Waldron T L, Antonaccio M J, Murthy V S
Eur J Pharmacol. 1982 Apr 23;79(3-4):283-92. doi: 10.1016/0014-2999(82)90634-3.
In conscious male New Zealand rabbits, bradykinin caused dose-dependent (0.03-1 microgram/kg i.v.) hypotension and reflex tachycardia. After inhibition of angiotensin converting enzyme (ACE, also known as kininase II) with captopril (1 mg/kg i.v.), the hypotensive effect of bradykinin was enhanced in magnitude and duration but the normally observed tachycardia was reversed to bradycardia. In rabbits treated with indomethacin to inhibit cyclooxygenase and then given captopril, the bradycardia to bradykinin reverted to tachycardia whereas the magnitude of the initial hypotensive effect was unchanged. However, inhibition of thromboxane synthetase with SQ 80,338 (1-[3-phenyl-2-propenyl]-1H-imidazole) was without effect on either bradykinin-induced hypotension or bradycardia in captopril treated rabbits. Infusion of nicotine to inhibit prostacyclin synthetase completely reversed the bradycardia induced by bradykinin in captopril-treated rabbits, an effect unrelated to ganglion blockade by nicotine since mecamylamine had no effect on the actions of bradykinin. beta-Adrenoceptor blockade with nadolol did not modify the bradycardia caused by bradykinin in captopril-treated rabbits whereas atropine methylnitrate caused a marked reduction. Captopril had no inhibitory effect on reflex tachycardia caused by nitroglycerin or acetylcholine and only reduced that caused by eledoisin. Hypotension and bradycardia resulted from giving rabbits prostacyclin (100 microgram/kg i.v.). These results suggest that the bradycardia observed in conscious rabbits to bradykinin after captopril treatment is the result of an increase in circulating bradykinin due to ACE (kininase II) inhibition leading to a vago-vagal reflex induced by the synthesis of prostaglandins, probably prostacyclin.
在清醒的雄性新西兰兔中，缓激肽引起剂量依赖性（静脉注射0.03 - 1微克/千克）的低血压和反射性心动过速。用卡托普利（静脉注射1毫克/千克）抑制血管紧张素转换酶（ACE，也称为激肽酶II）后，缓激肽的降压作用在幅度和持续时间上均增强，但通常观察到的心动过速转变为心动过缓。在用吲哚美辛抑制环氧化酶然后给予卡托普利的兔子中，对缓激肽的心动过缓转变为心动过速，而最初降压作用的幅度未改变。然而，用SQ 80,338（1 - [3 - 苯基 - 2 - 丙烯基] - 1H - 咪唑）抑制血栓素合成酶对卡托普利处理的兔子中缓激肽诱导的低血压或心动过缓均无影响。输注尼古丁抑制前列环素合成酶完全逆转了卡托普利处理的兔子中缓激肽诱导的心动过缓，该作用与尼古丁对神经节的阻断无关，因为美加明对缓激肽的作用没有影响。用纳多洛尔进行β - 肾上腺素能受体阻断并没有改变卡托普利处理的兔子中缓激肽引起的心动过缓，而硝酸甲基阿托品则使其显著降低。卡托普利对硝酸甘油或乙酰胆碱引起的反射性心动过速没有抑制作用，仅降低了eledoisin引起的反射性心动过速。给兔子静脉注射前列环素（100微克/千克）导致低血压和心动过缓。这些结果表明，卡托普利处理后清醒兔子中观察到的对缓激肽的心动过缓是由于ACE（激肽酶II）抑制导致循环缓激肽增加，进而导致由前列腺素（可能是前列环素）合成诱导的迷走 - 迷走反射的结果。
