title: An orally active angiotensin-(1-7) inclusion compound and exercise training produce similar cardiovascular effects in spontaneously hypertensive rats.
abstract: Low angiotensin-(1-7) (Ang-(1-7)) concentration is observed in some cardiovascular diseases and exercise training seems to restore its concentration in the heart. Recently, a novel formulation of an orally active Ang-(1-7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronically administered in experimental models of cardiovascular diseases. The present study examined whether chronic administration of HPB-CD/Ang-(1-7) produces beneficial cardiovascular effects in spontaneously hypertensive rats (SHR), as well as to compare the results obtained with those produced by exercise training. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1-7) (corresponding to 30μgkg(-1)day(-1) of Ang-(1-7)) by gavage, concomitantly or not to exercise training (treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis in the heart were performed. Chronic HPB-CD/Ang-(1-7) decreased arterial blood pressure (BP) and heart rate in SHR. The inclusion compound significantly improved left ventricular (LV) end-diastolic pressure, restored the maximum and minimum derivatives (dP/dT) and decreased cardiac hypertrophy index in SHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heart and vessels and the SAP variability, as well as increasing parasympathetic modulation and HR variability. Overall results were similar to those obtained with exercise training. These results show that chronic treatment with the HPB-CD/Ang-(1-7) inclusion compound produced beneficial effects in SHR resembling the ones produced by exercise training. This observation reinforces the potential cardiovascular therapeutic effect of this novel peptide formulation.
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, 395 Av. Princesa Isabel, Porto Alegre, Rio Grande do Sul 90620-001, Brazil; INCT-Nanobiofar-Universidade Federal de Minas Gerais, 6627 Av. Antônio Carlos, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Mariane
authors.initials: M
authors.lastname: Bertagnolli
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, 395 Av. Princesa Isabel, Porto Alegre, Rio Grande do Sul 90620-001, Brazil.
authors.forename: Karina R
authors.initials: KR
authors.lastname: Casali
authors.affiliation: Instituto de Física e Química, Universidade Federal de Itajubá, 1303 Av. BPS, Itajubá, Minas Gerais 37500-903, Brazil; INCT-Nanobiofar-Universidade Federal de Minas Gerais, 6627 Av. Antônio Carlos, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Frederico B
authors.initials: FB
authors.lastname: De Sousa
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, 395 Av. Princesa Isabel, Porto Alegre, Rio Grande do Sul 90620-001, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, 245 Rua Sarmento Leite, Porto Alegre, Rio Grande do Sul 90050-170, Brazil.
authors.forename: Katya
authors.initials: K
authors.lastname: Rigatto
authors.affiliation: INCT-Nanobiofar-Universidade Federal de Minas Gerais, 6627 Av. Antônio Carlos, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Lenice
authors.initials: L
authors.lastname: Becker
authors.affiliation: INCT-Nanobiofar-Universidade Federal de Minas Gerais, 6627 Av. Antônio Carlos, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Sergio H S
authors.initials: SH
authors.lastname: Santos
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, 395 Av. Princesa Isabel, Porto Alegre, Rio Grande do Sul 90620-001, Brazil.
authors.forename: Lucinara D
authors.initials: LD
authors.lastname: Dias
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, 395 Av. Princesa Isabel, Porto Alegre, Rio Grande do Sul 90620-001, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, 245 Rua Sarmento Leite, Porto Alegre, Rio Grande do Sul 90050-170, Brazil.
authors.forename: Graziela
authors.initials: G
authors.lastname: Pinto
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, 395 Av. Princesa Isabel, Porto Alegre, Rio Grande do Sul 90620-001, Brazil.
authors.forename: Daniela R
authors.initials: DR
authors.lastname: Dartora
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, and Department of Medicine, Faculty of Medicine, Universidade Federal do Rio Grande do Sul, 2350 Rua Ramiro Barcelos, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil.
authors.forename: Beatriz D
authors.initials: BD
authors.lastname: Schaan
authors.affiliation: INCT-Nanobiofar-Universidade Federal de Minas Gerais, 6627 Av. Antônio Carlos, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Ruben Dario Sinisterra
authors.initials: RD
authors.lastname: Milan
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, 395 Av. Princesa Isabel, Porto Alegre, Rio Grande do Sul 90620-001, Brazil; Heart Institute/Universidade de São Paulo, 44 Av. Dr. Enéas de Carvalho Aguiar, São Paulo, São Paulo, 05403-900, Brazil; INCT-Nanobiofar-Universidade Federal de Minas Gerais, 6627 Av. Antônio Carlos, Belo Horizonte, Minas Gerais 31270-901, Brazil.
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Irigoyen
authors.affiliation: Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia, 395 Av. Princesa Isabel, Porto Alegre, Rio Grande do Sul 90620-001, Brazil; INCT-Nanobiofar-Universidade Federal de Minas Gerais, 6627 Av. Antônio Carlos, Belo Horizonte, Minas Gerais 31270-901, Brazil. Electronic address: robsonsant@gmail.com.
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000803:Angiotensin I / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001794:Blood Pressure; D003131:Combined Modality Therapy; D004353:Drug Evaluation, Preclinical; D005079:Excipients / Q000008:administration & dosage*; D005081:Exercise Therapy; D006339:Heart Rate; D006973:Hypertension / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010805:Physical Conditioning, Animal; D051381:Rats; D011918:Rats, Inbred SHR; D017725:Ventricular Pressure; D047392:beta-Cyclodextrins / Q000008:administration & dosage*
chemical_list: D000959:Antihypertensive Agents; D005079:Excipients; D010446:Peptide Fragments; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: Autonomic control; Cardiac function; Exercise training; Hypertension; Renin–angiotensin system