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Cited by 448Gut microbiota and healthBlood Pressure and Hypertension StudiesNitric Oxide and Endothelin Effects

Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41

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Natarajan, Niranjana, Hori, Daijiro, Flavahan, Sheila, Steppan, Jochen, Flavahan, Nicholas A., Berkowitz, Dan E., Pluznick, Jennifer L.·2016·Physiological Genomics
DOI 10.1152/physiolgenomics.00089.2016PMC PMC6223570
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Abstract

Short chain fatty acid (SCFA) metabolites are byproducts of gut microbial metabolism that are known to affect host physiology via host G protein-coupled receptor (GPCRs). We previously showed that an acute SCFA bolus decreases blood pressure (BP) in anesthetized mice, an effect mediated primarily via Gpr41. In this study, our aims were to identify the cellular localization of Gpr41 and to determine its role in BP regulation. We localized Gpr41 to the vascular endothelium using RT-PCR: Gpr41 is detected in intact vessels (with endothelium) but is absent from denuded vessels (without endothelium). Furthermore, using pressure myography we confirmed that SCFAs dilate resistance vessels in an endothelium-dependent manner. Since we previously found that Gpr41 mediates a hypotensive response to acute SCFA administration, we hypothesized that Gpr41 knockout (KO) mice would be hypertensive. Here, we report that Gpr41 KO mice have isolated systolic hypertension compared with wild-type (WT) mice; diastolic BP was not different between WT and KO. Older Gpr41 KO mice also exhibited elevated pulse wave velocity, consistent with a phenotype of systolic hypertension; however, there was no increase in ex vivo aorta stiffness (measured by mechanical tensile testing). Plasma renin concentrations were also similar in KO and WT mice. The systolic hypertension in Gpr41 KO is not salt sensitive, as it is not significantly altered on either a high- or low-salt diet. In sum, these studies suggest that endothelial Gpr41 lowers baseline BP, likely by decreasing active vascular tone without altering passive characteristics of the blood vessels, and that Gpr41 KO mice have hypertension of a vascular origin.

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  • Olfr78 and Gpr41 participate in host blood pressure regulation.

    “Early mechanistic studies by Pluznick and colleagues substantiated this idea by demonstrating the G-protein coupled SCFA receptors olfactory receptor 78 (Olfr78) and G-protein receptor 41 (Gpr41) participate in host blood pressure regulation59–61.”

    From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [61]

  • Interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects in animal models and in patients with hypertension.

    “Finally, studies in animal models and in patients with hypertension have reported that interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects87,92–99.”

    From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [94]

  • Administration of propionate modulates blood pressure in mice, likely via binding to G protein-coupled receptor 41 and olfactory receptor 78.

    “Administration of propionate has also been reported to modulate blood pressure in mice, likely via binding to the G protein-coupled receptor 41 (GPR41) and olfactory receptor 78 (OLFR78; also known as OR51E2)93,94.”

    From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [94]

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  1. [37]Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly YM, Glickman JN, Garrett WS. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science (New York, NY) : 569–573, 2013. [DOI] [PMC free article] [PubMed] [Google Scholar]

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Authors
Natarajan, N., Hori, D., Flavahan, S., Steppan, J., Flavahan, N. A., Berkowitz, D. E., & Pluznick, J. L.
Affiliations
Johns Hopkins University (US)
Corresponding author
Pluznick, Jennifer L.
ORCID
Venue
Physiological Genomics
Publisher
American Physiological Society
Published
2016-11-01
Volume
48
Issue
11
Pages
826-834
ISSN
  • 1094-8341 (ISSN-L)
  • 1531-2267
DOI
10.1152/physiolgenomics.00089.2016
PMC
PMC6223570
OpenAlex
W2522093042
Cited by
441
References
47
Citations by year
2026: 37 · 2025: 50 · 2024: 42 · 2023: 52 · 2022: 67 · 2021: 68 · 2020: 51 · 2019: 32 · 2018: 26 · 2017: 16
FWCI
12.82
Type
journal article
Language
en
Open access
Locations
  • Physiological Genomics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association (AHA) (14PRE20090006, 16IRG27260265)
  • Japan Heart foundation
  • HHS | National Institutes of Health (NIH) (R01HL12851, NIH R01DK107726)
  • Hopkins Conte Digestive Diseases Basic and Traslational Research Core Center
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
short-chain fatty acids, GPR41, blood pressure regulation, systolic hypertension, gut microbiota, endothelium-dependent vasodilation, pulse wave velocity, aortic stiffness, plasma renin, salt sensitivity
MeSH terms
Animals, Bacteria, Blood Pressure, Endothelium, Vascular, Fatty Acids, Volatile, Female, Hypertension, Male, Mice, Inbred C57BL, Renin, Systole, Vasodilation, Sodium Chloride, Dietary, Mice, Knockout, Sus scrofa, Receptors, G-Protein-Coupled, Metabolome

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