Smelling through calcium‐sensing receptor affects sympathetic control of blood pressure and regional blood flow

Abstract

T. 2018. Aromatherapy: Activating olfactory calcium-sensing receptors impairs renal hemodynamics via sympathetic nerve-mediated vasoconstriction. Acta Pysiol. 225, e13157. A number of G-protein-coupled "orphan" receptors with no known ligand have been identified in both olfactory epithelium and the kidney (for review see ref. 1) and some of them contribute to the regulation of kidney function and blood pressure. 2 In the present issue of Acta Physiologica, a G-protein-coupled receptor with known ligand, the calcium-sensing receptor, CaSR, that is expressed abundantly in kidney and parathyroid, is now documented also in the nasal olfactory epithelium of rat, and moreover, its activation shown to initiate sympathetic efferent nerve activity to increase blood pressure and decrease perfusion of the renal, hepatic, and enteric vascular beds. 3 The findings show a direct coupling between activation of the CaSR in the olfactory epithelium and increased peripheral vascular resistance by sympathetic excitation. The relevance for human vs rodent physiology, needs to be established. Moreover, concentration-response curves, the fluid-borne vs normal airborne delivery of ligand and neuroanatomical correlates need to be further explored. The reflex coupling is novel and intriguing and warrants further study of the role for nasal olfactory epithelium in blood pressure homoeostasis.In the study published in Acta, 3 Lee et al couple elegantly previous observations of manganese inhalation in mine workers causing elevated blood pressure and renal injury and that zebrafish larvae express CaSR in nasal epithelium into a mechanistic physiologic hypothesis predicting that activation of CaSR in the nasal epithelium may activate efferent sympathetic vascular nerves and thereby impact blood pressure. To test the hypothesis, they employ a rat model whereby the nasal cavity under anaesthesia is gently flushed and potential extracellular ligands-both agonists and antagonists-are delivered to the olfactory epithelium. Several control experiments were performed to assure specificity of the response. As to the sensory part, olfactory receptors comprise a large group of G-proteincoupled receptors in mammals that are expressed in the nasal olfactory epithelium and detect volatile molecules in smell but with more widespread expression across organs. As an example, the olfactory receptor Olfr78 is an oxygen sensor in the carotid body which is sensitive to the metabolite lactate and thereby controls respiration. 4 However, Olfr78, which is sensitive also to short-chain fatty acids as endogenous ligand, is also expressed in the kidney, notably in the juxtaglomerular granular cells that synthesize and release the protease renin into plasma and thereby controls activity of the circulating renin-angiotensin-aldosterone system. Olfr78 stimulation by short-chain fatty acids decreases renin secretion and, in vivo, plasma renin concentration was lower in mice stimulated by short-chain fatty acids. 2

The Calcilytic Drug Calhex-231 Ameliorates Vascular Hyporesponsiveness in Traumatic Hemorrhagic Shock by Inhibiting Oxidative Stress and miR-208a-Mediated Mitochondrial Fission

“…In the cardiovascular system, functional CaSR is present in cardiomyocytes, perivascular nerves, vascular endothelial cells (VECs), and vascular smooth muscle cells (VSMCs) [8]. Some studies have shown that CaSR plays an important role in the regulation of vascular tone and blood pressure [7][8][9][10]. However, the precise functional mechanism of CaSR in the cardiovascular system has not yet been fully clarified.…”

The calcilytic drug Calhex-231 ameliorates vascular hyporesponsiveness in traumatic hemorrhagic shock by inhibiting oxidative stress and mitochondrial fission

“…In the cardiovascular system, functional CaSR is present in cardiomyocytes, perivascular nerves, vascular endothelial cells (VECs), and vascular smooth muscle cells (VSMCs) [9]. Several studies have shown that CaSR plays an important role in the regulation of vascular tone and blood pressure [8][9][10][11]. However, the precise mechanism by which CaSR regulates blood pressure has not been determined.…”

Recent advances in blood pressure research

“…Given the enormous complexity of olfactory input to the brain, it is difficult to translate single findings to general conclusions with regard to blood pressure regulation. Thus, there is still some way to go to establish beneficial therapeutic effects of smelling specific volatile compounds, but a potential link between olfactory G‐protein‐coupled receptors and cardiovascular control is now established in a rat model as was stated by Boye L. Jensen in a recent contribution related to that topic …”