Short chain fatty acid metabolites lower blood pressure via endothelial Gpr41

Abstract

Short chain fatty acid (SCFA) metabolites, which are produced by gut microbial metabolism, affect various aspects of host physiology. We previously reported that propionate (an SCFA) induces an acute hypotensive response via the G-protein coupled receptor Gpr41, and that Gpr41 is expressed in the vasculature. However, the cellular localization of Gpr41 within blood vessels, and the chronic effect of Gpr41 on blood pressure (BP) was unknown. Therefore, we used RT-PCR of murine vessels either with or without intact endothelium (endo) to show that although b-actin is detected in both vessel types, Gpr41 (and eNOS) are only detected in vessels with intact endo. Because Gpr41 was found to mediate a hypotensive response to SCFAs, we hypothesized that Gpr41 knockout (KO) mice would be hypertensive at baseline. In accordance with our hypothesis, our data indicates that KO mice (n=5) have systolic hypertension compared to wild-type (WT, n=3) mice (day 3 of baseline, dark cycle: WT 119±3, KO 130±1 mmHg, light cycle: WT 111±4, KO 120±2 mmHg; p<0.05) as well as elevated pulse pressures (dark cycle: WT 23±1, KO 37±3 mmHg, light cycle: WT 23±2, KO 34±3; p<0.01). We hypothesize that endothelial Gpr41 mediates a chronic hypotensive influence on BP, and are currently pursuing the hypothesis that this effect is mediated via eNOS.