Viagra eases exercise-induced fatigue in mice models

October 27th, 2008 - 2:43 pm ICT by IANS  

Washington, Oct 27 (IANS) Viagra has been found to ease exercise-induced fatigue in dystrophic mice models by overcoming a faulty signalling pathway that causes it, according to research. A University of Iowa study suggests that prolonged fatigue after mild exercise experienced by people with muscular dystrophy is distinct from the inherent muscle weakness caused by the disease.

Muscular dystrophy (MD) refers to a group of genetic, hereditary muscle diseases that cause progressive muscle weakness. Researchers showed that Viagra could alleviate fatigue in such mice.

“Our research suggests that there probably are many different neuromuscular conditions where fatigue could be treated by targeting this newly discovered pathway,” said Kevin Campbell, University of Iowa professor and head of molecular physiology and biophysics.

Using animal models, the researchers showed that if an enzyme called neuronal nitric oxide synthase (nNOS) is not present at its normal location on the muscle membrane, then blood vessels that supply active muscles do not relax normally and the animals experience post-exercise fatigue.

Early clues about the role of nNOS came from observing that the significant inactivity of dystrophic mice following mild exercise was very similar to the fatigue experience by muscular dystrophy patients after a short period of walking.

Working with mouse models of muscular dystrophy and normal mice engineered to lack nNOS, the university team, including study co-author Yvonne Kobayashi, research associate in molecular physiology and biophysics, showed that mice with misplaced or missing nNOS exhibited prolonged fatigue after mild exercise.

“The mice without nNOS have normal muscles and can exercise quite well, but after just mild exercise, we found that they had the intense fatigue response,” Kobayashi said, according to a university press release.

“The signalling pathway probably maintains blood flow into the muscle during exercise and keeps the blood flow going after exercise. But when nNOS is missing or mislocalised, this pathway breaks down,” Campbell explained.

To determine if nNOS was affected in humans with muscular dystrophy, Steven Moore, professor of pathology and study co-author, examined muscle biopsies from 425 patients with many different forms of muscular dystrophy. He found that nNOS was missing or reduced in most cases, suggesting a common mechanism of fatigue.

The enzyme nNOS makes a signalling molecule called nitric oxide, which stimulates production of a chemical called cGMP that causes smooth muscle around blood vessels to relax thereby increasing blood flow.

This nitric oxide signalling pathway is turned off by phosphodiesterase (PDE), an enzyme that breaks down cGMP, according to findings published in Nature Advance Online Publication Sunday. Viagra, a drug designed to increase blood flow, inhibits PDE and prolongs the existence of the cGMP molecules that promote blood vessel dilation.

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