l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , |
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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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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embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132153029591040 |