Olfactory receptor 78 modulates renin but not baseline blood pressure

Abstract

Olfactory receptors (ORs) are the largest family of Gprotein coupled receptors (GPCRs), with nearly 350 genes in humans (Malnic et al., 2004) and nearly 1000 genes in mice (Godfrey et al., 2004). While they were initially characterized as specialized chemosensors in the nose, ORs are also expressed in a wide range of tissues where they play functional roles (Griffin et al., 2009;Spehr et al., 2003), including in the kidney (Pluznick et al., 2009). Although most murine ORs do not have a clear human ortholog, Olfactory receptor 78 (Olfr78) is one of only three murine genes to have a clear ortholog across 13 placental mammals, including humans (Niimura et al., 2014). In a prior study, we reported that Olfr78 localizes to both vascular smooth muscle cells and to the juxtaglomerular apparatus (JGA) of the kidney, where it plays a role in renin release (Pluznick et al., 2013). Both Olfr78 and its human ortholog OR51E2 respond to the short chain fatty acids (SCFAs) acetate and propionate

How Dietary Fibre, Acting via the Gut Microbiome, Lowers Blood Pressure

“…Due to the lack of OLFR78, the renin response was abolished and, thus, an acute drop in BP was observed, confirming that OLFR78 raised BP and antagonized the hypotensive effects of propionate [ 52 •]. In a recent study, OLFR78 was investigated in chronic BP regulation, showing that Olfr78 −/− mice had lower renin levels but no differences in baseline BP compared to their WT counterparts [ 61 ].…”

Reduced intestinal butyrate availability is associated with the vascular remodeling in resistance arteries of hypertensive rats

“…Olfr78 role in hypertension was characterized primarily in the renal afferent arterioles, where it was related to the release of renin after stimulus with propionate ( Pluznick et al, 2013 ; Poll et al, 2021 ). Since it is a receptor coupled to a Gs protein and expressed in the VSMCs ( Pluznick et al, 2013 ; Poll et al, 2020 ; Mermer et al, 2021 ), its local activation may likely be related to vascular muscle relaxation in the presence of acetate or propionate.…”

The role of the gut microbiota in health and cardiovascular diseases

“…Olfr78 can participate in the activation of the sympathetic nerve, the formation of hypertension and the increase in carotid body activity [ 318 ]. Besides, the plasma renin activity in Olfr78-KO mice was lower than that in wild type mice, which may be induced by high levels of SCFAs activation [ 317 , 320 ]. In short, gut microbiota may play a crucial role in the regulation of hypertension through SCFAs-mediated mechanisms, and SCFAs have the potential to be a therapeutic target for hypertension.…”