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VCU research shows erectile dysfunction drug reduces death of heart cells in heart attack model

RICHMOND, Va. (Jan. 31, 2005) Virginia Commonwealth University researchers have shown that a widely used drug for treating erectile dysfunction, Viagra, reduces the death of heart cells under heart attack-like conditions in a laboratory model.

The results are a key finding that may help researchers develop a new treatment for patients with heart failure where the loss of cells is primarily due to cell suicide.

In the Journal of Biological Chemistry, published online Jan. 24, VCU researchers found that treatment with Viagra, generically known as sildenafil citrate, at clinically relevant concentrations produced therapeutic levels of nitric oxide (NO) in the heart cells of mice by increasing protein levels of two enzymes responsible for the synthesis of NO.

Employing a cellular model where heart attack-like conditions are simulated in a Petri dish, they demonstrated that NO produced from sildenafil inhibits cell death by stabilizing mitochondria, increasing the level of the anti-death protein, Bcl-2, and inhibiting caspase 3, the protein considered to be the ultimate weapon in cell suicide.

"This research has established a strong basis for the design of future studies targeted toward investigating the clinical effects of sildenafil on survival of heart muscle following a major heart attack," said Rakesh C. Kukreja, Ph.D., professor of medicine, physiology and biochemistry at VCU, and lead author of the study.

"In addition, these findings suggest that this drug may slow or possibly reverse the progressive loss of heart cells during chronic heart failure in patients with coronary artery disease," he said.

Researchers used heart cells prepared from genetically engineered mice that lack nitric oxide synthesizing enzymes. The model was particularly useful in studying the protective effect of sildenafil in heart muscle cells independent of any vascular effects or other types of cells, Kukreja said.

According to Kukr
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Contact: Sathya Achia-Abraham
sbachia@vcu.edu
804-828-1231
Virginia Commonwealth University
31-Jan-2005


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