SFVAMC study may revive old approach to high blood pressure therapy

July 01, 2002

A class of once-popular high blood pressure drugs, now used less frequently because of serious side effects, may be re-explored in light of San Francisco Veterans Affairs Medical Center research. The new study in mice suggests that drugs which block just one type of adrenalin receptor might be just as effective as the earlier, related drugs, but with fewer side effects. The earlier drugs block more types of adrenalin receptors.

"In clinical trials a few years ago, drugs that blocked all three types of alpha-1 adrenergic receptors increased patients' risk of heart disease, so their use has fallen. Our study suggests that a drug which blocks just one receptor subtype might reduce blood pressure just as effectively, while avoiding some of the side effects," said Paul Simpson, MD, UCSF professor of medicine and cardiologist at SFVAMC.

For their study, the researchers created genetically engineered mice that lacked the A/C subtype of alpha-1-adrenergic receptor. Adrenergic receptors throughout the body create the response to the stress hormones adrenalin and noradrenalin.

The experimental mice had 8 to 12 percent lower blood pressure than normal mice. This suggested that A/C receptors can increase blood pressure, and that blocking them alone might reduce blood pressure, Simpson said.

Interestingly, the previously tested drugs that blocked alpha-1 receptors, reduced blood pressure in people by the same amount as did the gene knockout in mice, Simpson said.

The study was published in the latest issue of Proceedings of the National Academy of Sciences.

In addition to measuring resting blood pressure using two different techniques, they also treated the mice with a drug that raises blood pressure. While the drug raised blood pressure in both normal and genetically altered mice, the experimental mice still had 10-15 percent lower blood pressure, Simpson said.

Drugs that block the A/C receptor subtype might have fewer side effects because of the receptor's distinct pattern of expression in blood vessels, said Gregg Rokosh, PhD, the study's co-author and now an assistant professor of medicine at University of Louisville. "We found this subtype is predominantly expressed in peripheral arteries and not in arteries supplying the heart and brain. Therefore blocking the A/C receptor should only affect the areas that are important for regulating blood pressure," Rokosh said.

Simpson plans to study how alpha-1 A/C and other alpha adrenergic receptor types affect the heart's growth and development.

According to the American Heart Association, high blood pressure, defined as a systolic reading greater than 140 or diastolic greater than 90, increases risk of heart attack and stroke.

High blood pressure can be treated in many ways including losing weight, exercising, reducing dietary salt and sodium, and moderating alcohol consumption. There are numerous drugs commonly used to treat high blood pressure, which have a range of benefits and side effects. The most common drugs include beta-blockers (which block beta adrenergic receptors), diuretics, ACE inhibitors, and blood vessel dilators.
The study was supported by funds from the American Heart Association, Canadian Heart and Stroke Association, Department of Veterans Affairs, and the National Institutes of Health.

The San Francisco Veterans Affairs Medical Center has been a primary affiliate of University of California San Francisco since 1974. The UCSF School of Medicine and the SFVAMC collaborate to provide education and training programs for medical students and residents at SFVAMC. SFVAMC maintains full responsibility for patient care and facility management of the medical center. Physicians at SFVAMC are employed by the Department of Veterans Affairs and also hold UCSF faculty appointments.

University of California - San Francisco

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