Manuel Sánchez

Universidad de Granada

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Juan Duarte

Universidad de Granada

Miguel Romero

Instituto de Investigación Biosanitaria de Granada

Rosario Jiménez

Universidad de Granada

Manuel Gómez‐Guzmán

Universidad de Granada

Marta Toral

Instituto de Investigación Biosanitaria de Granada

Francisco Pérez‐Vizcaíno

Universidad Complutense de Madrid

Iñaki Robles‐Vera

Spanish National Centre for Cardiovascular Research

Néstor de la Visitación

Vanderbilt University Medical Center

Júlio Gálvez

Instituto de Investigación Biosanitaria de Granada

Francisco O’Valle

Universidad de Granada

Cooperative Institutions

Universidad de Granada

Hospital Universitari Germans Trias i Pujol

Centro de Investigación en Red en Enfermedades Cardiovasculares

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias

Gestion de l'Eau, Acteurs, Usages

Instituto de Investigación Biosanitaria de Granada

Centro de Investigación Biomédica en Red

Instituto de Salud Carlos III

Universidad Complutense de Madrid

Hospital General Universitario Gregorio Marañón

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Mineralocorticoid receptor blockade improved gut microbiota dysbiosis by reducing gut sympathetic tone in spontaneously hypertensive rats

Biomedicine & Pharmacotherapy (2022)

Cristina González‐Correa Javier Moleón Sofía Miñano Iñaki Robles‐Vera Marta Toral

Microbiota has a crucial role in the host blood pressure (BP) regulation. The present study analyzes whether the mineralocorticoid receptor antagonist spironolactone ameliorates the dysbiosic state in a genetic model of neurogenic hypertension. Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were randomly allocated into three groups: untreated WKY, untreated SHR, and SHR treated with spironolactone for 5 weeks. Spironolactone restored the Firmicutes/Bacteroidetes proportion, and acetate-producing bacteria populations to WKY levels. Spironolactone reduced the percentage of intestinal aerobic bacteria. The amelioration of gut dysbiosis was linked to a reduction in the gut pathology, an enhanced colonic integrity, a reduced gut permeability and an attenuated sympathetic drive in the gut. Spironolactone was unable to reduce neuroinflammation and oxidative stress in the paraventricular nuclei in the hypothalamus. Spironolactone reduced the higher Th17 cells proportion in mesenteric lymph nodes and Th17 infiltration in aorta, improved aortic endothelial function and reduced systolic BP. This study demonstrates for the first time that spironolactone reduces gut dysbiosis in SHR. This effect could be related to its capability to improve gut integrity and pathology due to reduced sympathetic drive in the gut.

Mineralocorticoid

Dysbiosis

10.1016/j.biopha.2022.114149

Cite

Citations (18)

A Diet Supplemented with Husks of Plantago ovata Reduces the Development of Endothelial Dysfunction, Hypertension, and Obesity by Affecting Adiponectin and TNF-α in Obese Zucker Rats

Journal of Nutrition (2005)

Milagros Galisteo Manuel Sánchez Rocío Vera Mercedes González Anna Anguera

Dyslipidemia

Endothelial Dysfunction

Plantago ovata

10.1093/jn/135.10.2399

Cite

Citations (93)

Vascular and Central Activation of Peroxisome Proliferator-Activated Receptor- Attenuates Angiotensin II-Induced Hypertension: Role of RGS-5

Journal of Pharmacology and Experimental Therapeutics (2016)

