Laboratory of Pharmacology and Toxicology of Cardiovascular System, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil.
Laboratory of Hemostasis and Venoms, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
Toxins (Basel). 2022 Nov 5;14(11):766. doi: 10.3390/toxins14110766.
BmooMPα-I has kininogenase activity, cleaving kininogen releasing bradykinin and can hydrolyze angiotensin I at post-proline and aspartic acid positions, generating an inactive peptide. We evaluated the antihypertensive activity of BmooMPα-I in a model of two-kidney, one-clip (2K1C). Wistar rats were divided into groups: Sham, who underwent sham surgery, and 2K1C, who suffered stenosis of the right renal artery. In the second week of hypertension, we started treatment (Vehicle, BmooMPα-I and Losartan) for two weeks. We performed an electrocardiogram and blood and heart collection in the fourth week of hypertension. The 2K1C BmooMPα-I showed a reduction in blood pressure (systolic pressure: 131 ± 2 mmHg; diastolic pressure: 84 ± 2 mmHg versus 174 ± 3 mmHg; 97 ± 4 mmHg, 2K1C Vehicle, < 0.05), improvement in electrocardiographic parameters (Heart Rate: 297 ± 4 bpm; QRS: 42 ± 0.1 ms; QT: 92 ± 1 ms versus 332 ± 6 bpm; 48 ± 0.2 ms; 122 ± 1 ms, 2K1C Vehicle, < 0.05), without changing the hematological profile (platelets: 758 ± 67; leukocytes: 3980 ± 326 versus 758 ± 75; 4400 ± 800, 2K1C Vehicle, > 0.05), with reversal of hypertrophy (left ventricular area: 12.1 ± 0.3; left ventricle wall thickness: 2.5 ± 0.2; septum wall thickness: 2.3 ± 0.06 versus 10.5 ± 0.3; 2.7 ± 0.2; 2.5 ± 0.04, 2K1C Vehicle, < 0.05) and fibrosis (3.9 ± 0.2 versus 7.4 ± 0.7, 2K1C Vehicle, < 0.05). We concluded that BmooMPα-I improved blood pressure levels and cardiac remodeling, having a cardioprotective effect.
BmooMPα-I 具有激肽原酶活性,可裂解激肽原释放缓激肽,并能在脯氨酸和天冬氨酸位置水解血管紧张素 I,生成无活性肽。我们在双肾一夹(2K1C)模型中评估了 BmooMPα-I 的降压活性。Wistar 大鼠分为 Sham 组(接受假手术)和 2K1C 组(右肾动脉狭窄)。在高血压的第二周,我们开始进行为期两周的治疗(Vehicle、BmooMPα-I 和 Losartan)。在高血压的第四周,我们进行了心电图检查和血液及心脏采集。2K1C BmooMPα-I 显示血压降低(收缩压:131 ± 2mmHg;舒张压:84 ± 2mmHg 与 174 ± 3mmHg;97 ± 4mmHg,2K1C Vehicle,<0.05),心电图参数改善(心率:297 ± 4bpm;QRS:42 ± 0.1ms;QT:92 ± 1ms 与 332 ± 6bpm;48 ± 0.2ms;122 ± 1ms,2K1C Vehicle,<0.05),而血液学特征无变化(血小板:758 ± 67;白细胞:3980 ± 326 与 758 ± 75;4400 ± 800,2K1C Vehicle,>0.05),左心室肥厚逆转(左心室面积:12.1 ± 0.3;左心室壁厚度:2.5 ± 0.2;室间隔壁厚度:2.3 ± 0.06 与 10.5 ± 0.3;2.7 ± 0.2;2.5 ± 0.04,2K1C Vehicle,<0.05)和纤维化(3.9 ± 0.2 与 7.4 ± 0.7,2K1C Vehicle,<0.05)。我们得出结论,BmooMPα-I 改善了血压水平和心脏重构,具有心脏保护作用。