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Nitric oxide: Key to cardiovascular and pulmonary function and drug effectiveness

with all manner of stimuli, including circulating factors such as adrenaline, as well such diverse sensory signals as odorants and light. The activation of these receptors leads to the propagation of intracellular signals. Once activated the receptors are quickly turned-off by an enzyme called a G protein-coupled receptor kinase. This process is called desensitization and can limit the effectiveness of many drugs, such as opiates for pain and adrenaline for asthma, and is further associated with numerous diseases including those of the cardiovascular and pulmonary systems. If activated for a long period of time the receptors are carried into the cell and are "turned off."

In animal, cellular and biochemical experiments, the researchers found that a lack of nitric oxide leads to a decrease in beta adrenergic receptor number and function. Also, the researchers found that when SNO compounds were administered to mice they could prevent the receptors from being "turned off" by the drugs.

The researchers said these findings, if confirmed in humans, open up new avenues for the development of non-desensitizing drugs not only for heart failure and asthma but also for other conditions such as pain and high blood pressure.

"We demonstrated that when one of the systems goes awry, so does the other," said Stamler, whose laboratory has made many fundamental discoveries about the role of nitric oxide in human biology, including the discovery of SNOs' ubiquitous role in human health and disease. "When nitric oxide function is impaired by disease, therapeutic agents like beta-agonists in asthma and adrenergic stimulants in heart failure will work less well. The key now is to determine how best to manipulate these ubiquitous receptors, together with nitric oxide for the treatment of human diseases."

"In broad terms, the results of these experiments present a novel role for nitric oxide in regulating the activity of G-protein coupled receptors,
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Source:Duke University Medical Center


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