A new study says that viagra can overcome the signalling defect and relieve exercise-induced fatigue associated with muscular dystrophies.
In the study on mice, researchers at University of Iowa showed that Viagra could alleviate fatigue in the animals with mislocalized enzyme called neuronal nitric oxide synthase (nNOS).
They also showed that there was a difference between the prolonged fatigue after mild exercise in muscular dystrophy patients and the inherent muscle weakness caused by the disease.
The researchers identified a faulty signalling pathway that apparently leads to exercise-induced fatigue in mouse models of muscular dystrophy.
Also, the study, led by Yvonne Kobayashi, Ph.D., UI research associate in molecular physiology and biophysics, showed that targeting the signalling pathway might help develop therapies to treat this type of fatigue.
"This is an exciting finding and our research suggests that there probably are many different neuromuscular conditions where fatigue could be treated by targeting this newly discovered pathway," Nature magazine quoted Kevin Campbell, Ph.D., UI professor and head of molecular physiology and biophysics, as saying.
The researchers used animal models, to show that if nNOS is absent from 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.
The role of nNOS was evident form the fact 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.
Campbell said: "A clinician colleague said, 'Those mice behave just like my patients with Becker muscular dystrophy.' As soon as he said that we knew what might be going on, because Becker patients have mislocalized nNOS."
While working with mouse models of muscular dystrophy and normal mice engineered to lack nNOS, the researchers showed that mice with misplaced or missing nNOS exhibited prolonged fatigue after mild exercise.
The enzyme nNOS makes a signalling molecule called nitric oxide, which triggers the production of a chemical called cGMP leading to the relaxation of smooth muscle around blood vessels, which in turn increases the blood flow.
This nitric oxide signalling pathway is turned off by phosphodiesterase (PDE), an enzyme that breaks down cGMP.
Viagra is designed to increase blood flow and it inhibits PDE and prolongs the existence of the cGMP molecules that promote blood vessel dilation. The researchers then showed that Viagra could ease fatigue in mice with mislocalized nNOS.
"The mice that have the nNOS mislocalized still have some nitric oxide signaling, but the Viagra enhances that signal by inhibiting PDE and preventing breakdown of cGMP," said Campbell.
The study is published in Nature Advance Online Publication.