Bönner G, Preis S, Schunk U, Toussaint C, Kaufmann W
Department of Internal Medicine II, University of Cologne, Merheim Hospital, F.R.G.
J Cardiovasc Pharmacol. 1990;15 Suppl 6:S46-56.
In our studies, we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intra-arterially (40-6,050 pM/kg) and was infused intra-arterially (40-6,050 pM/kg/min). The investigations were performed in 21 normotensive and 15 hypertensive patients. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol of Na/day), salt loading (300 mmol of Na/day), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 X 1 mg), indomethacin (2 X 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure in a dose-related manner by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, beta-adrenoceptors, histamine-1 receptors, and prostaglandins. ACE inhibitors protentiate the blood pressure-lowering effect of bradykinin approximately 20- to 50-fold. In the case of intra-arterial injection of bradykinin, only 2-5% of the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From these experiments, a pulmonary clearance rate of bradykinin of over 95% can be calculated. In the pulmonary arteries, bradykinin has no effect on vascular resistance. In patients suffering from primary or renovascular hypertension, the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE inhibitors was not altered in the hypertensives. In patients suffering from borderline hypertension or primary hyperaldosteronism, bradykinin caused the same blood pressure lowering effect as in the normotensives.
在我们的研究中，我们调查了缓激肽在正常血压和高血压受试者体内的血管减压作用。缓激肽通过静脉内和动脉内注射（40 - 6050皮摩尔/千克）以及动脉内输注（40 - 6050皮摩尔/千克/分钟）给药。研究在21名正常血压患者和15名高血压患者中进行。缓激肽注射在以下药理学干预后进行：限盐（每日10毫摩尔钠）、盐负荷（每日300毫摩尔钠）、卡托普利（50毫克）、雷米普利（5毫克）、赖诺普利（20毫克）、酮替芬（2×1毫克）、吲哚美辛（2×50毫克）和普萘洛尔（80毫克）。结果表明，缓激肽通过显著降低外周血管阻力以剂量相关的方式降低血压。血压降低与激肽浓度的增加密切相关。缓激肽的这种作用似乎与钠代谢、β - 肾上腺素能受体、组胺 - 1受体和前列腺素的变化无关。血管紧张素转换酶（ACE）抑制剂使缓激肽的降压作用增强约20至50倍。在动脉内注射缓激肽的情况下，只需静脉内使用剂量的2%至5%的缓激肽就能产生相同程度的血压下降。从这些实验中，可以计算出缓激肽的肺部清除率超过95%。在肺动脉中，缓激肽对血管阻力没有影响。在原发性或肾血管性高血压患者中，对缓激肽的血压反应增强。ACE抑制剂对缓激肽的增强作用在高血压患者中未改变。在临界高血压或原发性醛固酮增多症患者中，缓激肽引起的血压降低作用与正常血压患者相同。
