Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics.
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.
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0486, USA.
Julio D
JD
Duarte
Rhonda M
RM
Cooper-DeHoff
D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001711:Biotransformation / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D024821:Metabolic Syndrome / Q000139:chemically induced; D011188:Potassium / Q000378:metabolism; D012307:Risk Factors; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D049992:Sodium Chloride Symporters / Q000235:genetics / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D049993:Sodium Chloride Symporter Inhibitors; D049992:Sodium Chloride Symporters; D011188:Potassium