{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:12:57Z","timestamp":1787008377799,"version":"build-2736575974"},"reference-count":97,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The present State of the Art Review will take stock of targeting the endocannabinoid system (ECS) in the management of hypertension and vascular diseases. Major efforts have been made in the last thirty years to develop compounds modulating the ECS for diseases, both in the central and peripheral tissues. Agonists of the cannabinoid receptor CB1 elicited hypotension but were at strong risks of inducing tachycardia, heart and kidney damage. The clinical translation of CB2 agonists, as well as antiobesity CB1 blockers, proposed as promising treatments for cardiovascular risk factors, was complicated by adverse side effects. Inhibitors of the membrane enzyme fatty acid amide hydrolase that degrades the endocannabinoid anandamide normalized elevated blood pressure, at least in hypertensive rats. The turning point came when we discovered the phospholipase NAPE-PLD as a systemic target of thiazide diuretics, revealing physicians have indeed targeted the ECS for over sixty years in clinics, unknowingly. The membrane-associated target promotes diuretic effect through its internal channel and generates at the same time anandamide and other lipid signaling amides that exert marked protective actions, useful for the chronic treatment of hypertension. Results have extended our knowledge of the mechanism of thiazide medications, rationalizing both their acute and chronic therapeutic effects. The stabilization of NAPE-PLD by chemical agents that bind to the thiazide-binding site is efficacious in the treatment of hypertension and vascular resistance, providing a validated approach in clinics for the ECS modulation in human diseases associated with neurovascular alterations.<\/jats:p>","DOI":"10.1093\/ajh\/hpaf174","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T11:45:58Z","timestamp":1756381558000},"page":"482-490","source":"Crossref","is-referenced-by-count":2,"title":["State of the Art Review: Thiazide Diuretics Exploit the Endocannabinoid System via NAPE-PLD"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9473-5814","authenticated-orcid":false,"given":"Gianpiero","family":"Garau","sequence":"first","affiliation":[{"name":"Laboratori ALIVEDA, Innovation & Technology Transfer , Pisa ,","place":["Italy"]},{"name":"BioStructures Lab, Istituto Italiano di Tecnologia (IIT@NEST) Piazza San Silvestro 12 , Pisa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"2026031200564439100_CIT0001","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/j.tplants.2020.05.005","article-title":"Phytocannabinoids: origins and biosynthesis","volume":"25","author":"G\u00fclck","year":"2020","journal-title":"Trends Plant Sci"},{"key":"2026031200564439100_CIT0002","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41572-021-00247-4","article-title":"Cannabis use and cannabis use disorder","volume":"7","author":"Connor","year":"2021","journal-title":"Nat Rev Dis Primer"},{"key":"2026031200564439100_CIT0003","doi-asserted-by":"publisher","first-page":"3344","DOI":"10.3390\/ijms23063344","article-title":"Therapeutic use in clinical practice","volume":"23","author":"Pagano","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026031200564439100_CIT0004","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1093\/ajh\/hpad068","article-title":"Trends in cannabis use, blood pressure, and hypertension in middle-aged adults: findings from NHANES, 2009\u20132018","volume":"36","author":"Corroon","year":"2023","journal-title":"Am J Hypertens"},{"key":"2026031200564439100_CIT0005","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/cpt1975183287","article-title":"Cardiovascular effects of prolonged delta-9-tetrahydrocannabinol ingestion","volume":"18","author":"Benowitz","year":"1975","journal-title":"Clin Pharmacol Ther"},{"key":"2026031200564439100_CIT0006","doi-asserted-by":"publisher","first-page":"e93760","DOI":"10.1172\/jci.insight.93760","article-title":"A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study","volume":"2","author":"Jadoon","year":"2017","journal-title":"JCI Insight"},{"key":"2026031200564439100_CIT0007","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1111\/bcp.14225","article-title":"The effects of acute and sustained cannabidiol dosing for seven days on the haemodynamics in healthy men: a randomised controlled trial","volume":"86","author":"Sultan","year":"2020","journal-title":"Br J Clin