Sakai K, Saito K, Akima M
Central Research Laboratories, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Eur J Pharmacol. 1998 Mar 5;344(2-3):153-9. doi: 10.1016/s0014-2999(97)01566-5.
The action of calcitonin gene-related peptide (CGRP) on the vasodepressor response to adenosine was investigated in anesthetized rats. I.v. bolus injections of adenosine (1-100 microg/kg), acetylcholine (0.05-0.4 microg/kg), isoproterenol (1-30 ng/kg), nitroglycerin (0.3-10 microg/kg) and diltiazem (10-300 microg/kg) produced dose-dependent decreases in blood pressure, accompanied by changes in heart rate. Only the vasodepressor response elicited by adenosine, among the agents tested, was significantly enhanced by i.v. infusion of either CGRP (1 ng/kg per min) or cromakalim (0.1 microg/kg per min), which possesses glibenclamide-sensitive K+ channel opening activity. After i.v. treatment with glibenclamide (20 mg/kg), the vasodepressor responses not only to adenosine but also to CGRP (0.5 microg/kg) and cromakalim (30 microg/kg) were significantly reduced, while those to acetylcholine and isoproterenol remained unchanged. The result indicates that the enhancement of the adenosine-induced vasodepression by CGRP, like that elicited by cromakalim, seems to be mediated at least partly through ATP-sensitive K+ channel activation.
在麻醉大鼠中研究了降钙素基因相关肽（CGRP）对腺苷血管减压反应的作用。静脉推注腺苷（1 - 100微克/千克）、乙酰胆碱（0.05 - 0.4微克/千克）、异丙肾上腺素（1 - 30纳克/千克）、硝酸甘油（0.3 - 10微克/千克）和地尔硫䓬（10 - 300微克/千克）可使血压呈剂量依赖性下降，并伴有心率变化。在所测试的药物中，只有腺苷引起的血管减压反应可被静脉输注CGRP（1纳克/千克每分钟）或具有格列本脲敏感钾通道开放活性的克罗卡林（0.1微克/千克每分钟）显著增强。静脉注射格列本脲（20毫克/千克）后，不仅对腺苷的血管减压反应，而且对CGRP（0.5微克/千克）和克罗卡林（30微克/千克）的血管减压反应均显著降低，而对乙酰胆碱和异丙肾上腺素的反应保持不变。结果表明，CGRP对腺苷诱导的血管舒张的增强作用，与克罗卡林引起的作用一样，似乎至少部分是通过ATP敏感性钾通道激活介导的。
