This Article Free upon publication Full Text Full Text (PDF) All Versions of this Article: 54/2/196    most recent HYPERTENSIONAHA.109.129171v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Ellison, D. H. Articles by Loffing, J. PubMed PubMed Citation Articles by Ellison, D. H. Articles by Loffing, J. Related Collections Cardiovascular Pharmacology Genetically altered mice Genomics Hypertension - basic studies Ion channels/membrane transport Genetics of cardiovascular disease Endothelium/vascular type/nitric oxide

(Hypertension. 2009;54:196.)
© 2009 American Heart Association, Inc.

Brief Reviews

Thiazide Effects and Adverse Effects

Insights From Molecular Genetics

From the Division of Nephrology and Hypertension (D.H.E.), Department of Physiology and Pharmacology (D.H.E.), Oregon Health & Science University, Portland, Ore; Department of Veterans’ Affairs (D.H.E.), Portland, Ore; Institute of Anatomy (J.L.), University of Zurich, Zurich, Switzerland.

Correspondence to David H. Ellison, Division of Nephrology and Hypertension, Oregon Health & Science University, 3314 SW US Veterans Hospital Rd, Portland, OR 97239. E-mail ellisond@ohsu.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
One of the longest-running debates in clinical medicine shows no sign of disappearing; just when it seems that thiazides have reassumed their role as front-line drugs to treat hypertension,¹ new concerns emerge,^2–4 leading some to question their role once again.⁵ Thiazides are effective antihypertensives with long track records and low cost. The major concerns about their use arise from their tendency to cause hypokalemia, impair glucose tolerance, increase serum cholesterol, and increase serum uric acid. Few medical controversies have generated as much heat, with well-established camps staking out positions that appear resistant to change.^6–9 The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, the largest study of antihypertensive monotherapy ever performed,¹⁰ was intended to identify the best first-line treatment for high-risk hypertensive individuals; however, despite its size and the numerous resulting publications, its implications and authority continue to be disputed. The goal of this review is not take sides in this debate but rather to inject a distinct, and sometimes neglected, perspective; during the past 15 years, remarkable developments in molecular biology and human genetics have provided substantial insights into the pathogenesis of hypertension and mechanisms and adverse effects of diuretics. Diuretic proponents and antagonists alike often neglect these developments when addressing the topic; it is the purpose of this Brief Review to integrate these developments into the debate with the goal of generating questions that can be addressed scientifically.

	How Thiazides Reduce Blood Pressure

 
Thiazide diuretics were developed during the 1950s, when chemists and physiologists at Merck Sharpe and Dohme tested derivatives of . . . [Full Text of this Article]