Pharmacol"},{"key":"2026031200564439100_CIT0008","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/nrd2553","article-title":"Targeting the endocannabinoid system: to enhance or reduce","volume":"7","author":"Di Marzo","year":"2008","journal-title":"Nat Rev Drug Discov"},{"key":"2026031200564439100_CIT0009","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/nrcardio.2017.130","article-title":"Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly","volume":"15","author":"Pacher","year":"2018","journal-title":"Nat Rev Cardiol"},{"key":"2026031200564439100_CIT0010","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1146\/annurev-pharmtox-052220-021800","article-title":"Endocannabinoid-based therapies","volume":"62","author":"Piomelli","year":"2022","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"2026031200564439100_CIT0011","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.chembiol.2025.01.008","article-title":"NAPE-PLD is target of thiazide diuretics","volume":"32","author":"Chiarugi","year":"2025","journal-title":"Cell Chem Biol"},{"key":"2026031200564439100_CIT0012","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.cmet.2013.03.001","article-title":"The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders","volume":"17","author":"Silvestri","year":"2013","journal-title":"Cell Metab"},{"key":"2026031200564439100_CIT0013","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1111\/j.1476-5381.2011.01364.x","article-title":"Endocannabinoid tone versus constitutive activity of cannabinoid receptors","volume":"163","author":"Howlett","year":"2011","journal-title":"Br J Pharmacol"},{"key":"2026031200564439100_CIT0014","doi-asserted-by":"publisher","first-page":"4386","DOI":"10.1111\/bph.15208","article-title":"Cannabinoid control of neurogenic inflammation","volume":"177","author":"McKenna","year":"2020","journal-title":"Br J Pharmacol"},{"key":"2026031200564439100_CIT0015","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.tips.2012.03.002","article-title":"At the heart of the matter: the endocannabinoid system in cardiovascular function and dysfunction","volume":"33","author":"Montecucco","year":"2012","journal-title":"Trends Pharmacol Sci"},{"key":"2026031200564439100_CIT0016","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1172\/JCI119677","article-title":"Production and physiological actions of anandamide in the vasculature of the rat kidney","volume":"100","author":"Deutsch","year":"1997","journal-title":"J Clin Invest"},{"key":"2026031200564439100_CIT0017","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1111\/bph.14168","article-title":"Cannabinoids in arterial, pulmonary and portal hypertension \u2013 mechanisms of action and potential therapeutic significance","volume":"176","author":"Malinowska","year":"2019","journal-title":"Br J Pharmacol"},{"key":"2026031200564439100_CIT0018","doi-asserted-by":"publisher","first-page":"6080","DOI":"10.1038\/s41598-022-09902-6","article-title":"Acute and long-term effects of cannabinoids on hypertension and kidney injury","volume":"12","author":"Golosova","year":"2022","journal-title":"Sci Rep"},{"key":"2026031200564439100_CIT0019","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1161\/01.CIR.0000143230.23252.D2","article-title":"Endocannabinoids acting at Cannabinoid-1 receptors regulate cardiovascular function in hypertension","volume":"110","author":"B\u00e1tkai","year":"2004","journal-title":"Circulation"},{"key":"2026031200564439100_CIT0020","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1016\/S0022-3565(24)36714-X","article-title":"Cannabinoid-induced hypotension and Bradycardia in rats is mediated by CB1-like cannabinoid receptors","volume":"281","author":"Lake","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"2026031200564439100_CIT0021","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/S0140-6736(05)66374-X","article-title":"Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study","volume":"365","author":"Gaal","year":"2005","journal-title":"Lancet"},{"key":"2026031200564439100_CIT0022","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/j.1365-2826.2008.01677.x","article-title":"Endocannabinoids, blood pressure and the human heart","volume":"20","author":"Sarzani","year":"2008","journal-title":"J Neuroendocrinol"},{"key":"2026031200564439100_CIT0023","doi-asserted-by":"publisher","first-page":"e155330","DOI":"10.1172\/JCI155330","article-title":"Do endocannabinoids acting via hepatic CB-1 contribute to NAFLD and hepatic insulin resistance","volume":"132","author":"Kunos","year":"2022","journal-title":"J