Effects of antioxidants on coronary microvascular spasm induced by epicardial coronary artery endothelial injury in pigs.

Abstract

OBJECTIVES:

The effect of oxidative stress on coronary microvascular disease is unknown. We investigated whether chronic administration of ascorbic acid (ASC) or glutathione (GSH) prevents microvascular dysfunction and remodeling induced by upstream repeated coronary artery endothelial injury.

METHODS:

Balloon endothelial injury was repeated at the left anterior descending coronary artery (LAD), just distal to an implanted flow meter, every 2 weeks for 6 weeks in pigs. Changes in LAD blood flow induced by acetylcholine (ACh) and 5-hydroxytryptamine were assessed before each endothelial injury and at 8 weeks after the first endothelial injury in pigs without treatment (endothelial injury group, n = 12) and in pigs treated with oral ASC (3 g/day) (ASC group, n = 12) and ASC (3 g/day) plus GSH (1 g/day) (ASC + GSH group, n = 12).

RESULTS:

In the endothelial injury group, reduced blood flow in response to ACh was augmented from a decrease of 18 +/- 17% to a decrease of 100% (that is, zero flow, 8 weeks, P < 0.01), accompanied by an increase of ascorbyl free radicals (AFRs) in coronary sinus blood. In contrast, in the ASC + GSH group, blood flow response to ACh was altered to a decrease of 45 +/- 17% (8 weeks, P < 0.01 compared with the endothelial injury group), coronary sinus blood AFRs did not change (8 weeks, 21.4 +/- 12.5 signal intensities, P < 0.01 compared with the endothelial injury group) and the rate of platelet aggregation induced by adenosine diphosphate was small (8 weeks, 56 +/- 17%, P < 0.01 compared with the endothelial injury group).

CONCLUSIONS:

Chronic administration of antioxidants suppressed microvascular hypercontraction, suggesting that it may be a promising therapeutic strategy for treating coronary microvessel disorders, including microvascular angina.

• Authors: Kazuhiko Aikawa, Shu-Ichi Saitoh, Mitsuru Muto, Taku Osugi, Ken Matsumoto, Futoshi Onogi, Kazuhira Maehara, Hiroyuki Yaoita, Yukio Maruyama
• Journal: Coronary artery disease (Coron Artery Dis) Vol. 15 Issue 1 Pg. 21-30 (Feb 2004) ISSN: 0954-6928 [Print] England
• PMID: 15201617 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 Lippincott Williams & Wilkins

Chemical References

• Antioxidants
• Biomarkers
• Free Radical Scavengers
• Free Radicals
• Thromboxane B2
• 6-Ketoprostaglandin F1 alpha
• Adenosine Diphosphate
• Glutathione
• Ascorbic Acid

Topics

• 6-Ketoprostaglandin F1 alpha (blood)
• Adenosine Diphosphate (blood)
• Animals
• Antioxidants (administration & dosage, metabolism)
• Ascorbic Acid (administration & dosage, blood)
• Biomarkers (blood)
• Blood Pressure (drug effects)
• Coronary Circulation (drug effects)
• Coronary Vasospasm (drug therapy, etiology, metabolism)
• Disease Models, Animal
• Endothelial Cells (drug effects, metabolism)
• Endothelium, Vascular (drug effects, injuries, metabolism)
• Free Radical Scavengers (administration & dosage, blood)
• Free Radicals (blood)
• Glutathione (administration & dosage, blood)
• Heart Rate (drug effects)
• Models, Cardiovascular
• Oxidative Stress (drug effects)
• Pericardium (drug effects, injuries, metabolism)
• Platelet Aggregation (drug effects)
• Swine
• Thromboxane B2 (blood)
• Time Factors