Role of Ca2+-activated K+ channels in the protective effect of ACE inhibition against ischemic myocardial injury.

Abstract

Angiotensin-converting enzyme (ACE) inhibitors increase the production of nitric oxide (NO) and prostacyclin and open Ca2+-activated K+ channels. The effects of these actions of ACE inhibitors on infarct size were investigated in open-chest dogs subjected to myocardial ischemia and reperfusion. Infarct size was assessed 6 hours after the onset of reperfusion, subsequent to 90 minutes of occlusion of the left anterior descending coronary artery. The ACE inhibitor cilazaprilat was administered into the coronary artery 10 minutes before coronary occlusion, and infusion was continued until 1 hour after reperfusion. The bradykinin and NO concentrations in coronary venous blood 10 minutes after the onset of reperfusion were significantly higher in dogs treated with cilazaprilat (3 microg x kg(-1) x min(-1)) than in control animals. Although there were no significant differences in collateral flow during ischemia, infarct size in the cilazaprilat group was smaller than that in the control group (15.1+/-3.0% versus 46.7+/-4.2% of the area at risk, P<0.0001). The infarct size-limiting effect of cilazaprilat was partially reduced by either N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase) or iberiotoxin (a blocker of Ca2+-activated K+ channels) and was abolished by N(G)-nitro-L-arginine methyl ester plus iberiotoxin. Indomethacin (an inhibitor of cyclooxygenase) had no effect on the beneficial action of cilazaprilat. Inhibition of ACE thus reduced myocardial infarct size, an effect that was mediated by NO and the opening of Ca2+-activated K+ channels in canine hearts.

• Authors: K Node, M Kitakaze, H Kosaka, T Minamino, H Mori, M Hori
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 31 Issue 6 Pg. 1290-8 (Jun 1998) ISSN: 0194-911X [Print] United States
• PMID: 9622144 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Enzyme Inhibitors
• Peptides
• Potassium Channels
• Scorpion Venoms
• Toxins, Biological
• Cilazapril
• Nitric Oxide
• iberiotoxin
• Epoprostenol
• Nitric Oxide Synthase
• Bradykinin
• Calcium
• NG-Nitroarginine Methyl Ester
• cilazaprilat

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Bradykinin (blood)
• Calcium (metabolism)
• Cilazapril (analogs & derivatives, pharmacology)
• Collateral Circulation
• Coronary Circulation
• Data Interpretation, Statistical
• Dogs
• Enzyme Inhibitors (pharmacology)
• Epoprostenol (physiology)
• Myocardial Infarction (pathology, physiopathology, prevention & control)
• Myocardial Reperfusion Injury
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (blood, physiology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Peptides (pharmacology)
• Potassium Channels (drug effects, physiology)
• Scorpion Venoms (pharmacology)
• Time Factors
• Toxins, Biological (pharmacology)