Clin Invest"},{"key":"2026031200564439100_CIT0024","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.plipres.2011.01.001","article-title":"Is lipid signaling through cannabinoid 2 receptors part of a protective system","volume":"50","author":"Pacher","year":"2011","journal-title":"Prog Lipid Res"},{"key":"2026031200564439100_CIT0025","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1111\/j.1476-5381.2012.02042.x","article-title":"Targeting cannabinoid receptor CB2 in cardiovascular disorders: promises and controversies","volume":"167","author":"Steffens","year":"2012","journal-title":"Br J Pharmacol"},{"key":"2026031200564439100_CIT0026","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/s41569-025-01121-6","article-title":"The relationship between cannabis and cardiovascular disease: clearing the haze","volume":"22","author":"Chandy","year":"2025","journal-title":"Nat Rev Cardiol"},{"key":"2026031200564439100_CIT0027","doi-asserted-by":"publisher","first-page":"e153558","DOI":"10.1172\/JCI153558","article-title":"Nociception and pain in humans lacking a functional TRPV1 channel","volume":"133","author":"Katz","year":"2023","journal-title":"J Clin Invest"},{"key":"2026031200564439100_CIT0028","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3389\/fphar.2015.00006","article-title":"Interactions of the opioid and cannabinoid systems in reward: insights from knockout studies","volume":"6","author":"Katia","year":"2015","journal-title":"Front Pharmacol"},{"key":"2026031200564439100_CIT0029","first-page":"125","article-title":"The opioid system in cardiac and vascular regulation of normal and hypertensive states","volume":"75","author":"Feuerstein","year":"1987","journal-title":"Circulation"},{"key":"2026031200564439100_CIT0030","doi-asserted-by":"publisher","first-page":"16511","DOI":"10.1073\/pnas.0902743106","article-title":"The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo","volume":"106","author":"Whyte","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026031200564439100_CIT0031","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/sj.bjp.0706510","article-title":"Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models","volume":"147","author":"Jayamanne","year":"2006","journal-title":"Br J Pharmacol"},{"key":"2026031200564439100_CIT0032","doi-asserted-by":"publisher","first-page":"3766","DOI":"10.1523\/JNEUROSCI.4071-08.2009","article-title":"Localization of the endocannabinoid-degrading enzyme fatty acid amide hydrolase in rat dorsal root ganglion cells and its regulation after peripheral nerve injury","volume":"29","author":"Lever","year":"2009","journal-title":"J Neurosci"},{"key":"2026031200564439100_CIT0033","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1038\/nn.2632","article-title":"Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism","volume":"13","author":"Clapper","year":"2010","journal-title":"Nat Neurosci"},{"key":"2026031200564439100_CIT0034","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/j.1527-3458.2006.00021.x","article-title":"Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597)","volume":"12","author":"Piomelli","year":"2006","journal-title":"CNS Drug Rev"},{"key":"2026031200564439100_CIT0035","doi-asserted-by":"publisher","first-page":"1911572","DOI":"10.1080\/19490976.2021.1911572","article-title":"At the heart of microbial conversations: endocannabinoids and the microbiome in cardiometabolic risk","volume":"13","author":"Khan","year":"2021","journal-title":"Gut Microbes"},{"key":"2026031200564439100_CIT0036","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1124\/pr.58.3.2","article-title":"The endocannabinoid system as an emerging target of pharmacotherapy","volume":"58","author":"Pacher","year":"2006","journal-title":"Pharmacol Rev"},{"key":"2026031200564439100_CIT0037","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1016\/j.chembiol.2010.08.013","article-title":"Inhibitor of fatty acid amide hydrolase normalizes cardiovascular function in hypertension without adverse metabolic effects","volume":"17","author":"Godlewski","year":"2010","journal-title":"Chem Biol"},{"key":"2026031200564439100_CIT0038","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.neuropharm.2004.12.005","article-title":"Blood pressure regulation by endocannabinoids and their receptors","volume":"48","author":"Pacher","year":"2005","journal-title":"Neuropharmacology"},{"key":"2026031200564439100_CIT0039","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1021\/ja308733u","article-title":"A binding site for nonsteroidal