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Home > Press Center > Press Releases from 2005 Annual Meeting > Blocking angiotensin receptor may suppress abdominal aortic aneurysms

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Jill Goodwin
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The formation of abdominal aortic aneurysms is a complex vascular process dependent on numerous factors. One potential critical factor appears to depend on a particular receptor on vascular cells, according to research presented today at the annual meeting of the Society for Vascular Surgery in Chicago. Blocking these angiotensin-II receptors with drugs known as angiotensin-receptor antagonists, such as losartan, may play a critical role in suppressing the development of abdominal aortic aneurysms (AAA).

Angiotensin-II is a substance that exerts many effects on the vascular system and is known to play a critical role in the formation of AAAs. It acts on both the AT1 and the AT2 receptors on the vascular cells. The purpose of this study was to determine whether removing these receptors would influence the development of AAAs, using an experimental mouse model. Researchers induced AAAs in three groups of mice: 10 normal mice that served as controls, 10 mice genetically engineered to have deleted AT1 receptors, and 10 mice genetically engineered to have deleted AT2 receptors. Two weeks later, large aortic aneurysms had developed, enlarging the diameter of the vessel by approximately 150%, in the control mice and the mice with the missing AT2 receptors. But the aortic diameter had only increased by 76% in the mice with the missing AT1 receptors. “The lack of AT1 receptors in this mouse model appeared to protect against the development of AAAs, while the lack of AT2 receptors didn’t appear to affect aneurysm formation,” said Dr. Jack Oak of the Washington University School of Medicine, St. Louis.

Systolic and diastolic blood pressures also were significantly lower in the mice with deleted AT1 receptors, but not in the other two groups of mice. To determine whether the suppression of AAAs was due to decreased blood pressure, the researchers administered a drug that lowers blood pressure, hydralazine, to a fourth group of mice with induced AAAs. The hydralazine lowered their blood pressure but did not suppress aneurysm formation. These results indicate that the AT1 receptor’s effects on AAAs are independent of its effects on blood pressure. More important, using a drug to block the AT1 receptor suppressed the formation of AAAs, just as deleting the receptors through genetic engineering did. If these results can be replicated in human studies, “AT1 receptor antagonists may have a role in the medical management of patients who have small, asymptomatic AAAs,” Dr. Oak noted.

The aorta is the largest artery in the body and carries blood away from the heart. The abdominal aorta is the portion of that artery that runs through the abdomen and supplies blood to the lower body. When a weak area of the artery expands or bulges, it is called an abdominal aortic aneurysm. A normal aorta is about 1 inch in diameter, but an aneurysm can stretch the artery much wider and can even make it burst, causing severe internal bleeding that can be fatal. If it is diagnosed early, AAA can be treated and even cured. Approximately 200,000 cases of AAA are diagnosed every year in the United States, and nearly 15,000 of these are considered at risk of rupturing.