Hina K, Watanabe H, Ueeda M, Yamada N, Saito D, Haraoka S, Tsuji T, Kusachi S
First Department of Internal Medicine, Okayama University Medical School, Japan.
Cardiovasc Res. 1989 Feb;23(2):104-11. doi: 10.1093/cvr/23.2.104.
Forskolin, a diterpene, directly stimulates adenylate cyclase and also potentiates receptor mediated stimulation of this enzyme by many stimulatory agonists. We exploited the potentiating effect of forskolin to test the hypothesis that activation of adenylate cyclase contributes to myocardial reactive hyperaemia, especially by release of adenosine at the time of brief coronary occlusions. In 10 open chest dogs, intracoronary forskolin infusions which produced plasma concentrations between 0.22 and 0.34 mumol.litre-1 slightly increased coronary blood flow and had no effect on haemodynamics or myocardial metabolism. Under these conditions, though peak reactive hyperaemic flow rates were not affected, forskolin infusions reversibly potentiated repayments of flow debt by 28, 25 and 27% following coronary occlusions of 15 s, 20 s and 30 s, respectively (p less than 0.05). In another seven dogs, after observations of the effects of forskolin (0.16-0.26 mumol), 10 mumol of 8-phenyltheophylline, a potent adenosine antagonist, was infused simultaneously with forskolin into the coronary arteries. Forskolin increased debt repayments by about 23-27% following 15 s, 20 s and 30 s occlusions, but with simultaneous 8-phenyltheophylline, forskolin induced increments in the debt repayments were reduced significantly (p less than 0.05). These results indicate that adenylate cyclase contributes to myocardial reactive hyperaemia, and adenosine has a significant role as metabolic regulator of reactive hyperaemia through activation of adenylate cyclase.
毛喉素，一种二萜类化合物，可直接刺激腺苷酸环化酶，并且还能增强许多刺激性激动剂对该酶的受体介导刺激作用。我们利用毛喉素的增强作用来检验以下假设：腺苷酸环化酶的激活有助于心肌反应性充血，特别是在短暂冠状动脉闭塞时通过腺苷的释放来实现。在10只开胸犬中，冠状动脉内注入毛喉素使血浆浓度达到0.22至0.34 μmol·L⁻¹，这略微增加了冠状动脉血流量，且对血流动力学或心肌代谢没有影响。在这些条件下，尽管反应性充血的峰值流速未受影响，但在分别进行15秒、20秒和30秒的冠状动脉闭塞后，注入毛喉素可使血流亏欠的偿还分别可逆性增强28%、25%和27%（p<0.05）。在另外7只犬中，在观察了毛喉素（0.16 - 0.26 μmol）的作用后，将10 μmol的8 - 苯基茶碱（一种有效的腺苷拮抗剂）与毛喉素同时注入冠状动脉。在15秒、20秒和30秒闭塞后，毛喉素使血流亏欠的偿还增加约23% - 27%，但同时使用8 - 苯基茶碱时，毛喉素诱导的血流亏欠偿还增加显著减少（p<0.05）。这些结果表明，腺苷酸环化酶有助于心肌反应性充血，并且腺苷通过激活腺苷酸环化酶作为反应性充血的代谢调节因子发挥重要作用。
