Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics

Expert Rev Cardiovasc Ther. 2010 Jun;8(6):793-802. doi: 10.1586/erc.10.27.


Thiazide and thiazide-like diuretics are among the most commonly used antihypertensives and have been available for over 50 years. However, the mechanism by which these drugs chronically lower blood pressure is poorly understood. Possible mechanisms include direct endothelial- or vascular smooth muscle-mediated vasodilation and indirect compensation to acute decreases in cardiac output. In addition, thiazides are associated with adverse metabolic effects, particularly hyperglycemia, and the mechanistic underpinnings of these effects are also poorly understood. Thiazide-induced hypokalemia, as well as other theories to explain these metabolic disturbances, including increased visceral adiposity, hyperuricemia, decreased glucose metabolism and pancreatic beta-cell hyperpolarization, may play a role. Understanding genetic variants with differential responses to thiazides could reveal new mechanistic candidates for future research to provide a more complete understanding of the blood pressure and metabolic response to thiazide diuretics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / adverse effects*
  • Antihypertensive Agents / pharmacokinetics
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Biotransformation / genetics
  • Blood Pressure / drug effects*
  • Cardiac Output / drug effects
  • Humans
  • Hypertension / drug therapy*
  • Metabolic Syndrome / chemically induced
  • Potassium / metabolism
  • Risk Factors
  • Sodium Chloride Symporter Inhibitors / adverse effects*
  • Sodium Chloride Symporter Inhibitors / pharmacokinetics
  • Sodium Chloride Symporter Inhibitors / pharmacology*
  • Sodium Chloride Symporter Inhibitors / therapeutic use
  • Sodium Chloride Symporters / genetics
  • Sodium Chloride Symporters / physiology
  • Vasodilation / drug effects


  • Antihypertensive Agents
  • Sodium Chloride Symporter Inhibitors
  • Sodium Chloride Symporters
  • Potassium