Arginine vasopressin has been implicated in the renal water retention and dilutional hyponatremia associated with congestive heart failure.

A study examined the renal effects of a V2 receptor arginine vasopressin ( AVP ) antagonist in heart failure.

The drug under investigation, called Lixivaptan, appears to be as effective as a diuretic in helping patients get rid of excess water and has the added benefit of retaining proper levels of sodium in the body, said William Abraham, at Ohio State University Medical Center and lead author of study.

The study results are published in the Journal of the American College of Cardiology.

Diuretics become part of life for many patients with congestive heart failure, a disease characterized by fluid retention that can lead to shortness of breath, swollen legs and ankles, and progressive weakening of the heart. Though they are key to reducing fluid, diuretics can cause the kidneys to excrete more sodium than water, which can have damaging effects. An abnormally low concentration of sodium in the blood leads to another chronic condition called hyponatremia, which can slow thinking and cause memory problems, and indicates a poor prognosis for patients with heart failure.

Lixivaptan acts by blocking vasopressin, an anti-diuretic hormone that causes the kidneys to retain water. When the body needs to remain hydrated under certain conditions, vasopressin can have protective effects. But an excess of vasopressin is counterproductive in a body retaining too much fluid, Abraham said.

" Lixivaptan is a vasopressin receptor antagonist, so it signals the kidneys to excrete water, not salt," said Abraham. " It shifts the balance of water and electrolytes to a more favorable state, keeps sodium in and reduces other adverse effects on kidney function. It could be a great adjunct to treatment in heart failure patients with fluid retention."

The study involved 42 patients with class II or class III congestive heart failure, meaning they experienced mild to marked limitation of activity and were generally able to engage in only mild exertion. Of those, 30 patients took varying doses of Lixivaptan and 12 patients received a placebo.

At every dose but the lowest ( 10 milligrams ), Lixivaptan produced a significant increase in urine volume over four hours when compared to placebo, and over 24 hours, the output ranged from 1.8 liters in the placebo group to 3.9 liters in patients receiving 400 milligrams of Lixivaptan. In addition, Lixivaptan dramatically increased solute-free water excretion, meaning the urine from patients taking the drug removed more water than sodium from the body.

The apparent effectiveness of the drug not only holds promise as a new treatment for heart failure patients, but also helps clarify the role vasopressin appears to play in the water retention and low sodium concentration in the first place, Abraham said. He and colleagues suggested that a vasopressin antagonist may also be useful in treating hyponatremia that occurs in heart failure patients who are not taking diuretics but who still experience its effects because of an imbalance of water and salt.

About 90 percent of hospitalizations associated with heart failure are related to water retention. Congestive heart failure affects an estimated 5 million Americans, and is characterized by a reduced ejection fraction – a measurement of how well the heart is squeezing, and often by this seepage of fluid into the lungs, feet, legs or abdominal cavity.

Source: Ohio State University Medical Center, 2006


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