anti-inflammatory drugs in fatty acid amide hydrolase","volume":"135","author":"Bertolacci","year":"2013","journal-title":"J Am Chem Soc"},{"key":"2026031200564439100_CIT0040","doi-asserted-by":"publisher","first-page":"551","DOI":"10.3390\/cells14070551","article-title":"FAAH modulators from natural sources: a collection of new potential drugs","volume":"14","author":"Nicoara","year":"2025","journal-title":"Cells"},{"key":"2026031200564439100_CIT0041","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/cpt.2290","article-title":"Safety, tolerability, and pharmacokinetics of FAAH inhibitor BIA 10-2474: a double-blind, randomized, placebo-controlled study in healthy volunteers","volume":"111","author":"Rocha","year":"2022","journal-title":"Clin Pharmacol Ther"},{"key":"2026031200564439100_CIT0042","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.neuropharm.2017.06.015","article-title":"The cannabinoid system and pain","volume":"124","author":"Woodhams","year":"2017","journal-title":"Neuropharmacology"},{"key":"2026031200564439100_CIT0043","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1038\/ajh.2008.198","article-title":"A human fatty acid amide hydrolase (FAAH) functional gene variant is associated with lower blood pressure in young males","volume":"21","author":"Sarzani","year":"2008","journal-title":"Am J Hypertens"},{"key":"2026031200564439100_CIT0044","doi-asserted-by":"publisher","first-page":"6395","DOI":"10.1038\/ncomms7395","article-title":"FAAH genetic variation enhances fronto-amygdala function in mouse and human","volume":"6","author":"Dincheva","year":"2015","journal-title":"Nat Commun"},{"key":"2026031200564439100_CIT0045","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.bbalip.2016.03.003","article-title":"Lipidomics profile of a NAPE-PLD KO mouse provides evidence of a broader role of this enzyme in lipid metabolism in the brain","volume":"1861","author":"Leishman","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"2026031200564439100_CIT0046","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1042\/BJ20041790","article-title":"Mammalian cells stably overexpressing N -acylphosphatidylethanolamine-hydrolysing phospholipase D exhibit significantly decreased levels of N -acylphosphatidylethanolamines","volume":"389","author":"Okamoto","year":"2005","journal-title":"Biochem J"},{"key":"2026031200564439100_CIT0047","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0009-3084(00)00192-4","article-title":"N-Acylethanolamines and precursor phospholipids \u2014 relation to cell injury","volume":"108","author":"Hansen","year":"2000","journal-title":"Chem Phys Lipids"},{"key":"2026031200564439100_CIT0048","doi-asserted-by":"publisher","first-page":"2559","DOI":"10.1016\/S0006-3495(97)78899-4","article-title":"N-acylphosphatidylethanolamines: effect of the N-acyl chain length on its orientation","volume":"72","author":"Lafrance","year":"1997","journal-title":"Biophys J"},{"key":"2026031200564439100_CIT0049","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.bbamem.2005.07.004","article-title":"N-acyl phosphatidylethanolamines affect the lateral distribution of cholesterol in membranes","volume":"1715","author":"T\u00e9rov\u00e1","year":"2005","journal-title":"Biochim Biophys Acta"},{"key":"2026031200564439100_CIT0050","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41421-020-00233-2","article-title":"Plasma membrane integrity in health and disease: significance and therapeutic potential","volume":"7","author":"Dias","year":"2021","journal-title":"Cell Discov"},{"key":"2026031200564439100_CIT0051","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/S0895-7061(02)03257-0","article-title":"Membrane fluidity and hypertension","volume":"16","author":"Tsuda","year":"2003","journal-title":"Am J Hypertens"},{"key":"2026031200564439100_CIT0052","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1038\/oby.2010.219","article-title":"A common haplotype in NAPEPLD is associated with severe obesity in a norwegian population-based cohort (the HUNT study)","volume":"19","author":"Wangensteen","year":"2011","journal-title":"Obesity"},{"key":"2026031200564439100_CIT0053","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1111\/j.1750-3639.2011.00477.x","article-title":"Cannabinoid receptor and N-acyl phosphatidylethanolamine phospholipase D\u2014evidence for altered expression in multiple sclerosis","volume":"21","author":"Zhang","year":"2011","journal-title":"Brain Pathol"},{"key":"2026031200564439100_CIT0054","doi-asserted-by":"publisher","first-page":"5818","DOI":"10.1038\/s41598-018-23938-7","article-title":"Canine