Hypertension Drug Effective at Preventing Atherosclerosis

April 4, 2000

Blocking the hormone that causes high blood pressure can reduce the development of heart vessel disease, report researchers from Wake Forest University Baptist Medical Center in this week''s issue of Circulation.

The research team found that the hypertension drug Losartan reduced by half the buildup of fatty deposits in the heart vessels of monkeys fed a high-fat diet. The drug works by blocking angiotensin II, a hormone that causes high blood pressure and in recent years has been suspected as a cause of blood vessel disease.

"Evidence is mounting that there is a basic hormonal mechanism that causes the various facets of cardiovascular disease," said Carlos Ferrario, M.D., director of the Hypertension and Vascular Disease Center.

"The results imply that in order to prevent plaque buildup in vessels, we may need to treat not only cholesterol, but to treat the hormone linked to hypertension," said Ferrario. "Cholesterol-lowering drugs prevent heart attacks in only about 30 percent of people who take them. Perhaps we could improve those statistics by also treating angiotensin II."

The study used cynomolgus monkeys that didn''t have high blood pressure. The monkeys, which have marked similarities to humans in the development of cardiovascular disease, were fed a high-fat diet that raised their cholesterol levels to about 300. From previous studies, the researchers knew that fatty streaks, the first sign of vessel disease, begin to form after 18 weeks on the diet. At 12 weeks, half of the monkeys received Losartan for six weeks. After 20 weeks on the diet, the researchers found that fatty streak development was reduced by 50 percent in the monkeys that received Losartan. There were no changes in cholesterol or blood pressure levels that could have accounted for the difference.

"What we have is further evidence that angiotensin II is involved in the initiation of atherosclerosis," said William Strawn, D.V.M, Ph.D., the article''s lead author. "It appears that the hormone is actually a risk factor for developing blood vessel disease."

Researchers believe Losartan''s effect was caused by the drug''s ability to protect low-density lipoproteins, the so-called "bad" cholesterol, from oxidization. Oxidation increases the toxic effect of cholesterol on arteries.

"These drugs are obviously more than hypertensive agents," said Ferrario. "The results suggest that treating hypertensive patients with drugs to block the actions of angiotensin II will slow down or prevent the development of atherosclerosis."

Ferrario said it is too early to recommend that non-hypertensive patients be treated with Losartan. He predicted, however, that future treatments for patients with high cholesterol and other risk factors for heart attack might include both lipid-lowering and anti-hypertensive drugs. He called for additional research to duplicate the findings in humans and to understand the mechanisms that cause hypertension and atherosclerosis.

Other members of the research team were Mark C. Chappell, Ph.D., and Richard H. Dean, M.D., from the Medical Center and Salah Kivlighn, Ph.D., from Merck & Co., which manufactures Losartan and funded the research.


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