BmooMPα-I, a Metalloproteinase Isolated from Bothrops moojeni Venom, Reduces Blood Pressure, Reverses Left Ventricular Remodeling and Improves Cardiac Electrical Conduction in Rats with Renovascular Hypertension

• Published in: Toxins Vol. 14; no. 11; p. 766
• Main Authors: Estrada, Jorge Eduardo Chang, Rodrigues, Keuri Eleutério, Maciel, Anderson, Bannwart, Cahy Manoel, Dias, Wictória Farias, Hamoy, Moisés, Zingali, Russolina Benedeta, Soares, Andreimar Martins, Ribeiro, Carolina Heitmann Mares Azevedo, Gerlach, Raquel Fernanda, Monteiro, Marta Chagas, Prado, Alejandro Ferraz
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05-11-2022; MDPI
• Subjects: Angiotensin; Angiotensin I; Animal models; Animals; Antihypertensives; arrhythmia; Aspartic acid; Blood Pressure; Bothrops; Bradykinin; cardioprotective effect; Chromatography; Collagen; Crotalid Venoms - pharmacology; Diastolic pressure; Drug dosages; EKG; Electrical conduction; Electrocardiography; Fibrosis; Heart Rate; Hematology; Hypertension; Hypertension, Renovascular - drug therapy; Hypertrophy; Kininogens; Leukocytes; Metalloproteases - pharmacology; Metalloproteinase; Peptides; Rats; Rats, Wistar; remodeling; Renal artery; snake venom; Stenosis; Systolic pressure; Thickness; Venom; Ventricle; Ventricular Remodeling; snake venom; remodeling; fibrosis; cardioprotective effect; arrhythmia
• ISSN: 2072-6651; 2072-6651
• 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.