l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats

Detalhes bibliográficos
Autor(a) principal: Leal, Joana
Data de Publicação: 2018
Outros Autores: Teixeira-Santos, Luísa, Pinho, Dora, Afonso, Joana, Carvalho, Jorge, de Lourdes Bastos, Maria, Albino-Teixeira, António, Fraga, Sónia, Sousa, Teresa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6320
Resumo: We evaluated whether l-proline (Pro) supplementation improves redox status and nitric oxide (NO) bioavailability and prevents or delays angiotensin II (AngII)-induced hypertension. Male Sprague-Dawley rats were distributed to four experimental groups: Pro + AngII (Pro-Ang), Pro + Saline (Pro-Sal), Vehicle + AngII (Veh-Ang) and Veh + Saline (Veh-Sal). Pro solution (2 g.kg-1·day-1) or water (vehicle) were orally administered, from day 0 to day 21. AngII (200 ng.kg-1.min-1) or saline were infused (s.c.) from day 7 to day 21. Systolic blood pressure (SBP) was measured by the tail-cuff method. From day 20-21, animals were kept on metabolic cages for 24h-urine collection. On day 21, urine and blood were collected for further quantification of redox status biomarkers, NO-related markers (urinary nitrates and nitrites, U-NOx; plasma asymmetric dimethylarginine, P-ADMA), metabolic and renal parameters. Pro prevented the AngII-induced SBP rise [mean (95% CI), Day 19: Pro-AngII, 137 (131; 143) vs. Veh-AngII, 157 (151; 163) mm Hg, P < 0.001]. Pro-AngII rats also had increased values of U-NOx, systemic and urinary total antioxidant status (TAS), urinary H2O2 and plasma urea, as well as reduced P-ADMA and unaltered urinary isoprostanes. Plasma Pro was inversely correlated with P-ADMA (r = -0.52, p = 0.0009) and positively correlated with urinary TAS (r = 0.55, p = 0.0005) which, in turn, was inversely correlated with P-ADMA (r = -0.56, p = 0.0004). Furthermore, urinary H2O2 values decreased across P-ADMA tertiles (p for linear trend = 0.023). These results suggest that Pro reduces P-ADMA levels and improves redox status, thereby increasing NO bioavailability and counteracting the AngII-induced SBP rise. H2O2 and TAS modulation by Pro may contribute to the reduced P-ADMA concentration.
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spelling l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in ratsAngiotensin IIAnimalsBiological AvailabilityBlood PressureHypertensionMaleNitric OxideProlineRatsRats, Sprague-DawleyDietary SupplementsDoenças Cardio e Cérebro-vascularesWe evaluated whether l-proline (Pro) supplementation improves redox status and nitric oxide (NO) bioavailability and prevents or delays angiotensin II (AngII)-induced hypertension. Male Sprague-Dawley rats were distributed to four experimental groups: Pro + AngII (Pro-Ang), Pro + Saline (Pro-Sal), Vehicle + AngII (Veh-Ang) and Veh + Saline (Veh-Sal). Pro solution (2 g.kg-1·day-1) or water (vehicle) were orally administered, from day 0 to day 21. AngII (200 ng.kg-1.min-1) or saline were infused (s.c.) from day 7 to day 21. Systolic blood pressure (SBP) was measured by the tail-cuff method. From day 20-21, animals were kept on metabolic cages for 24h-urine collection. On day 21, urine and blood were collected for further quantification of redox status biomarkers, NO-related markers (urinary nitrates and nitrites, U-NOx; plasma asymmetric dimethylarginine, P-ADMA), metabolic and renal parameters. Pro prevented the AngII-induced SBP rise [mean (95% CI), Day 19: Pro-AngII, 137 (131; 143) vs. Veh-AngII, 157 (151; 163) mm Hg, P < 0.001]. Pro-AngII rats also had increased values of U-NOx, systemic and urinary total antioxidant status (TAS), urinary H2O2 and plasma urea, as well as reduced P-ADMA and unaltered urinary isoprostanes. Plasma Pro was inversely correlated with P-ADMA (r = -0.52, p = 0.0009) and positively correlated with urinary TAS (r = 0.55, p = 0.0005) which, in turn, was inversely correlated with P-ADMA (r = -0.56, p = 0.0004). Furthermore, urinary H2O2 values decreased across P-ADMA tertiles (p for linear trend = 0.023). These results suggest that Pro reduces P-ADMA levels and improves redox status, thereby increasing NO bioavailability and counteracting the AngII-induced SBP rise. H2O2 and TAS modulation by Pro may contribute to the reduced P-ADMA concentration.The authors acknowledge funding under project “NORTE-07-0124- FEDER-000001 – Neurodegenerative Disorders”, co-funded by North Portugal Regional Operational Programme (ON.2—O Novo Norte), under QREN (National Strategic Reference Framework) through FEDER (European Regional Development Fund), and by FCT (Fundação para a Ciência e a Tecnologia, Portugal). This study was also funded by the Program PT2020 (project 007265 -UID/QUI/50006/2013) supported by FCT and FEDER. Teresa Sousa and Sónia Fraga were funded by FCT and POPH/FSE (EC) (Human Potential Operational Programme/ European Social Fund (European Comission) (Ciência 2008 Contract). Teresa Sousa is currently funded by FCT (SFRH/BPD/112005/2015). Luísa Teixeira-Santos is funded by University of Porto/Faculty of Medicine and by ESF – European Social Fund, through NORTE2020 – North Portugal Regional Operational Programme (NORTE-08-5369- FSE-000011-Doctoral Programmes). Fig. 