NAPEPLD-associated models of human myelin disorders","volume":"8","author":"Minor","year":"2018","journal-title":"Sci Rep"},{"key":"2026031200564439100_CIT0055","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.str.2014.12.018","article-title":"Structure of human N -acylphosphatidylethanolamine-hydrolyzing phospholipase D: regulation of fatty acid ethanolamide biosynthesis by bile acids","volume":"23","author":"Magotti","year":"2015","journal-title":"Structure"},{"key":"2026031200564439100_CIT0056","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.3390\/cells12131752","article-title":"Origin, diversity, and multiple roles of enzymes with metallo-\u03b2-lactamase fold from different organisms","volume":"12","author":"Diene","year":"2023","journal-title":"Cells"},{"key":"2026031200564439100_CIT0057","doi-asserted-by":"publisher","first-page":"2908","DOI":"10.1021\/acschembio.6b00624","article-title":"Bile acid recognition by NAPE-PLD","volume":"11","author":"Margheritis","year":"2016","journal-title":"ACS Chem Biol"},{"key":"2026031200564439100_CIT0058","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41574-019-0266-7","article-title":"Bile acids in glucose metabolism and insulin signalling \u2014 mechanisms and research needs","volume":"15","author":"Ahmad","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"2026031200564439100_CIT0059","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.3390\/cells9051247","article-title":"Hepatic NAPE-PLD is a key regulator of liver lipid metabolism","volume":"9","author":"Lefort","year":"2020","journal-title":"Cells"},{"key":"2026031200564439100_CIT0060","doi-asserted-by":"publisher","first-page":"6495","DOI":"10.1038\/ncomms7495","article-title":"Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota","volume":"6","author":"Geurts","year":"2015","journal-title":"Nat Commun"},{"key":"2026031200564439100_CIT0061","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41467-018-08051-7","article-title":"Intestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis","volume":"10","author":"Everard","year":"2019","journal-title":"Nat Commun"},{"key":"2026031200564439100_CIT0062","doi-asserted-by":"publisher","first-page":"15927","DOI":"10.1038\/s41598-019-51799-1","article-title":"A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-OHDA-induced neurodegeneration","volume":"9","author":"Palese","year":"2019","journal-title":"Sci Rep"},{"key":"2026031200564439100_CIT0063","doi-asserted-by":"publisher","first-page":"12814","DOI":"10.1039\/C7CC07582K","article-title":"Synthesis and characterization of the first inhibitor of N -acylphosphatidylethanolamine phospholipase D (NAPE-PLD)","volume":"53","author":"Castellani","year":"2017","journal-title":"Chem Commun"},{"key":"2026031200564439100_CIT0064","doi-asserted-by":"publisher","first-page":"7289","DOI":"10.1074\/jbc.RA120.013362","article-title":"Symmetrically substituted dichlorophenes inhibit N-acyl-phosphatidylethanolamine phospholipase D","volume":"295","author":"Aggarwal","year":"2020","journal-title":"J Biol Chem"},{"key":"2026031200564439100_CIT0065","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1021\/acschembio.3c00401","article-title":"Small molecule activation of NAPE-PLD enhances efferocytosis by macrophages","volume":"18","author":"Zarrow","year":"2023","journal-title":"ACS Chem Biol"},{"key":"2026031200564439100_CIT0066","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/s41589-020-0528-7","article-title":"Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice","volume":"16","author":"Mock","year":"2020","journal-title":"Nat Chem Biol"},{"key":"2026031200564439100_CIT0067","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1161\/HYPERTENSIONAHA.109.129171","article-title":"Thiazide effects and adverse effects: insights from molecular genetics","volume":"54","author":"Ellison","year":"2009","journal-title":"Hypertension"},{"key":"2026031200564439100_CIT0068","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1152\/physrev.2000.80.1.211","article-title":"Sodium-potassium-chloride cotransport","volume":"80","author":"Russell","year":"2000","journal-title":"Physiol Rev"},{"key":"2026031200564439100_CIT0069","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1172\/JCI111420","article-title":"A thiazide-sensitive, electrically neutral transport system","volume":"74","author":"Stokes","year":"1984","journal-title":"J Clin Invest"},{"key":"2026031200564439100_CIT0070","doi-asserted-by":"publisher","first-page":"7006","DOI":"10.1038\/s41467-024-51381-y","article-title":"Structural