Miguel Romero Rosario Jiménez Marta Toral Elvira Léon-Gómez Manuel Gómez‐Guzmán

Activation of peroxisome proliferator–activated receptor-β/δ (PPARβ) lowers blood pressure in genetic and mineralocorticoid-induced hypertension. Regulator of G-protein-coupled receptor signaling 5 (RGS5) protein, which interferes in angiotensin II (AngII) signaling, is a target gene to PPARβ. The aim of the present study was to examine whether PPARβ activation in resistance arteries and brain tissues prevents the elevated blood pressure in AngII-induced hypertension and evaluate the role of RGS5 in this effect. C57BL/6J male mice were divided into five groups (control mice, PPARβ agonist [4-[[[2-[3-Fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methylphenoxy]acetic acid (GW0742)-treated mice AngII-infused mice, GW0742-treated AngII-infused mice, and AngII-infused mice treated with GW0742 plus PPARβ antagonist 3-[[[2-Methoxy-4-(phenylamino)phenyl]amino]sulfonyl]-2-thiophenecarboxylic acid methyl ester (GSK0660)) and were followed for 3 weeks. GW0742 prevented the increase in both arterial blood pressure and plasma noradrenaline levels and the higher reduction of blood pressure after ganglionic blockade, whereas it reduced the mesenteric arterial remodeling and the hyper-responsiveness to vasoconstrictors (AngII and endothelin-1) in AngII-infused mice. These effects were accompanied by an inhibition of NADPH oxidase expression and activity in the brain. Gene expression profiling revealed a marked loss of brainstem and vascular RGS5 in AngII-infused mice, which was restored by GW0742. GW0742-induced effects were abolished by GSK0660. Small interfering RNA targeting RGS5 caused augmented contractile response to AngII in resistance mesenteric arteries and blunted the inhibitory effect of GW0742 on this response. In conclusion, GW0742 exerted antihypertensive effects, restoring sympathetic tone and vascular structure and function in AngII-infused mice by PPARβ activation in brain and vessels inhibiting AngII signaling as a result of RGS5 upregulation.

10.1124/jpet.116.233106

Cite

Citations (16)

Identification and Characterization of Novel Angiotensin-Converting Enzyme Inhibitors Obtained from Goat Milk

Journal of Dairy Science (2006)

Arjan Geerlings Inmaculada Concepción Villar F. Hidalgo Zarco Manuel Sánchez Rocío Vera

Captopril

10.3168/jds.s0022-0302(06)72369-4

Cite

Citations (63)

Antihypertensive Effects of Peroxisome Proliferator-Activated Receptor-β Activation in Spontaneously Hypertensive Rats

Hypertension (2011)

María José Zarzuelo Rosario Jiménez Pilar Galindo Manuel Sánchez Ana Nieto

Activation of nuclear hormone receptor peroxisome proliferator-activated receptor β/δ (PPARβ) has been shown to improve insulin resistance and plasma high-density lipoprotein levels, but nothing is known about its effects in genetic hypertension. We studied whether the PPARβ agonist GW0742 might exert antihypertensive effects in spontaneously hypertensive rats (SHRs). The rats were divided into 4 groups, Wistar Kyoto rat-control, Wistar Kyoto rat-treated (GW0742, 5 mg · kg(-1) · day(-1) by oral gavage), SHR-control, and SHR-treated, and followed for 5 weeks. GW0742 induced a progressive reduction in systolic arterial blood pressure and heart rate in SHRs and reduced the mesenteric arterial remodeling, the increased aortic vasoconstriction to angiotensin II, and the endothelial dysfunction characteristic of SHRs. These effects were accompanied by a significant increase in endothelial NO synthase activity attributed to upregulated endothelial NO synthase and downregulated caveolin 1 protein expression. Moreover, GW0742 inhibited vascular superoxide production, downregulated p22(phox) and p47(phox) proteins, decreased both basal and angiotensin II-stimulated NADPH oxidase activity, inhibited extracellular-regulated kinase 1/2 activation, and reduced the expression of the proinflammatory and proatherogenic genes, interleukin 1β, interleukin 6, or intercellular adhesion molecule 1. None of these effects were observed in Wistar Kyoto rats. PPARβ activation, both in vitro and in vivo, increased the expression of the regulators of G protein-coupled signaling proteins RGS4 and RGS5, which negatively modulated the vascular actions of angiotensin II. PPARβ activation exerted antihypertensive effects, restored the vascular structure and function, and reduced the oxidative, proinflammatory, and proatherogenic status of SHRs. We propose PPARβ as a new therapeutic target in hypertension.