6. Mean (95% CI) plasma values of ADMA (A) and L-Arginine/ADMA ratio (B) for the different experimental groups (Veh-Sal, n=9; Pro-Sal, n=8; Veh-Ang, n=10; Pro-Ang, n=10) at the end of the experiment (day 21). Data were analysed with single measure parametric analysis (ANOVA), with 2 experimental factors (Pro and Ang) and a blocking factor. P-values obtained from the analysis for each factor and interaction of factors are presented in tables below the graphs. Results from multiple comparison procedures, performed as described in section 2.7, are indicated on the graph. J. Leal et al. Nitric Oxide 82 (2019) 1–11.ElsevierRepositório Científico do Instituto Nacional de SaúdeLeal, JoanaTeixeira-Santos, LuísaPinho, DoraAfonso, JoanaCarvalho, Jorgede Lourdes Bastos, MariaAlbino-Teixeira, AntónioFraga, SóniaSousa, Teresa2019-03-26T18:23:37Z2018-11-102018-11-10T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6320engNitric Oxide. 2019 Jan 1;82:1-11. doi: 10.1016/j.niox.2018.10.007. Epub 2018 Nov 10.1089-860310.1016/j.niox.2018.10.007info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:21Zoai:repositorio.insa.pt:10400.18/6320Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:40:58.172752Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats
title l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats
spellingShingle l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats
Leal, Joana
Angiotensin II
Animals
Biological Availability
Blood Pressure
Hypertension
Male
Nitric Oxide
Proline
Rats
Rats, Sprague-Dawley
Dietary Supplements
Doenças Cardio e Cérebro-vasculares
title_short l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats
title_full l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats
title_fullStr l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats
title_full_unstemmed l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats
title_sort l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats
author Leal, Joana
author_facet Leal, Joana
Teixeira-Santos, Luísa
Pinho, Dora
Afonso, Joana
Carvalho, Jorge
de Lourdes Bastos, Maria
Albino-Teixeira, António
Fraga, Sónia
Sousa, Teresa
author_role author
author2 Teixeira-Santos, Luísa
Pinho, Dora
Afonso, Joana
Carvalho, Jorge
de Lourdes Bastos, Maria
Albino-Teixeira, António
Fraga, Sónia
Sousa, Teresa
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Leal, Joana
Teixeira-Santos, Luísa
Pinho, Dora
Afonso, Joana
Carvalho, Jorge
de Lourdes Bastos, Maria
Albino-Teixeira, António
Fraga, Sónia
Sousa, Teresa
dc.subject.por.fl_str_mv Angiotensin II
Animals
Biological Availability
Blood Pressure
Hypertension
Male
Nitric Oxide
Proline
Rats
Rats, Sprague-Dawley
Dietary Supplements
Doenças Cardio e Cérebro-vasculares
topic Angiotensin II
Animals
Biological Availability
Blood Pressure
Hypertension
Male
Nitric Oxide
Proline
Rats
Rats, Sprague-Dawley
Dietary Supplements
Doenças Cardio e Cérebro-vasculares
description We evaluated whether l-proline (Pro) supplementation improves redox status and nitric oxide (NO) bioavailability and prevents or delays angiotensin II (AngII)-induced hypertension. Male Sprague-Dawley rats were distributed to four experimental groups: Pro + AngII (Pro-Ang), Pro + Saline (Pro-Sal), Vehicle + AngII (Veh-Ang) and Veh + Saline (Veh-Sal). Pro solution (2 g.kg-1·day-1) or water (vehicle) were orally administered, from day 0 to day 21. AngII (200 ng.kg-1.min-1) or saline were infused (s.c.) from day 7 to day 21. Systolic blood pressure (SBP) was measured by the tail-cuff method. From day 20-21, animals were kept on metabolic cages for 24h-urine collection. On day 21, urine and blood were collected for further quantification of redox status biomarkers, NO-related markers (urinary nitrates and nitrites, U-NOx; plasma asymmetric dimethylarginine, P-ADMA), metabolic and renal parameters. Pro prevented the AngII-induced SBP rise [mean (95% CI), Day 19: Pro-AngII, 137 (131; 143) vs. Veh-AngII, 157 (151; 163) mm Hg, P < 0.001]. Pro-AngII rats also had increased values of U-NOx, systemic and urinary total antioxidant status (TAS), urinary H2O2 and plasma urea, as well as reduced P-ADMA and unaltered urinary isoprostanes. Plasma Pro was inversely correlated with P-ADMA (r = -0.52, p = 0.0009) and positively correlated with urinary TAS (r = 0.55, p = 0.0005) which, in turn, was inversely correlated with P-ADMA (r = -0.56, p = 0.0004). Furthermore, urinary H2O2 values decreased across P-ADMA tertiles (p for linear trend = 0.023). These results suggest that Pro reduces P-ADMA levels and improves redox status, thereby increasing NO bioavailability and counteracting the AngII-induced SBP rise. H2O2 and TAS modulation by Pro may contribute to the reduced P-ADMA concentration.
publishDate 2018
dc.date.none.fl_str_mv 2018-11-10
2018-11-10T00:00:00Z
2019-03-26T18:23:37Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/6320
url http://hdl.handle.net/10400.18/6320
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Nitric Oxide. 2019 Jan 1;82:1-11. doi: 10.1016/j.niox.2018.10.007. Epub 2018 Nov 10.
1089-8603
10.1016/j.niox.2018.10.007
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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