47
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

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

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Author and article information

          Journal
          Physiol Genomics
          Physiol. Genomics
          physiolgenomics
          physiolgenomics
          physiolgenomics
          Physiological Genomics
          American Physiological Society (Bethesda, MD )
          1094-8341
          1531-2267
          23 September 2016
          1 November 2016
          1 November 2017
          : 48
          : 11
          : 826-834
          Affiliations
          [1] 1Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland; and
          [2] 2Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland
          Author notes
          Address for reprint requests and other correspondence: J. L. Pluznick, 725 No. Wolfe St., WBSB 205, Baltimore, MD 21205 (e-mail: jpluznick@ 123456jhmi.edu ).
          Article
          PMC6223570 PMC6223570 6223570 PG-00089-2016
          10.1152/physiolgenomics.00089.2016
          6223570
          27664183
          f46a2716-addb-4a4a-a5de-6a3d408220b7
          Copyright © 2016 the American Physiological Society
          History
          : 27 July 2016
          : 19 September 2016
          Funding
          Funded by: American Heart Association (AHA)
          Award ID: 14PRE20090006
          Award ID: 16IRG27260265
          Funded by: Japan Heart foundation
          Funded by: HHS | National Institutes of Health (NIH)
          Award ID: R01HL12851
          Award ID: NIH R01DK107726
          Funded by: Hopkins Conte Digestive Diseases Basic and Traslational Research Core Center
          Categories
          Call for Papers
          Research-Article
          Gut Microbiota in Health and Disease

          acetate,microbiota,hypertension,GPCR,endothelium,propionate
          acetate, microbiota, hypertension, GPCR, endothelium, propionate

          Comments

          Comment on this article