bases for Na+-Cl\u2212 cotransporter inhibition by thiazide diuretic drugs and activation by kinases","volume":"15","author":"Zhao","year":"2024","journal-title":"Nat Commun"},{"key":"2026031200564439100_CIT0071","doi-asserted-by":"publisher","first-page":"815","DOI":"10.3389\/fphar.2019.00815","article-title":"Mechanism of thiazide diuretic arterial pressure reduction: the search continues","volume":"10","author":"Rapoport","year":"2019","journal-title":"Front Pharmacol"},{"key":"2026031200564439100_CIT0072","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41392-023-01527-z","article-title":"Structure of human NCC: insights into the inhibition mechanism of thiazides","volume":"8","author":"De Souza Goncalves","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"2026031200564439100_CIT0073","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1097\/HJH.0000000000002088","article-title":"Redefining diuretics use in hypertension: why select a thiazide-like diuretic","volume":"37","author":"Burnier","year":"2019","journal-title":"J Hypertens"},{"key":"2026031200564439100_CIT0074","doi-asserted-by":"publisher","first-page":"2707","DOI":"10.1111\/bcp.14109","article-title":"A review of the prescribing trend of thiazide-type and thiazide-like diuretics in hypertension: a UK perspective","volume":"85","author":"McNally","year":"2019","journal-title":"Br J Clin Pharmacol"},{"key":"2026031200564439100_CIT0075","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.13589","article-title":"Hypertension survey finds many US adults lack key knowledge of the condition","author":"Anderer","year":"2025","journal-title":"JAMA"},{"key":"2026031200564439100_CIT0076","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1093\/ajh\/hpac048","article-title":"Thiazide and the thiazide-like diuretics: review of hydrochlorothiazide, chlorthalidone, and indapamide","volume":"35","author":"Ernst","year":"2022","journal-title":"Am J Hypertens"},{"key":"2026031200564439100_CIT0077","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.2174\/1389200219666180702104559","article-title":"Thiazide therapy in chronic kidney disease: renal and extra renal targets","volume":"19","author":"Pourafshar","year":"2018","journal-title":"Curr Drug Metab"},{"key":"2026031200564439100_CIT0078","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1001\/jamainternmed.2019.7454","article-title":"Comparison of cardiovascular and safety outcomes of chlorthalidone vs hydrochlorothiazide to treat hypertension","volume":"180","author":"Hripcsak","year":"2020","journal-title":"JAMA Intern Med"},{"key":"2026031200564439100_CIT0079","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1056\/NEJMoa2212270","article-title":"Chlorthalidone vs. hydrochlorothiazide for hypertension\u2013cardiovascular events","volume":"387","author":"Ishani","year":"2022","journal-title":"N Engl J Med"},{"key":"2026031200564439100_CIT0080","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1016\/S0140-6736(24)01744-6","article-title":"Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial","volume":"404","author":"Rodgers","year":"2024","journal-title":"Lancet"},{"key":"2026031200564439100_CIT0081","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1111\/j.1476-5381.2011.01747.x","article-title":"Triphasic blood pressure responses to cannabinoids: do we understand the mechanism","volume":"165","author":"Malinowska","year":"2012","journal-title":"Br J Pharmacol"},{"key":"2026031200564439100_CIT0082","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1093\/ajh\/hpaa195","article-title":"Mechanisms of vascular remodeling in hypertension","volume":"34","author":"Humphrey","year":"2021","journal-title":"Am J Hypertens"},{"key":"2026031200564439100_CIT0083","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1111\/j.1476-5381.2008.00034.x","article-title":"Acute hypertension reveals depressor and vasodilator effects of cannabinoids in conscious rats","volume":"156","author":"Ho","year":"2009","journal-title":"Br J Pharmacol"},{"key":"2026031200564439100_CIT0084","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1161\/01.HYP.0000051641.58674.F7","article-title":"Anandamide-induced depressor effect in spontaneously hypertensive rats: role of the vanilloid receptor","volume":"41","author":"Li","year":"2003","journal-title":"Hypertension"},{"key":"2026031200564439100_CIT0085","doi-asserted-by":"publisher","first-page":"H476","DOI":"10.1152\/ajpheart.00975.2010","article-title":"Large-conductance