Nitric oxide synthase uncoupling: a therapeutic target in cardiovascular diseases.

Abstract

Nitric oxide synthase enzyme (NOS) possesses the unique ability to be "uncoupled" to produce superoxide anion (O(2)(-)) instead of nitric oxide (NO). Reduced NO bioavailability as a result of NOS uncoupling has been speculated to play an essential role in cardiovascular pathologies including dilated cardiomyopathy, ischemia reperfusion injury, endothelial dysfunction, atherosclerosis, hypertension and diabetes mellitus. NO serves many important roles in the heart including stimulation of adenylate cyclase (AC) at low levels or guanalyl cyclase (sGC) at higher levels, or by s-nitrosylation of intracellular Ca(2+) regulatory proteins thus altering excitation-contraction coupling. Not surprisingly, NOS uncoupling is an emerging therapeutic target in cardiovascular diseases. Restoring proper NOS activity by increasing intracellular levels of its cofactor tetrahydrobiopterin (BH4) is effective in the management of hypertensive diastolic dysfunction, ischemia-reperfusion injury, myocardial infarction and endothelial dysfunction. New evidence is constantly emerging highlighting the importance of NOS uncoupling in cardiovascular pathologies thus the purpose of this mini-review is to showcase the new advances and promising treatments for NOS uncoupling in CV disease.

• Authors: Nathan D Roe, Jun Ren
• Journal: Vascular pharmacology (Vascul Pharmacol) 2012 Nov-Dec Vol. 57 Issue 5-6 Pg. 168-72 ISSN: 1879-3649 [Electronic] United States
• PMID: 22361333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cardiovascular Agents
• Nitric Oxide
• Arginine
• Nitric Oxide Synthase
• Calcium

Topics

• Animals
• Arginine (metabolism)
• Calcium (metabolism)
• Cardiovascular Agents (pharmacology, therapeutic use)
• Cardiovascular Diseases (drug therapy, physiopathology)
• Humans
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (drug effects, metabolism)
• Oxidative Stress