ATP-sensitive K+ channel openers: old drugs with new clinical benefits for the heart.

Abstract

Different types of ATP-sensitive K+ (K(ATP)) channels have been identified in cardiomyocytes, vascular smooth muscle cells, pancreatic beta-cells, neurons and mitochondria. Years before the discovery of the K(ATP) channel in cardiomyocytes, pharmacological openers of this channel had been developed for the treatment of angina pectoris and hypertension. The K(ATP) channel plays an important role not only in coronary blood flow regulation but also in protection of cardiovascular cells from ischemia/reperfusion injury. In animal models of myocardial ischemia/reperfusion, activation of the mitochondrial K(ATP) channels by their pharmacological openers has been shown to attenuate endothelial dysfunction and to reduce myocardial necrosis. Conversely, blockade of the K(ATP) channel aggravates microvascular necrosis and the no-reflow phenomenon after ischemia/reperfusion, resulting in augmentation of post-infarct ventricular dysfunction. Recent clinical studies have shown that a combination of coronary reperfusion therapy and infusion of nicorandil, a hybrid of K(ATP) channel opener and nitrate, improved left ventricular function in patients with acute myocardial infarction. Furthermore, chronic treatment with nicorandil has been shown to significantly improve prognosis of patients with high-risk stable angina pectoris. Both of these clinical benefits cannot be attributed to the nitrate property of nicorandil. However, a recent basic investigation has suggested that the protective function of K(ATP) channel openers is compromised by concurrent hypercholesterolemia and administration of sulfonylureas for diabetes mellitus. These interferences in the beneficial action of K(ATP) channel openers by concurrent illness and pharmacological agents need to be further investigated to allow a more effective use of K(ATP) channel openers in patients with coronary artery diseases.

• Authors: Tetsuji Miura, Takayuki Miki
• Journal: Current vascular pharmacology (Curr Vasc Pharmacol) Vol. 1 Issue 3 Pg. 251-8 (Oct 2003) ISSN: 1570-1611 [Print] United Arab Emirates
• PMID: 15320472 (Publication Type: Journal Article, Review)

Chemical References

• Potassium Channel Blockers
• Potassium Channels
• Vasodilator Agents
• Nicorandil
• Pinacidil
• Adenosine Triphosphate
• Diazoxide
• Glyburide

Topics

• Adenosine Triphosphate (physiology)
• Animals
• Coronary Circulation (physiology)
• Coronary Disease (drug therapy, physiopathology)
• Diazoxide (pharmacology, therapeutic use)
• Glyburide (pharmacology, therapeutic use)
• Humans
• Ion Channel Gating (drug effects)
• Myocardial Reperfusion Injury (physiopathology, prevention & control)
• Nicorandil (pharmacology, therapeutic use)
• Pinacidil (pharmacology, therapeutic use)
• Potassium Channel Blockers (pharmacology, therapeutic use)
• Potassium Channels (drug effects, physiology)
• Randomized Controlled Trials as Topic
• Vasodilator Agents (pharmacology, therapeutic use)