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

Jorge Eduardo Chang Estrada; Keuri Eleutério Rodrigues; Anderson Maciel; Cahy Manoel Bannwart; Wictória Farias Dias; Moisés Hamoy; Russolina Benedeta Zingali; Andreimar Martins Soares; Carolina Heitmann Mares Azevedo Ribeiro; Raquel Fernanda Gerlach; Marta Chagas Monteiro; Alejandro Ferraz Prado

doi:10.3390/toxins14110766

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

Toxins (Basel). 2022 Nov 5;14(11):766. doi: 10.3390/toxins14110766.

Authors

Affiliations

¹ Laboratory of Pharmacology and Toxicology of Cardiovascular System, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil.
² 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.
³ Center of Study of Biomolecules Applied in Medicine (CEBio), Oswaldo Cruz Foundation (Fiocruz Rondônia), Federal University of Rondônia, Porto Velho 76812-245, RO, Brazil.
⁴ Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil.
⁵ São Lucas University Center, Porto Velho 76805-846, RO, Brazil.
⁶ Laboratory of Hematology, Faculty of Pharmacy, Institute of Health Science, Federal University of Pará, Belém 66075-110, PA, Brazil.
⁷ Department of Basic and Oral Biology, Faculty of Dentistry of Ribeirao Preto, University of São Paulo (FORP/USP), Ribeirao Preto 14040-904, SP, Brazil.
⁸ Laboratory of Clinical Immunology and Oxidative Stress, Pharmacy Faculty, Institute of Health Science, Federal University of Pará, Belém 66075-110, PA, Brazil.

Abstract

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, p < 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, p < 0.05), without changing the hematological profile (platelets: 758 ± 67; leukocytes: 3980 ± 326 versus 758 ± 75; 4400 ± 800, 2K1C Vehicle, p > 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, p < 0.05) and fibrosis (3.9 ± 0.2 versus 7.4 ± 0.7, 2K1C Vehicle, p < 0.05). We concluded that BmooMPα-I improved blood pressure levels and cardiac remodeling, having a cardioprotective effect.

Keywords: arrhythmia; cardioprotective effect; fibrosis; remodeling; snake venom.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Pressure
Bothrops*
Crotalid Venoms* / pharmacology
Heart Rate
Hypertension, Renovascular* / drug therapy
Metalloproteases / pharmacology
Rats
Rats, Wistar
Ventricular Remodeling

Substances

Crotalid Venoms
Metalloproteases

Grants and funding

This work had partial financial support from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP Grant number 2014-23888-0), Conselho Nacional de Desenvolvimento científico e Tecnológico (CNPq), Coordenação de Aperfeiçonamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance Code 001. The APC payment was supported by Pró-reitoria de Pesquisa e Pós-Graduação (PROPESP) from Federal University of Pará (UFPA).