Blockade of angiotensin II type 1 receptors suppressed free radical production and preserved coronary endothelial function in the rabbit heart after myocardial infarction.

Abstract

The hypothesis that blockade of angiotensin II type 1 (AT1) receptors after myocardial infarction prevents coronary endothelial vasomotor dysfunction by suppressing oxygen free radical production was examined. Rabbits underwent coronary ligation or a sham operation with or without infusion of valsartan, an AT 1 receptor blocker. Two weeks after the operation, the heart was isolated from each rabbit and perfused with buffer in the Langendorff mode, and coronary flow responses to acetylcholine and sodium nitroprusside were assessed. The ratio of heart weight to body weight and the lipid peroxide level in the myocardium were increased by 30 and 50%, respectively, 2 weeks after infarction. The coronary flow response to acetylcholine (10(-8) to 10(-5) M) was reduced by 50% in the hearts with infarction compared with the sham controls, although coronary flow responses to sodium nitroprusside were similar. The coronary flow response to acetylcholine in the hearts with infarction was restored by concurrent infusion of N -2-mercaptopropionyl-glycine, a free radical scavenger. Valsartan (10 mg/kg/d) infused after infarction prevented both ventricular remodeling and elevation of the tissue lipid peroxide level and preserved coronary flow response to acetylcholine. In conclusion, long-term AT1 receptor blockade after infarction protects the coronary arteries from endothelial vasomotor dysfunction through suppression of free radical production.

• Authors: Atsushi Kuno, Tetsuji Miura, Akihito Tsuchida, Tohru Hasegawa, Takayuki Miki, Yasuhiro Nishino, Kazuaki Shimamoto
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 39 Issue 1 Pg. 49-57 (Jan 2002) ISSN: 0160-2446 [Print] United States
• PMID: 11743227 (Publication Type: Journal Article)

Chemical References

• Angiotensin Receptor Antagonists
• Enzyme Inhibitors
• Free Radicals
• Lipid Peroxides
• Receptor, Angiotensin, Type 1
• Tetrazoles
• Vasodilator Agents
• Angiotensin II
• Nitroprusside
• omega-N-Methylarginine
• Valsartan
• Tiopronin
• Valine
• Acetylcholine
• Oxygen

Topics

• Acetylcholine (pharmacology)
• Angiotensin II (metabolism)
• Angiotensin Receptor Antagonists
• Animals
• Endothelium, Vascular (physiopathology)
• Enzyme Inhibitors (pharmacology)
• Free Radicals (metabolism)
• Hemodynamics (drug effects)
• In Vitro Techniques
• Lipid Peroxides (metabolism)
• Male
• Myocardial Infarction (metabolism, pathology, physiopathology)
• Myocardium (metabolism, pathology)
• Nitroprusside (pharmacology)
• Oxygen (metabolism)
• Rabbits
• Receptor, Angiotensin, Type 1
• Tetrazoles (pharmacology)
• Tiopronin (pharmacology)
• Valine (analogs & derivatives, pharmacology)
• Valsartan
• Vasodilator Agents (pharmacology)
• Ventricular Remodeling
• omega-N-Methylarginine (pharmacology)