Jeffrey Hord, B.S.
Our bodies attempt to maintain a constant internal environment but achieving this consistency can be made much more difficult when we alter our external environment, such as going from walking upright to being bedridden for five days in the hospital. This change in the external environment alters the load on skeletal muscle fibers and will result in an altered internal environment. Increased levels of oxidative stress in the muscle eventually lead to muscle loss. In a rodent model of muscle inactivity, hindlimb unloading, the onset of oxidative stress production is likely to be marked by the presence of the enzyme complex known as NAD(P)H oxidase (NOX), which becomes functional when multiple subunits come together in an ordered fashion. But what signals the formation of these NOX subunits?
In vascular smooth muscle, angiotensin II can bind to angiotensin II type 1 receptor (AT1R) which can interact with NOX subunits, initiating the formation of the NOX complex and the subsequent rise in oxidative stress. The rise is oxidative stress from the AT1R-NOX interaction can be reduced by blocking the AT1Rs. Blocking AT1R has been a popular and effective method of regulating blood pressure with several FDA-approved medications available, including Losartan. It has been shown that AT1R blockers are beneficial for the treatment of a variety of disorders including hypertension, diabetic neuropathy, and have even been recently touted as a cognitive enhancer in persons with normal blood pressure. Novel studies have proven that AT1R blockers are effective countermeasures against skeletal muscle disorders like Duchenne muscular dystrophy and sarcopenia (muscle loss due to aging), proving once again that AT1R blockers are beneficial for more than just regulation of blood pressure.
Drug development is usually a pain-staking process involving years and years of laboratory testing and clinical trials. Obviously, there are benefits to finding alternative uses of already FDA-approved mediations. Aside from determining the cause of oxidative stress that accompanies muscle inactivity, another goal is to discover a new use for a government approved drug, Losartan. Because of the recently discovered benefits that Losartan offers towards individuals with muscle disorders, our lab believes the administration of AT1R blockers for the purpose of preventing oxidative stress and atrophy during muscle inactivity could be safe, effective, and an affordable method of maintaining muscle size and strength.