Nitric Oxide release triggered by Viagra is key to heart protection, VCU research shows

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RICHMOND, Va. – In a major breakthrough in understanding how Viagra protects the heart, researchers at Virginia Commonwealth University have found that the popular impotence drug stimulates the release of nitric oxide in heart cells, offering protection to a healthy heart against future damage.

The study shows, for the first time, that Viagra, a drug used to treat erectile dysfunction in men, produces therapeutic levels of the chemical, nitric oxide, which dramatically reduces damage in heart muscle during heart attacks. The study was posted online today (March 13) by Circulation Research, a journal of the American Heart Association. It will appear in the April 4 print edition.

“Nitric oxide is a ubiquitous molecule that is involved in regulating virtually every biological process,” says Rakesh C. Kukreja, Ph.D., professor of internal medicine and Eric Lipman Chair in cardiology at VCU and lead author of the study. “Over the past several years, we’ve seen in animal experiments that nitric oxide plays a fundamental role in the drug-elicited protection of the heart against ischemic attacks. Now we’ve been able to determine that Viagra stimulates the enzymes responsible for production of nitric oxide in the heart.”

In the environment, nitric oxide is a potentially toxic gas that is formed in lightning strikes and car exhaust, creating air pollution and irritating lungs. But, inside the body, nitric oxide plays a very different role. Scientists discovered in the1980s that the body produces nitric oxide molecules, and those molecules help blood vessels to relax. The discovery led to a Nobel Prize in Physiology or Medicine in 1998 to three U.S. pharmacologists and has prompted development of various nitric oxide-driven therapies for the circulatory, immune and nervous systems. One of the most successful and profitable compounds in this class has been sildenafil, which Pfizer Inc. sells under the trade name Viagra. Viagra dilates the blood vessels in penile muscles and induces erections. 

Kukreja and his colleagues at VCU began studying Viagra in early 2002 as part of on-going research into “preconditioning,” which is a way to protect the heart muscle from serious damage in the future by subjecting it to very brief periods of deprivation of blood flow and, therefore, oxygen.  A study published in the September 2002 issue of the American Journal of Physiology – Heart and Circulatory Physiology demonstrated that Viagra induces powerful cardio protective effects in rabbits.

The latest research, funded by grants from the National Institutes of Health and the American Heart Association, advances that work, in tests on mice. Kukreja gave injections of Viagra pills, dissolved in saline, to adult male mice. Viagra dramatically reduced the severity of heart damage in mice during experimental heart attacks. 

Most interestingly, the research showed a significant increase of nitric oxide synthase enzymes in the mouse hearts after injection with Viagra.  This is a major breakthrough in understanding the molecular mechanisms of Viagra-induced heart protection. 

“Viagra therapy for cardio protection could become as important as, or perhaps even more important than, its current use for treatment of erectile dysfunction in men,” Kukreja says.