title: Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.
abstract: Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response.
authors.affiliation: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Shahin
authors.affiliation: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA. Electronic address: johnson@cop.ufl.edu.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D004232:Diuretics / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D049971:Thiazides / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D049971:Thiazides