10 September 2014
Researchers at the Temple University School of Medicine, Pennsylvania, have discovered a new target that could aid the treatment of heart failure.
When a heart enters failure, its ability to pump blood through the circulatory system is weakened, which triggers the release of a neurohormone that interferes with the heart's best chance to improve contractility. This is according to the new study carried out by the Temple University researchers.
The findings, published in the American Heart Association journal, Circulation, could potentially lead to new treatment options for patients in the latter stages of heart failure. The discovery also sparks more questions about why a drug used to treat some patients in end-stage heart failure is able to improve symptoms but cannot extend lives or reduce hospital admissions.
Professor Douglas Tilley, a pharmacology assistant professor at Temple University, said this is a new mechanism that regulates cardiac function and has never really been appreciated before.
He, along with Professor Arthur Feldman, executive dean and professor of medicine at Temple's School of Medicine, led the work examining the effect of arginine vasopressin (AVP), which heart failure patients overproduce. Although it has long been determined that higher AVP levels make death more likely, no one has been able to find out why there is this connection.
It had been assumed that vasopressin had two principal roles: increasing blood pressure by narrowing arteries due to its reaction with the vasopressin type 1A receptor, and encouraging the kidneys to absorb more water and produce less urine with the vasopressin type 2 receptor. However, the direct impact of vasopressin on the heart itself is unknown, but many believe it does not play a key role.
During their tests, the researchers dismissed any observed changes in heart function as a byproduct of vasopressin's action as a vasoconstrictor, which was making the heart work harder, according to the team.
Using two ex vivo hearts, the researchers determined that the effect of vasopressin type 1A receptor on cardiac function was independent of its role as a vasoconstrictor and it was actually preventing the heart from getting important information.
They found that vasopressin interferes with the body's own attempt to rescue a failing heart, according to the researchers. When the heart muscle starts to lose its ability to contract, the body releases catecholamines and make the heart work harder. This new research found that vasopressin impairs the catecholamine receptors so that the heart never gets signals telling it to support the flaccid muscles.
"This makes the heart vasopressin receptor, or some of the downstream signaling, a new and important target for therapies in patients with heart failure," Professor Feldman said. "If the V1 receptor could be blocked, or its signal interrupted, catecholamine signals could get through."
This finding could be important for patients in the latter stages of heart failure when their kidneys hold on to too much water, as they can be given drugs to stop the water retention but this often boost levels of vasopressin.
Posted by Jeanette Royston
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