Short chain fatty acid (SCFA) metabolites are byproducts of gut microbial metabolism that are known to affect host physiology via GPCRs. We previously showed that an acute SCFA bolus decreases blood pressure (BP) in anesthetized mice, an effect mediated 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, but is absent from denuded vessels. 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 knockout (KO) mice have isolated systolic hypertension compared to 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 electromechanical tensile testing). Plasma renin concentration was 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.
- Copyright © 2016, Physiological Genomics