Takashio T, Yamashita H, Onodera S, Inoue H, Oomiya H, Tanazawa S, Obara A, Imamoto T
First Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1990 Jun;28(6):859-66.
The effects of beta-antagonists (propranolol, pindolol, atenolol) and beta 1-partial agonists (xamoterol, denopamine) on the pulmonary circulation, and on the pressor response to 5-HT were investigated and compared with those of a beta-agonist, isoproterenol. These agents (at doses of 0.002-20 mg) were administrated into the isolated lung lobe perfusion system excised from mongrel dogs (7-12 kg in weight). Under standard conditions (mean pulmonary inflow pressure, 15 mmHg; mean outflow pressure, 5 mmHg), propranolol and atenolol had no effect on pulmonary vascular resistance (PVR) at the tested doses, but pindolol which has intrinsic sympathomimetic activity (ISA) and two beta 1-partial agonists significantly decreased PVR in a dose-dependent manner (each n = 7). Isoproterenol, up to a dose of 0.2 mg, markedly decreased PVR, but induced vasoconstriction in larger doses (n = 7). Propranolol and xamoterol similarly reduced the pressor response to 30 micrograms of 5-HT from a dose of 2 mg, and these inhibitory actions were greater than those of the other drugs. Pindolol and denopamine inhibited the 5-HT response in a dose of 20 mg, whereas atenolol only augmented the response in a dose-dependent manner. In conclusion, beta-antagonists with ISA (including beta 1-partial agonist activity) can dilate the pulmonary vessels in a dose-dependent manner, but not beta-antagonists without ISA. Furthermore, the 5-HT inhibitory effects caused by relatively large doses of beta-antagonists, except for atenolol, may be related to the 5-HT receptor blockade or other unknown mechanisms, including calcium influx or prostaglandin synthesis, but not to the beta-receptor blockade.
研究了β受体拮抗剂（普萘洛尔、吲哚洛尔、阿替洛尔）和β1部分激动剂（扎莫特罗、多巴胺）对肺循环以及对5-羟色胺（5-HT）升压反应的影响，并与β激动剂异丙肾上腺素进行了比较。将这些药物（剂量为0.002 - 20毫克）注入从杂种犬（体重7 - 12千克）切除的离体肺叶灌注系统。在标准条件下（平均肺流入压15毫米汞柱；平均流出压5毫米汞柱），在所测试的剂量下，普萘洛尔和阿替洛尔对肺血管阻力（PVR）无影响，但具有内在拟交感活性（ISA）的吲哚洛尔和两种β1部分激动剂以剂量依赖方式显著降低PVR（每组n = 7）。剂量高达0.2毫克的异丙肾上腺素显著降低PVR，但大剂量时会诱导血管收缩（n = 7）。普萘洛尔和扎莫特罗从2毫克剂量起类似地降低了对30微克5-HT的升压反应，且这些抑制作用大于其他药物。吲哚洛尔和多巴胺在20毫克剂量时抑制5-HT反应，而阿替洛尔仅以剂量依赖方式增强该反应。总之，具有ISA（包括β1部分激动剂活性）的β受体拮抗剂可剂量依赖性地扩张肺血管，但无ISA的β受体拮抗剂则不然。此外，除阿替洛尔外，相对大剂量β受体拮抗剂引起的5-HT抑制作用可能与5-HT受体阻断或其他未知机制有关，包括钙内流或前列腺素合成，而非β受体阻断。
