Montenegro Marcelo F, Pessa Lisandra R, Tanus-Santos Jose E
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil.
Eur J Pharmacol. 2009 Apr 1;607(1-3):173-7. doi: 10.1016/j.ejphar.2009.02.015. Epub 2009 Feb 20.
Genistein produces antihypertensive and beneficial cardiovascular effects, although the mechanisms for these effects are not known. We examined whether genistein inhibits the in vivo responses to angiotensin I or enhances the responses to bradykinin in anaesthetized rats as a result of angiotensin-converting enzyme inhibition. We have also studied the in vitro effects produced by genistein on the angiotensin-converting enzyme activity. We measured the changes in systemic arterial pressure induced by angiotensin I in doses of 0.03 to 10 microg/kg, by angiotensin II in doses of 0.01 to 3 microg/kg, and to bradykinin in doses of 0.03 to 10 microg/kg in anaesthetized rats pretreated with vehicle (controls), or a single i.v. dose of genistein 25 mg/kg, or daily genistein 25 mg/kg i.v for two days, or a single i.v. dose of captopril 2 mg/kg. Plasma angiotensin-converting enzyme activity was determined in controls and genistein-treated rats using a fluorometric method. The effects of genistein (3-300 micromol/l) on in vitro angiotensin-converting enzyme activity were assessed by adding genistein to plasma samples and measuring angiotensin-converting enzyme activity. We found significant lower angiotensin-converting enzyme activity in plasma samples from rats pretreated with genistein compared with those found in the Control group (77.7+/-8.1 his-leu nmol/min/ml and 108.7+/-8.4 his-leu nmol/min/ml, respectively; P=0.01). The incubation of genistein with plasma samples showed that genistein decreased the angiotensin-converting enzyme activity in plasma in a concentration-dependent manner (P<0.01). These findings indicate that genistein inhibits the angiotensin-converting enzyme in vivo and in vitro and may explain, at least in part, the antihypertensive and beneficial vascular effects produced by genistein.
染料木黄酮具有抗高血压和有益心血管的作用，尽管这些作用的机制尚不清楚。我们研究了染料木黄酮是否通过抑制血管紧张素转换酶来抑制麻醉大鼠体内对血管紧张素I的反应或增强对缓激肽的反应。我们还研究了染料木黄酮对血管紧张素转换酶活性的体外作用。我们测量了在给予载体（对照组）、单次静脉注射25mg/kg染料木黄酮、连续两天每天静脉注射25mg/kg染料木黄酮或单次静脉注射2mg/kg卡托普利预处理的麻醉大鼠中，0.03至10μg/kg剂量的血管紧张素I、0.01至3μg/kg剂量的血管紧张素II以及0.03至10μg/kg剂量的缓激肽所诱导的全身动脉压变化。使用荧光法测定对照组和染料木黄酮处理大鼠的血浆血管紧张素转换酶活性。通过向血浆样本中添加染料木黄酮并测量血管紧张素转换酶活性来评估染料木黄酮（3 - 300μmol/L）对体外血管紧张素转换酶活性的影响。我们发现，与对照组相比，用染料木黄酮预处理的大鼠血浆样本中的血管紧张素转换酶活性显著降低（分别为77.7±8.1 his-leu nmol/min/ml和108.7±8.4 his-leu nmol/min/ml；P = 0.01）。染料木黄酮与血浆样本的孵育表明，染料木黄酮以浓度依赖性方式降低血浆中的血管紧张素转换酶活性（P < 0.01）。这些发现表明，染料木黄酮在体内和体外均抑制血管紧张素转换酶，这可能至少部分解释了染料木黄酮产生的抗高血压和有益血管作用。
