Changes in Gut Microbiota Induced by Doxycycline Influence in Vascular Function and Development of Hypertension in DOCA-Salt Rats

被引:17
作者
Robles-Vera, Inaki [1 ,2 ]
de la Visitacion, Nestor [1 ,2 ]
Toral, Marta [3 ,4 ]
Sanchez, Manuel [1 ,2 ,5 ]
Romero, Miguel [1 ,2 ,5 ]
Gomez-Guzman, Manuel [1 ,2 ,5 ]
Vargas, Felix [5 ,6 ]
Duarte, Juan [1 ,2 ,4 ,5 ]
Jimenez, Rosario [1 ,2 ,4 ,5 ]
机构
[1] Univ Granada, Sch Pharm, Dept Pharmacol, Granada 18071, Spain
[2] Univ Granada, Ctr Biomed Res CIBM, Granada 18071, Spain
[3] Ctr Nacl Invest Cardiovasc CNI, Gene Regulat Cardiovasc Remodeling & Inflamma Grp, Madrid 28029, Spain
[4] CIBERCV, Madrid 28029, Spain
[5] Inst Invest Biosanitaria Granada, Granada 18012, Spain
[6] Univ Granada, Sch Med, Dept Physiol, Granada 18071, Spain
关键词
doxycycline; gut dysbiosis; hypertension; oxidative stress; inflammation; DOCA-salt model; NADPH OXIDASE ACTIVITY; BLOOD-PRESSURE; ENDOTHELIAL DYSFUNCTION; OXIDATIVE STRESS; RECEPTOR; ANTIBIOTICS; ACTIVATION; DYSBIOSIS; PROTECTS; PREVENT;
D O I
10.3390/nu13092971
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Previous experiments in animals and humans show that shifts in microbiota and its metabolites are linked to hypertension. The present study investigates whether doxycycline (DOX, a broad-spectrum tetracycline antibiotic) improves dysbiosis, prevent cardiovascular pathology and attenuate hypertension in deoxycorticosterone acetate (DOCA)-salt rats, a renin-independent model of hypertension. Male Wistar rats were randomly assigned to three groups: control, DOCA-salt hypertensive rats, DOCA-salt treated with DOX for 4 weeks. DOX decreased systolic blood pressure, improving endothelial dysfunction and reducing aortic oxidative stress and inflammation. DOX decreased lactate-producing bacterial population and plasma lactate levels, improved gut barrier integrity, normalized endotoxemia, plasma noradrenaline levels and restored the Treg content in aorta. These data demonstrate that DOX through direct effects on gut microbiota and its non-microbial effects (anti-inflammatory and immunomodulatory) reduces endothelial dysfunction and the increase in blood pressure in this low-renin form of hypertension.
引用
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页数:17
相关论文
共 59 条
[21]   A new therapeutic association to manage relapsing experimental colitis: Doxycycline plus Saccharomyces boulardii [J].
Garrido-Mesa, Jose ;
Algieri, Francesca ;
Rodriguez-Nogales, Alba ;
Pilar Utrilla, Ma ;
Elena Rodriguez-Cabezas, Ma ;
Zarzuelo, Antonio ;
Angeles Ocete, Ma ;
Garrido-Mesa, Natividad ;
Galvez, Julio .
PHARMACOLOGICAL RESEARCH, 2015, 97 :48-63
[22]   Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats [J].
Gomez-Guzman, Manuel ;
Toral, Marta ;
Romero, Miguel ;
Jimenez, Rosario ;
Galindo, Pilar ;
Sanchez, Manuel ;
Jose Zarzuelo, Maria ;
Olivares, Monica ;
Galvez, Julio ;
Duarte, Juan .
MOLECULAR NUTRITION & FOOD RESEARCH, 2015, 59 (11) :2326-2336
[23]   Epicatechin lowers blood pressure, restores endothelial function, and decreases oxidative stress and endothelin-1 and NADPH oxidase activity in DOCA-salt hypertension [J].
Gomez-Guzman, Manuel ;
Jimenez, Rosario ;
Sanchez, Manuel ;
Jose Zarzuelo, Maria ;
Galindo, Pilar ;
Maria Quintela, Ana ;
Lopez-Sepulveda, Rocio ;
Romero, Miguel ;
Tamargo, Juan ;
Vargas, Felix ;
Perez-Vizcaino, Francisco ;
Duarte, Juan .
FREE RADICAL BIOLOGY AND MEDICINE, 2012, 52 (01) :70-79
[24]   Link between microbiota and hypertension: Focus on LPS/TLR4 pathway in endothelial dysfunction and vascular inflammation, and therapeutic implication of probiotics [J].
Grylls, Alina ;
Seidler, Karin ;
Neil, James .
BIOMEDICINE & PHARMACOTHERAPY, 2021, 137
[25]   Doxycycline Dose-dependently Inhibits MMP-2-Mediated Vascular Changes in 2K1C Hypertension [J].
Guimaraes, Danielle A. ;
Rizzi, Elen ;
Ceron, Carla S. ;
Oliveira, Alisson M. ;
Oliveira, Diogo M. ;
Castro, Michele M. ;
Tirapelli, Carlos R. ;
Gerlach, Raquel F. ;
Tanus-Santos, Jose E. .
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 2011, 108 (05) :318-325
[26]   IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation [J].
Gunnett, CA ;
Heistad, DD ;
Berg, DJ ;
Faraci, FM .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2000, 279 (04) :H1555-H1562
[27]   Interleukin-17 causes Rho-kinase-mediated endothelial dysfunction and hypertension [J].
Hoanglan Nguyen ;
Chiasson, Valorie L. ;
Chatterjee, Piyali ;
Kopriva, Shelley E. ;
Young, Kristina J. ;
Mitchell, Brett M. .
CARDIOVASCULAR RESEARCH, 2013, 97 (04) :696-+
[28]   Historical perspective: gut dysbiosis and hypertension [J].
Honour, John William .
PHYSIOLOGICAL GENOMICS, 2015, 47 (10) :443-446
[29]  
HONOUR JW, 1985, J ENDOCRINOL, V105, P347, DOI 10.1677/joe.0.1050347
[30]   Doxycycline protects human intestinal cells from hypoxia/reoxygenation injury: Implications from an in-vitro hypoxia model [J].
Hummitzsch, Lars ;
Zitta, Karina ;
Berndt, Rouven ;
Kott, Matthias ;
Schildhauer, Christin ;
Parczany, Kerstin ;
Steinfath, Markus ;
Albrecht, Martin .
EXPERIMENTAL CELL RESEARCH, 2017, 353 (02) :109-114