TY - JOUR
T1 - Olfactory receptor 78 modulates renin but not baseline blood pressure
AU - Poll, Brian G.
AU - Xu, Jiaojiao
AU - Gupta, Kunal
AU - Shubitowski, Tyler B.
AU - Pluznick, Jennifer L.
N1 - Funding Information:
This work was supported by the National Institutes of Health National Heart Lung and Blood Institute [F31HL144061 to BP, R01HL128512 to JLP]; and National Institute for Diabetes and Digestive and Kidney Diseases [R01DK107726 to JLP]. This work was published in a modified form as part of a doctoral dissertation under embargo for four years: Poll, B. G. (2020). "Exploring Microbiome-Host Interactions: Elucidating the effects of Short-Chain Fatty Acids and Olfactory Receptor 78 on Hemodynamics and Renal Function" [Doctoral dissertation, Johns Hopkins University School of Medicine, Baltimore].
Funding Information:
This work was supported by the National Institutes of Health National Heart Lung and Blood Institute [F31HL144061 to BP, R01HL128512 to JLP]; and National Institute for Diabetes and Digestive and Kidney Diseases [R01DK107726 to JLP].
Publisher Copyright:
© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society
PY - 2021/9
Y1 - 2021/9
N2 - Olfactory receptor 78 (Olfr78) is a G protein-coupled receptor (GPCR) that is expressed in the juxtaglomerular apparatus (JGA) of the kidney as well as the peripheral vasculature, and is activated by gut microbial metabolites. We previously reported that Olfr78 plays a role in renin secretion in isolated glomeruli, and that Olfr78 knockout (KO) mice have lower plasma renin activity. We also noted that in anesthetized mice, Olfr78KO appeared to be hypotensive. In this study, we used radiotelemetry to determine the role of Olfr78 in chronic blood pressure regulation. We found that the blood pressure of Olfr78KO mice is not significantly different than that of their WT counterparts at baseline, or on high- or low-salt diets. However, Olfr78KO mice have depressed heart rates on high-salt diets. We also report that Olfr78KO mice have lower renin protein levels associated with glomeruli. Finally, we developed a mouse where Olfr78 was selectively knocked out in the JGA, which phenocopied the lower renin association findings. In sum, these experiments suggest that Olfr78 modulates renin, but does not play an active role in blood pressure regulation at baseline, and is more likely activated by high levels of short chain fatty acids or hypotensive events. This study provides important context to our knowledge of Olfr78 in BP regulation.
AB - Olfactory receptor 78 (Olfr78) is a G protein-coupled receptor (GPCR) that is expressed in the juxtaglomerular apparatus (JGA) of the kidney as well as the peripheral vasculature, and is activated by gut microbial metabolites. We previously reported that Olfr78 plays a role in renin secretion in isolated glomeruli, and that Olfr78 knockout (KO) mice have lower plasma renin activity. We also noted that in anesthetized mice, Olfr78KO appeared to be hypotensive. In this study, we used radiotelemetry to determine the role of Olfr78 in chronic blood pressure regulation. We found that the blood pressure of Olfr78KO mice is not significantly different than that of their WT counterparts at baseline, or on high- or low-salt diets. However, Olfr78KO mice have depressed heart rates on high-salt diets. We also report that Olfr78KO mice have lower renin protein levels associated with glomeruli. Finally, we developed a mouse where Olfr78 was selectively knocked out in the JGA, which phenocopied the lower renin association findings. In sum, these experiments suggest that Olfr78 modulates renin, but does not play an active role in blood pressure regulation at baseline, and is more likely activated by high levels of short chain fatty acids or hypotensive events. This study provides important context to our knowledge of Olfr78 in BP regulation.
KW - blood pressure
KW - olfactory receptors
KW - renin
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U2 - 10.14814/phy2.15017
DO - 10.14814/phy2.15017
M3 - Article
C2 - 34549531
AN - SCOPUS:85115796466
SN - 2051-817X
VL - 9
JO - Physiological Reports
JF - Physiological Reports
IS - 18
M1 - e15017
ER -