title: In vitro ACE-inhibitory peptide KGYGGVSLPEW facilitates noradrenaline release from sympathetic nerve terminals: Relationship with the lack of antihypertensive effect on spontaneous hypertensive rats.
abstract: This study aimed to validate the antihypertensive activity of the angiotensin-converting enzyme (ACE)-inhibitor whey protein hydrolysate (WPH) obtained through the action of proteolytic enzymes from Cynara Cardunculus. The antihypertensive activity of WPH fractions containing peptides with molecular weight below 3kDa (Whey<3kDa) and 1kDa (Whey<1kDa) along with the antihypertensive activity of three potent ACE-inhibitory peptide sequences (DKVGINYW, DAQSAPLRVY and KGYGGVSLPEW), previously identified in WPH, were also investigated. In parallel, the influence of KGYGGVSLPEW (the most potent ACE-inhibitory peptide sequence) on AT1 receptors (a common pharmacological target of antihypertensive therapies beyond ACE), was evaluated. The effect of WPH and fractions (300mg/kg) and peptide sequences (5mg/kg) on systolic, diastolic and mean blood pressure was evaluated by telemetry on spontaneously hypertensive rats (SHR), after single oral administration. Despite their ACE-inhibitory effect in vitro, neither WPH, Whey <3kDa, Whey <1kDa or peptide sequences exhibited antihypertensive activity. In addition, KGYGGVSLPEW was not only devoid of AT1 receptor antagonism but, on the contrary, had a similar effect to that of Ang II by facilitating the noradrenaline release from sympathetic nerve terminals. In vitro ACE blockade does not always correlate with antihypertensive activity and food-derived peptides cannot be classified as antihypertensive agents based exclusively on in vitro assays. The absence of an antihypertensive effect may also be a result of the interaction of these compounds with other components of the systems involved in the blood pressure control.
authors.affiliation: Departamento de Bioquímica, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Marques
authors.affiliation: Centro de Biotecnologia e Química Fina - Laboratório Associado de Estado, Universidade Católica Portuguesa, Rua Arquiteto Lobão Vital, 4202-401 Porto, Portugal.
authors.forename: Maria Manuela
authors.initials: MM
authors.lastname: Amorim
authors.affiliation: Centro de Biotecnologia e Química Fina - Laboratório Associado de Estado, Universidade Católica Portuguesa, Rua Arquiteto Lobão Vital, 4202-401 Porto, Portugal.
authors.forename: Joana Odila
authors.initials: JO
authors.lastname: Pereira
authors.affiliation: Biotério, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Guardão
authors.affiliation: Departamento de Bioquímica, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Júlio Amaral de Carvalho n° 245, 4200-135 Porto, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Martins
authors.affiliation: Centro de Biotecnologia e Química Fina - Laboratório Associado de Estado, Universidade Católica Portuguesa, Rua Arquiteto Lobão Vital, 4202-401 Porto, Portugal.
authors.forename: Manuela Estevez
authors.initials: ME
authors.lastname: Pintado
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; MedinUP, Center for Drug Discovery and Innovative Medicines, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moura
authors.affiliation: Departamento de Bioquímica, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; CINTESIS, Centro de Investigação em Tecnologias e Sistemas de Informação em Saúde, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Conceição
authors.initials: C
authors.lastname: Calhau
authors.affiliation: Departamento de Farmacologia e Terapêutica, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: helderp@med.up.pt.
authors.forename: Hélder
authors.initials: H
authors.lastname: Pinheiro
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D031942:Cynara / Q000737:chemistry*; D009417:Nerve Tissue / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010940:Plant Proteins / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D010940:Plant Proteins; D044140:Receptor, Angiotensin, Type 1; D009638:Norepinephrine
keywords: Angiotensin-converting enzyme; Antihypertensive; Bioactive peptides; Hypertension; Mechanisms of action; Whey