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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\u2009\u00b5M and 40\u2009\u00b5M, a 10-fold greater inhibition than observed with PepTry (60\u2009\u00b5M) and PepChy (400\u2009\u00b5M). These molecules also inhibited angiotensin converting enzyme (ACE) with IC<jats:sub>50<\/jats:sub> values of 54.6\u2009\u00b1\u20092.9; 24.7\u2009\u00b1\u20091.1; and 24.4\u2009\u00b1\u20091.1\u2009\u00b5M, 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.<\/jats:p>","DOI":"10.1038\/s41598-020-66624-3","type":"journal-article","created":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T10:04:02Z","timestamp":1594807442000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats"],"prefix":"10.1038","volume":"10","author":[{"given":"Maria Alzira Garcia","family":"de Freitas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia Oda","family":"Amaral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice da Cunha Morales","family":"\u00c1lvares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandriele Aires","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azadeh","family":"Mehdad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Elias","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9806-4376","authenticated-orcid":false,"given":"Amanda S\u00e1 Martins","family":"Bessa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9738-3412","authenticated-orcid":false,"given":"Marcelo Henrique Soller","family":"Ramada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara Marques","family":"Naves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Nobre Ribeiro","family":"Pontes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Rodrigues","family":"Pedrino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7562-4980","authenticated-orcid":false,"given":"Sonia Maria","family":"de Freitas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,15]]},"reference":[{"key":"66624_CR1","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1097\/00004872-200311000-00002","volume":"21","author":"JA Whitworth","year":"2003","unstructured":"Whitworth, J. A. 2003 World Health Organization (WHO)\/International Society of Hypertension (ISH) statement on management of hypertension. Journal of hypertension 21, 1983\u20131992, https:\/\/doi.org\/10.1097\/00004872-200311000-00002 (2003).","journal-title":"Journal of hypertension"},{"key":"66624_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jacc.2017.04.052","volume":"70","author":"GA Roth","year":"2017","unstructured":"Roth, G. A. et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. Journal of the American College of Cardiology 70, 1\u201325, https:\/\/doi.org\/10.1016\/j.jacc.2017.04.052 (2017).","journal-title":"Journal of the American College of Cardiology"},{"key":"66624_CR3","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1007\/s11906-013-0340-9","volume":"15","author":"S Bromfield","year":"2013","unstructured":"Bromfield, S. & Muntner, P. 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