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VCU Research Shows Erectile Dysfunction Drug Reduces Death Of Heart Cells In Heart Attack Model

Date:
February 3, 2005
Source:
Virginia Commonwealth University
Summary:
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.

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.

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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 Kukreja, sildenafil not only protected against necrosis, accidental cell death occurring due to oxygen deprivation, but also against apoptosis, cell death following DNA fragmentation. Furthermore, the researchers found the presence of phosphodiesterase-5 (PDE-5), an enzyme responsible for the destruction of the cGMP molecule, in the heart cells. The cGMP is an intracellular messenger molecule that plays an important role in the dilation of arteries in the body. Sildenafil is able to preserve cGMP, and therefore dilation of the arteries by inhibiting PDE-5.

“These observations have far-reaching implications for the treatment of patients with heart failure where loss of cells is primarily due to apoptosis,” he said.

Kukreja and his colleagues began studying sildenafil in 2002 as part of an on-going research program into “preconditioning,” which is a way to protect the heart muscle from serious damage in the future by depriving it for very brief periods of blood flow and, therefore, oxygen. In papers published in the September 2002 issue of the American Journal of Physiology, and the March 2003 issue of Circulation Research, Kukreja and his colleagues observed a powerful, protective effect of sildenafil in the heart during experimental heart attack in animal models.

This research is supported by a grant from the National Institutes of Health.


Story Source:

The above story is based on materials provided by Virginia Commonwealth University. Note: Materials may be edited for content and length.


Cite This Page:

Virginia Commonwealth University. "VCU Research Shows Erectile Dysfunction Drug Reduces Death Of Heart Cells In Heart Attack Model." ScienceDaily. ScienceDaily, 3 February 2005. <www.sciencedaily.com/releases/2005/02/050201102257.htm>.
Virginia Commonwealth University. (2005, February 3). VCU Research Shows Erectile Dysfunction Drug Reduces Death Of Heart Cells In Heart Attack Model. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2005/02/050201102257.htm
Virginia Commonwealth University. "VCU Research Shows Erectile Dysfunction Drug Reduces Death Of Heart Cells In Heart Attack Model." ScienceDaily. www.sciencedaily.com/releases/2005/02/050201102257.htm (accessed October 25, 2014).

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