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SFVAMC study may revive old approach to high blood pressure therapy

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 fewe
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
1-Jul-2002


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