Peroxisome proliferator

10.1161/hypertensionaha.111.174490

Cite

Citations (83)

Quercetin inhibits vascular superoxide production induced by endothelin-1: Role of NADPH oxidase, uncoupled eNOS and PKC

Atherosclerosis (2008)

Miguel Romero Rosario Jiménez Manuel Sánchez R López-Sepúlveda María José Zarzuelo

Apocynin

Isorhamnetin

Endothelial Dysfunction

NOX1

10.1016/j.atherosclerosis.2008.03.007

Cite

Citations (136)

SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: Implications for vascular aging

Biochemical Pharmacology (2013)

María José Zarzuelo R López-Sepúlveda Manuel Sánchez Miguel Romero Manuel Gómez‐Guzmán

10.1016/j.bcp.2013.02.015

Cite

Citations (180)

The probiotic Lactobacillus coryniformis CECT5711 reduces the vascular pro-oxidant and pro-inflammatory status in obese mice

Clinical Science (2014)

Marta Toral Manuel Gómez‐Guzmán Rosario Jiménez Miguel Romero Manuel Sánchez

Obesity is associated with intestine dysbiosis and is characterized by a low-grade inflammatory status, which affects vascular function. In the present study, we evaluated the effects of a probiotic with immunomodulatory properties, Lactobacillus coryniformis CECT5711, in obese mice fed on an HFD (high-fat diet). The probiotic treatment was given for 12 weeks, and it did not affect the weight evolution, although it reduced basal glycaemia and insulin resistance. L. coryniformis administration to HFD-induced obese mice induced marked changes in microbiota composition and reduced the metabolic endotoxaemia as it decreased the LPS (lipopolysaccharide) plasma level, which was associated with a significant improvement in gut barrier disruption. Furthermore, it lowered TNFα (tumour necrosis factor α) expression in liver, improving the inflammatory status, and thus the glucose metabolism. Additionally, the probiotic reversed the endothelial dysfunction observed in obese mice when endothelium- and NO (nitric oxide)-dependent vasodilatation induced by acetylcholine in aortic rings was studied. It also restored the increased vessel superoxide levels observed in obese mice, by reducing NADPH oxidase activity and increasing antioxidant enzymes. Moreover, chronic probiotic administration for 2 weeks also improved endothelial dysfunction and vascular oxidative stress induced by in vivo administration of LPS in control mice fed on a standard chow diet. The results of the present study demonstrate an endothelial-protective effect of L. coryniformis CECT5711 in obese mice by increasing NO bioavailability, suggesting the therapeutic potential of this gut microbiota manipulation to prevent vasculopathy in obesity.

Endothelial Dysfunction

Diet-induced obese

10.1042/cs20130339

Cite

Citations (118)

Quercetin Ameliorates Metabolic Syndrome and Improves the Inflammatory Status in Obese Zucker Rats

Obesity (2008)

Leonor Rivera Rocío Morón Manuel Sánchez Antonio Zarzuelo Milagros Galisteo

The aim of this study was to analyze the effects of chronic administration of high doses of quercetin on metabolic syndrome abnormalities, including obesity, dyslipidemia, hypertension, and insulin resistance. For this purpose, obese Zucker rats and their lean littermates were used. The rats received a daily dose of quercetin (2 or 10 mg/kg of body weight) or vehicle for 10 weeks. Body weight and systolic blood pressure (SBP) were recorded weekly. At the end of the treatment, plasma concentrations of triglycerides, total cholesterol, free‐fatty acids (FFAs), glucose, insulin, adiponectin, and nitrate plus nitrite (NOx) were determined. Tumor necrosis factor‐α (TNF‐α) production, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) protein expression were analyzed in visceral adipose tissue (VAT). The raised SBP and high plasma concentrations of triglycerides, total cholesterol, FFA, and insulin found in obese Zucker rats were reduced in obese rats that received either of the doses of quercetin assayed. The higher dose also improved the inflammatory status peculiar to this model, as it increased the plasma concentration of adiponectin, reduced NOx levels in plasma, and lowered VAT TNF‐α production in obese Zucker rats. Furthermore, chronic intake of the higher dose of quercetin enhanced VAT eNOS expression among obese Zucker rats, whereas it downregulated VAT iNOS expression. In conclusion, both doses of quercetin improved dyslipidemia, hypertension, and hyperinsulinemia in obese Zucker rats, but only the high dose produced antiinflammatory effects in VAT together with a reduction in body weight gain.

Hyperinsulinemia

Dyslipidemia

10.1038/oby.2008.315

Cite

Citations (440)

PERSPECTIVA DE GÉNERO EN LA DOCENCIA UNIVERSITARIA:

Dykinson eBooks (2024)

Ana M. Sánchez Claudia Gallego Manuel Sánchez Y. Martín

10.2307/jj.22246998.381

Cite

Citations (0)