml min(-1)），但对CD的反应显著降低（+41±16 microm，P<0.05）。补充L-精氨酸并未增强冠状动脉对氨氯地平的反应。4. 这些结果表明，在清醒犬中，NO参与冠状动脉对氨氯地平的反应，而在心力衰竭时，冠状动脉对氨氯地平的反应降低，这与NO生成减少有关。
