Supplementation with the Symbiotic Formulation Prodefen<sup>®</sup> Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats
In recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main va...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/4/680 |
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| author | Pablo Méndez-Albiñana Ángel Martínez-González Laura Camacho-Rodríguez Álvaro Ferreira-Lazarte Mar Villamiel Raquel Rodrigues-Díez Gloria Balfagón Ana B. García-Redondo Mª Isabel Prieto-Nieto Javier Blanco-Rivero |
| author_facet | Pablo Méndez-Albiñana Ángel Martínez-González Laura Camacho-Rodríguez Álvaro Ferreira-Lazarte Mar Villamiel Raquel Rodrigues-Díez Gloria Balfagón Ana B. García-Redondo Mª Isabel Prieto-Nieto Javier Blanco-Rivero |
| author_sort | Pablo Méndez-Albiñana |
| collection | DOAJ |
| description | In recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main vascular beds involved in peripheral vascular resistance. For this purpose, we used spontaneously hypertensive rats, either treated or not with the commercial synbiotic formulation Prodefen<sup>®</sup> (10<sup>8</sup> colony forming units/day, 4 weeks). Prodefen<sup>®</sup> diminished systolic blood pressure and serum endotoxin, as well as the vasoconstriction elicited by electrical field stimulation (EFS), and enhanced acetic and butyric acid in fecal samples, and the vasodilation induced by the exogenous NO donor DEA-NO. Unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in rats supplemented with Prodefen<sup>®</sup>. Both neuronal NO release and neuronal NOS activity were enhanced by Prodefen<sup>®</sup>, through a hyperactivation of protein kinase (PK)A, PKC and phosphatidylinositol 3 kinase-AKT signaling pathways. The superoxide anion scavenger tempol increased both NO release and DEA-NO vasodilation only in control animals. Prodefen<sup>®</sup> caused an increase in both nuclear erythroid related factor 2 and superoxide dismutase activities, consequently reducing both superoxide anion and peroxynitrite releases. In summary, Prodefen<sup>®</sup> could be an interesting non-pharmacological approach to ameliorate hypertension. |
| first_indexed | 2024-03-09T11:14:05Z |
| format | Article |
| id | doaj.art-84b958fef86b436d9c7836093bdd8265 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T11:14:05Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-84b958fef86b436d9c7836093bdd82652023-12-01T00:34:56ZengMDPI AGAntioxidants2076-39212022-03-0111468010.3390/antiox11040680Supplementation with the Symbiotic Formulation Prodefen<sup>®</sup> Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive RatsPablo Méndez-Albiñana0Ángel Martínez-González1Laura Camacho-Rodríguez2Álvaro Ferreira-Lazarte3Mar Villamiel4Raquel Rodrigues-Díez5Gloria Balfagón6Ana B. García-Redondo7Mª Isabel Prieto-Nieto8Javier Blanco-Rivero9Department of Physiology, School of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, SpainDepartment of Physiology, School of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, SpainDepartment of Physiology, School of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, SpainGroup of Chemistry and Functionality of Carbohydrates and Derivatives, Food Science Research Institute (CIAL) (CSIC-UAM), 28049 Madrid, SpainGroup of Chemistry and Functionality of Carbohydrates and Derivatives, Food Science Research Institute (CIAL) (CSIC-UAM), 28049 Madrid, SpainDepartment of Pharmacology and Therapeutics, School of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, SpainDepartment of Physiology, School of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, SpainDepartment of Physiology, School of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, SpainResearch Institute University Hospital la Paz (IdIPaz), 28029 Madrid, SpainDepartment of Physiology, School of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, SpainIn recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main vascular beds involved in peripheral vascular resistance. For this purpose, we used spontaneously hypertensive rats, either treated or not with the commercial synbiotic formulation Prodefen<sup>®</sup> (10<sup>8</sup> colony forming units/day, 4 weeks). Prodefen<sup>®</sup> diminished systolic blood pressure and serum endotoxin, as well as the vasoconstriction elicited by electrical field stimulation (EFS), and enhanced acetic and butyric acid in fecal samples, and the vasodilation induced by the exogenous NO donor DEA-NO. Unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in rats supplemented with Prodefen<sup>®</sup>. Both neuronal NO release and neuronal NOS activity were enhanced by Prodefen<sup>®</sup>, through a hyperactivation of protein kinase (PK)A, PKC and phosphatidylinositol 3 kinase-AKT signaling pathways. The superoxide anion scavenger tempol increased both NO release and DEA-NO vasodilation only in control animals. Prodefen<sup>®</sup> caused an increase in both nuclear erythroid related factor 2 and superoxide dismutase activities, consequently reducing both superoxide anion and peroxynitrite releases. In summary, Prodefen<sup>®</sup> could be an interesting non-pharmacological approach to ameliorate hypertension.https://www.mdpi.com/2076-3921/11/4/680hypertensionsynbioticperivascular mesenteric innervationneuronal nitric oxideprotein kinase Aprotein kinase C |
| spellingShingle | Pablo Méndez-Albiñana Ángel Martínez-González Laura Camacho-Rodríguez Álvaro Ferreira-Lazarte Mar Villamiel Raquel Rodrigues-Díez Gloria Balfagón Ana B. García-Redondo Mª Isabel Prieto-Nieto Javier Blanco-Rivero Supplementation with the Symbiotic Formulation Prodefen<sup>®</sup> Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats Antioxidants hypertension synbiotic perivascular mesenteric innervation neuronal nitric oxide protein kinase A protein kinase C |
| title | Supplementation with the Symbiotic Formulation Prodefen<sup>®</sup> Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats |
| title_full | Supplementation with the Symbiotic Formulation Prodefen<sup>®</sup> Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats |
| title_fullStr | Supplementation with the Symbiotic Formulation Prodefen<sup>®</sup> Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats |
| title_full_unstemmed | Supplementation with the Symbiotic Formulation Prodefen<sup>®</sup> Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats |
| title_short | Supplementation with the Symbiotic Formulation Prodefen<sup>®</sup> Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats |
| title_sort | supplementation with the symbiotic formulation prodefen sup r sup increases neuronal nitric oxide synthase and decreases oxidative stress in superior mesenteric artery from spontaneously hypertensive rats |
| topic | hypertension synbiotic perivascular mesenteric innervation neuronal nitric oxide protein kinase A protein kinase C |
| url | https://www.mdpi.com/2076-3921/11/4/680 |
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