Ca2+ -activated K+ channel \u03b21 -subunit knockout mice are not hypertensive","volume":"300","author":"Xu","year":"2011","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026031200564439100_CIT0086","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/sj.bjp.0704333","article-title":"Mechanisms of anandamide-induced vasorelaxation in rat isolated coronary arteries","volume":"134","author":"White","year":"2001","journal-title":"Br J Pharmacol"},{"key":"2026031200564439100_CIT0087","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1080\/19336950.2016.1273997","article-title":"T-type Ca2+ channels and autoregulation of local blood flow","volume":"11","author":"Jensen","year":"2017","journal-title":"Channels"},{"key":"2026031200564439100_CIT0088","doi-asserted-by":"publisher","first-page":"4141","DOI":"10.1111\/febs.15446","article-title":"Enzymes, pseudoenzymes, and moonlighting proteins: diversity of function in protein superfamilies","volume":"287","author":"Jeffery","year":"2020","journal-title":"FEBS J"},{"key":"2026031200564439100_CIT0089","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1002\/jimd.12060","article-title":"Disorders affecting vitamin B6 metabolism","volume":"42","author":"Wilson","year":"2019","journal-title":"J Inherit Metab Dis"},{"key":"2026031200564439100_CIT0090","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/nrn1174","article-title":"The biochemistry of neuronal necrosis: rogue biology","volume":"4","author":"Syntichaki","year":"2003","journal-title":"Nat Rev Neurosci"},{"key":"2026031200564439100_CIT0091","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.3390\/nu11071484","article-title":"Dietary vitamin B6 intake associated with a decreased risk of cardiovascular disease: a prospective cohort study","volume":"11","author":"Jeon","year":"2019","journal-title":"Nutrients"},{"key":"2026031200564439100_CIT0092","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1111\/joim.20015","article-title":"Pyridoxal-5\u2032-phosphate: A cost-effective treatment candidate for hypertensive patients","volume":"296","author":"Lellig","year":"2024","journal-title":"J Intern Med"},{"key":"2026031200564439100_CIT0093","doi-asserted-by":"publisher","first-page":"e2250621","DOI":"10.1001\/jamanetworkopen.2022.50621","article-title":"Folate, vitamin B6, and vitamin B12 status in association with metabolic syndrome incidence","volume":"6","author":"Zhu","year":"2023","journal-title":"JAMA Netw Open"},{"key":"2026031200564439100_CIT0094","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-024-53673-9","article-title":"Exposing 24-hour cycles in bile acids of male humans","volume":"15","author":"Bello","year":"2024","journal-title":"Nature Communications"},{"key":"2026031200564439100_CIT0095","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1124\/jpet.123.001665","article-title":"Role of Cannabinoid Signaling in Cardiovascular Function and Ischemic Injury","volume":"387","author":"Rorabaugh","year":"2023","journal-title":"The Journal of Pharmacology and Experimental Therapeutics"},{"key":"2026031200564439100_CIT0096","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1161\/HYPERTENSIONAHA.122.18085","article-title":"Hypertension, neurovascular dysfunction, and cognitive impairment","volume":"80","author":"Santisteban","year":"2023","journal-title":"Hypertension"},{"key":"2026031200564439100_CIT0097","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1093\/ajh\/hpae007","article-title":"Hypertension and Mild Cognitive Impairment: State-of-the-Art Review","volume":"37","author":"Shajahan","year":"2024","journal-title":"American Journal of Hypertension"}],"container-title":["American Journal of Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajh\/advance-article-pdf\/doi\/10.1093\/ajh\/hpaf174\/64195353\/hpaf174.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajh\/article-pdf\/39\/4\/482\/64195353\/hpaf174.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajh\/article-pdf\/39\/4\/482\/64195353\/hpaf174.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:56:48Z","timestamp":1773291408000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajh\/article\/39\/4\/482\/8246171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":97,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,9,1]]},"published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ajh\/hpaf174","relation":{},"ISSN":["0895-7061","1941-7225"],"issn-type":[{"value":"0895-7061","type":"print"},{"value":"1941-7225","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2025,9,1]]}}}