Journal Article

Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats

Castro, Carlos Henrique, de Freitas, Maria Alzira Garcia, de Freitas, Sonia Maria, Mehdad, Azadeh, Pedrino, Gustavo Rodrigues, Bessa, Amanda Sá Martins, Ramada, Marcelo Henrique Soller, Álvares, Alice da Cunha Morales, Amaral, Nathalia Oda, de Oliveira, Sandriele Aires, Pontes, Carolina Nobre Ribeiro, Honda, Diego Elias, Naves, Lara Marques

2020

Overview

Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC 50 values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/443/592/75/243 / 631/45/56 / 64 / 82 / 82/16 / 82/83 / Angiotensin / Animals / Antihypertensive Agents - chemistry / Antihypertensive Agents - pharmacology / Antihypertensives / Aorta / Binding Sites / Blood pressure / Blood Pressure - drug effects / Chymotrypsin / Chymotrypsin - chemistry / Chymotrypsin - metabolism / Conductance / Coronary Vessels - drug effects / Coronary Vessels - physiopathology / Enzyme Inhibitors - chemistry / Enzyme Inhibitors - pharmacology / Humanities and Social Sciences / Hypertension / Hypertension - drug therapy / Hypertension - enzymology / Hypertension - physiopathology / Male / Molecular Docking Simulation / multidisciplinary / Myocardial Contraction - drug effects / NG-Nitroarginine Methyl Ester - chemistry / NG-Nitroarginine Methyl Ester - pharmacology / Nitric oxide / Nitric Oxide Synthase Type III - antagonists & inhibitors / Nitric Oxide Synthase Type III - chemistry / Nitric Oxide Synthase Type III - metabolism / Nitric-oxide synthase / Peptides / Peptides - chemical synthesis / Peptides - pharmacology / Peptidyl-dipeptidase A / Peptidyl-Dipeptidase A - chemistry / Peptidyl-Dipeptidase A - metabolism / Protein Binding / Protein Interaction Domains and Motifs / Protein Structure, Secondary / Proteinase inhibitors / Rats / Rats, Inbred SHR / Rats, Wistar / Rodents / Science / Science (multidisciplinary) / Side effects / Trypsin / Trypsin - chemistry / Trypsin - metabolism / Trypsin Inhibitor, Bowman-Birk Soybean - chemistry / Trypsin Inhibitor, Bowman-Birk Soybean - pharmacology / Vasodilation / Vasodilation - drug effects