TY - JOUR
T1 - Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41
AU - Natarajan, Niranjana
AU - Hori, Daijiro
AU - Flavahan, Sheila
AU - Steppan, Jochen
AU - Flavahan, Nicholas A.
AU - Berkowitz, Dan E.
AU - Pluznick, Jennifer L.
N1 - Funding Information:
This work was supported by the American Heart Association (Predoctoral Fellowship to N. Natarajan, 16IRG27260265 to J. L. Pluznick), the National Institutes of Health (R01DK-107726 and R01HL-128512 to J. L. Pluznick) and Japan Heart Association (D. Hori).
Publisher Copyright:
© 2016 the American Physiological Society.
PY - 2016/11/14
Y1 - 2016/11/14
N2 - Short chain fatty acid (SCFA) metabolites are byproducts of gut microbial metabolism that are known to affect host physiology via host G proteincoupled 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.
AB - Short chain fatty acid (SCFA) metabolites are byproducts of gut microbial metabolism that are known to affect host physiology via host G proteincoupled 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.
KW - Acetate
KW - Endothelium
KW - GPCR
KW - Hypertension
KW - Microbiota
KW - Propionate
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U2 - 10.1152/physiolgenomics.00089.2016
DO - 10.1152/physiolgenomics.00089.2016
M3 - Article
C2 - 27664183
AN - SCOPUS:84995579577
VL - 48
SP - 826
EP - 834
JO - Physiological Genomics
JF - Physiological Genomics
SN - 1094-8341
IS - 11
ER -