The discovery of Viagra as a treatment for male erectile dysfunction was accidental. Researchers had been developing the drug for the treatment of hypertension when they discovered an interesting side effect — a change in erectile function. But Rakesh C. Kukreja, Ph.D., VCU professor of internal medicine and cardiology and NIH MERIT recipient, has brought the research back to its initial focus and found a potentially important use for this class of male impotence drugs — heart protection.
Kukreja’s laboratory is one of the first to explore the area of “preconditioning,” 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 heart that is preconditioned or pretreated with Viagra, generically known as sildenafil, has an improved ability to produce nitric oxide and directly improves a patient’s outcome following a heart attack. Generally, damage following a heart attack is related to an inability to recover from lack of oxygen.
In 2006, Kukreja’s group found that another widely used erectile dysfunction drug, Levitra, generically known as vardenafil, showed similar protective effects to sildenafil. He and his team demonstrated for the first time that pretreatment with a clinically relevant dose of vardenafil induces a protective effect against heart attack injury by opening the mitochondrial KATP channel in an animal model. Vardenfil, like sildenafil, stabilizes the mitochondria and protects against damage of the heart by opening the mitochondrial channels in cardiac cells.
Mitochondria are cellular organelles critical for converting oxygen into ATP, the key fuel for cellular function.
Kukreja said that the PDE-5 inhibitors — drugs that help dilate the arteries — might be developed for future use to protect the brain, liver and other organs against ischemic injury: those injuries that are caused by lack of oxygen.
Kukreja’s laboratory has three studies currently funded by the National Institutes of Health, one by the American Heart Association and two from the pharmaceutical industry providing a total of more than $6 million for work in this area.
