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The Microbiome and Blood Pressure:?Can Microbes Regulate Our Blood Pressure?

ABSTRACT: The surfaces of the human body are heavily populated by a highly diverse microbial ecosystem termed the microbiota. The largest and richest among these highly heterogeneous populations of microbes is the gut microbiota. The collection of microbes and their genes, called the microbiome, has been studied intensely through the past few years using novel metagenomics, metatranscriptomics, and metabolomics approaches. This has enhanced our understanding of how the microbiome affects our metabolic, immunologic, neurologic, and endocrine homeostasis. Hypertension is a leading cause of cardiovascular disease worldwide; it contributes to stroke, heart disease, kidney failure, premature death, and disability. Recently, studies in humans and animals have shown that alterations in microbiota and its metabolites are associated with hypertension and atherosclerosis. In this review, we compile the recent findings and hypotheses describing the interplay between the microbiome and blood pressure, and we highlight some prospects by which utilization of microbiome-related techniques may be incorporated to better understand the pathophysiology and treatment of hypertension.

SUBMITTER: Al Khodor S

PROVIDER: S-EPMC5474689 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The Microbiome and Blood Pressure: Can Microbes Regulate Our Blood Pressure?

Al Khodor Souhaila S Reichert Bernd B Shatat Ibrahim F IF

Frontiers in pediatrics 20170619

The surfaces of the human body are heavily populated by a highly diverse microbial ecosystem termed the microbiota. The largest and richest among these highly heterogeneous populations of microbes is the gut microbiota. The collection of microbes and their genes, called the microbiome, has been studied intensely through the past few years using novel metagenomics, metatranscriptomics, and metabolomics approaches. This has enhanced our understanding of how the microbiome affects our metabolic, im ...[more]

PMID: 28674682

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Project description:BackgroundCurrent paradigms suggest that nitric oxide (NO) produced by endothelial cells (ECs) through endothelial nitric oxide synthase (eNOS) in the vessel wall is the primary regulator of blood flow and blood pressure. However, red blood cells (RBCs) also carry a catalytically active eNOS, but its role is controversial and remains undefined. This study aimed to elucidate the functional significance of RBC eNOS compared with EC eNOS for vascular hemodynamics and nitric oxide metabolism.MethodsWe generated tissue-specific loss- and gain-of-function models for eNOS by using cell-specific Cre-induced gene inactivation or reactivation. We created 2 founder lines carrying a floxed eNOS (eNOSflox/flox) for Cre-inducible knockout (KO), and gene construct with an inactivated floxed/inverted exon (eNOSinv/inv) for a Cre-inducible knock-in (KI), which respectively allow targeted deletion or reactivation of eNOS in erythroid cells (RBC eNOS KO or RBC eNOS KI mice) or in ECs (EC eNOS KO or EC eNOS KI mice). Vascular function, hemodynamics, and nitric oxide metabolism were compared ex vivo and in vivo.ResultsThe EC eNOS KOs exhibited significantly impaired aortic dilatory responses to acetylcholine, loss of flow-mediated dilation, and increased systolic and diastolic blood pressure. RBC eNOS KO mice showed no alterations in acetylcholine-mediated dilation or flow-mediated dilation but were hypertensive. Treatment with the nitric oxide synthase inhibitor Nγ-nitro-l-arginine methyl ester further increased blood pressure in RBC eNOS KOs, demonstrating that eNOS in both ECs and RBCs contributes to blood pressure regulation. Although both EC eNOS KOs and RBC eNOS KOs had lower plasma nitrite and nitrate concentrations, the levels of bound NO in RBCs were lower in RBC eNOS KOs than in EC eNOS KOs. Reactivation of eNOS in ECs or RBCs rescues the hypertensive phenotype of the eNOSinv/inv mice, whereas the levels of bound NO were restored only in RBC eNOS KI mice.ConclusionsThese data reveal that eNOS in ECs and RBCs contribute independently to blood pressure homeostasis.

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The Microbiome and Blood Pressure:?Can Microbes Regulate Our Blood Pressure?

Publications

The Microbiome and Blood Pressure: Can Microbes Regulate Our Blood Pressure?

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