ArticleCirculation2016
Conditional Deletion of Hsd11b2 in the Brain Causes Salt Appetite and Hypertension.
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Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41citing papers in PubMed
8.9field-weighted citation impact, top 2% of its field
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41 citing papers in PubMed, 72 citations in OpenAlex.
- Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with KInternational journal of molecular sciences · 2026Article
- Evidence of 11β-hydroxysteroid Dehydrogenase Type 2 Protein Expression and Enzymatic Activity in the Adult Rat Brain.Neuromolecular medicine · 2026Article
- Science with Seymour Levine: on glucocorticoid action from birth to senescence.Neurobiology of stress · 2026Article
- Chronic ACTH Infusion Alters the Diurnal Rhythm of Sodium Excretion, Inducing Nondipping Blood Pressure and Salt-Sensitivity in Male Mice.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Serum Cortisol and Cardiovascular Disease Risk - A Potential Biomarker.Current cardiology reviews · 2025Review
- Notoginsenoside R1 Improved Hypoxic Pulmonary Hypertension by Inhibiting Glycolysis-Mediated Pulmonary Arterial Vascular Remodeling.Canadian respiratory journal · 2025Article
- Removing interoceptive input from the kidney to the brain reduces salt appetite in DOCA hypertensive rats.Kidney international · 2024Article
- Control of sodium appetite by hindbrain aldosterone-sensitive neurons.Molecular and cellular endocrinology · 2024Review
- Modifying Dietary Sodium and Potassium Intake: An End to the 'Salt Wars'?Hypertension (Dallas, Tex. : 1979) · 2024Review
- Coping with the multifaceted and multifunctional role of cortisol in the brain.Neuroscience applied · 2024Review
- Glucocorticoids with or without fludrocortisone in septic shock: a narrative review from a biochemical and molecular perspective.British journal of anaesthesia · 2024Review
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Sodium Intake and Disease: Another Relationship to Consider.Nutrients · 2023Review
- Apparent mineralocorticoid excess: comprehensive overview of molecular genetics.Journal of translational medicine · 2022Review
- Genetic Modifications to Alter Blood Pressure Level.Biomedicines · 2022Review
- The impact of excessive salt intake on human health.Nature reviews. Nephrology · 2022Review
- Central regulation of body fluid homeostasis.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2022Review
- Alteration of the gut microbiota and metabolite phenylacetylglutamine in patients with severe chronic heart failure.Frontiers in cardiovascular medicine · 2022Article
- Abnormal neonatal sodium handling in skin precedes hypertension in the SAME rat.Pflugers Archiv : European journal of physiology · 2021Article
- Decreased 11β-Hydroxysteroid Dehydrogenase Type 2 Expression in the Kidney May Contribute to Nicotine/Smoking-Induced Blood Pressure Elevation in Mice.Hypertension (Dallas, Tex. : 1979) · 2021Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Louise C EvansFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Jessica R IvyFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Caitlin WyrwollFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Julie A McNairnFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Robert I MenziesFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Thorbjørn H ChristensenFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Emad A S Al-DujailiFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Christopher J KenyonFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
John J MullinsFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Jonathan R SecklFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Megan C HolmesFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense.
Matthew A BaileyFrom British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, United Kingdom (L.C.E., J.R.I., C.W., J.A.M., R.I.M., T.H.C., C.J.K., J.J.M., J.R.S., M.C.H., M.A.B.); and Dietetics, Nutrition and Biological Sciences Department, Queen Margaret University, Edinburgh, United Kingdom (E.A.S.Al-D.). The current address for Dr Evans is Department of Physiology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee; the current address for Dr Wyrwoll is School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, Australia; and the current address for Dr Christensen is Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense. Matthew.Bailey@ed.ac.uk.
University of Western Australia · AUBritish Heart Foundation · GBMedical College of Wisconsin · USQueen Margaret University · GB
Funding
British Heart Foundation FS/07/063/24075British Heart Foundation FS/11/78/29328British Heart Foundation FS/15/60/31510British Heart Foundation RE/08/001Wellcome Trust 079009
Abstract
backgroundThe hypertensive syndrome of Apparent Mineralocorticoid Excess is caused by loss-of-function mutations in the gene encoding 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), allowing inappropriate activation of the mineralocorticoid receptor by endogenous glucocorticoid. Hypertension is attributed to sodium retention in the distal nephron, but 11βHSD2 is also expressed in the brain. However, the central contribution to Apparent Mineralocorticoid Excess and other hypertensive states is often overlooked and is unresolved. We therefore used a Cre-Lox strategy to generate 11βHSD2 brain-specific knockout (Hsd11b2.BKO) mice, measuring blood pressure and salt appetite in adults. METHODS AND
resultsBasal blood pressure, electrolytes, and circulating corticosteroids were unaffected in Hsd11b2.BKO mice. When offered saline to drink, Hsd11b2.BKO mice consumed 3 times more sodium than controls and became hypertensive. Salt appetite was inhibited by spironolactone. Control mice fed the same daily sodium intake remained normotensive, showing the intrinsic salt resistance of the background strain. Dexamethasone suppressed endogenous glucocorticoid and abolished the salt-induced blood pressure differential between genotypes. Salt sensitivity in Hsd11b2.BKO mice was not caused by impaired renal sodium excretion or volume expansion; pressor responses to phenylephrine were enhanced and baroreflexes impaired in these animals.
conclusionsReduced 11βHSD2 activity in the brain does not intrinsically cause hypertension, but it promotes a hunger for salt and a transition from salt resistance to salt sensitivity. Our data suggest that 11βHSD2-positive neurons integrate salt appetite and the blood pressure response to dietary sodium through a mineralocorticoid receptor-dependent pathway. Therefore, central mineralocorticoid receptor antagonism could increase compliance to low-sodium regimens and help blood pressure management in cardiovascular disease.
Indexed as
11-beta-Hydroxysteroid Dehydrogenase Type 2AnimalsBaroreflexCorticosteroneCravingDexamethasoneDrinking BehaviorGenes, SyntheticHypertensionMiceMice, Inbred C57BLMice, KnockoutMineralocorticoid Excess Syndrome, ApparentMineralocorticoid Receptor AntagonistsNephronsNerve Tissue Proteins11-beta-Hydroxysteroid Dehydrogenase Type 2CorticosteroneDexamethasoneHSD11B2 protein, mouseMineralocorticoid Receptor AntagonistsNerve Tissue ProteinsNes protein, ratNestinPotassiumReceptors, MineralocorticoidRNA, MessengerSodium Chloride, DietarySpironolactonealdosteronemineralocorticoidspressoreceptorssaltsolitary nucleus
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