Renal and cardiovascular sensory receptors and blood pressure regulation

Abstract

Studies over the past decade have highlighted important roles played by sensory receptors outside of traditionally sensory tissues; for example, taste receptors participate in pH sensing in the cerebrospinal fluid, bitter taste receptors mediate bronchodilation and ciliary beating in the lung (Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB. Nat Med 16: 1299-1304, 2010; Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ. Science 325: 1131-1134, 2009), and olfactory receptors play roles in both sperm chemotaxis and muscle cell migration (Griffin CA, Kafadar KA, Pavlath GK. Cell 17: 649-661, 2009). More recently, several studies have shown that sensory receptors also play important roles in the regulation of blood pressure. This review will focus on several recent studies examining the roles that sensory receptors play in blood pressure regulation, with an emphasis on three pathways: the adenylate cyclase 3 (AC3) pathway, the Gpr91-succinate signaling pathway, and the Olfr78/Gpr41 short-chain fatty acid signaling pathway. Together, these pathways demonstrate that sensory receptors play important roles in mediating blood pressure control and that blood pressure regulation is coupled to the metabolism of the host as well as the metabolism of the gut microbiota.

Keywords: Gpr91; Olfr78; olfactory receptors; short-chain fatty acids; succinate.

Fig. 1.

Working model for the acute hypotensive effect of short-chain fatty acid (SCFA) delivery on blood pressure (BP, blood pressure; WT, wild type; KO, knockout). Gpr41 acts to decrease blood pressure in response to SCFA, whereas Olfr78 acts in opposition to increase blood pressure. In WT animals, the hypotensive response of Gpr41 prevails. When Olfr78 is genetically deleted, the hypotensive response is further accentuated as the “brake” on the pathway has been removed. However, when Gpr41 is genetically deleted, the hypotensive response is absent, and instead a slight hypertensive response (presumably mediated by Olfr78) remains.

Fig. 2.

When WT mice are treated with antibiotics (ABX) to reduce gut flora and therefore the circulating SCFA, the Olfr78 and Gpr41 sides of the pathway are eliminated simultaneously, and therefore there is little change in blood pressure. However, in mice null for Olfr78, SCFA are signaling solely through the hypotensive side of the pathway. Therefore, if the ligand is reduced by antibiotic treatment in these mice, this hypotensive pathway is disrupted and there is a relative increase in blood pressure.