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Viagra shows potential vasopressin-independent cGMP signaling in certain diabetes

BETHESDA, Md. (June 29, 2005) Normally your kidneys filter about 50 gallons of blood a day, remove such waste as salts and minerals, and concentrate it into urine. When you exercise or don't take in water, your blood "thickens" and instead of removing water, the kidney reverses the process, pulls in water from the body that would normally go into the urine, and puts it into the blood, thus maintaining water balance.

Various diseases disrupt this process and in one small population the kidneys keep dumping watered-down urine into the bladder, at the rate of about 5 gallons a day compared with the normal quart or so. Besides the obvious inconvenience, people with nephrogenic diabetes insipidus (NDI) are constantly thirsty and in danger of severe dehydration, electrolyte imbalance, and have other problems that may ultimately require a kidney transplant.

Wanted: way to bypass defective vasopressin receptors

While the disease is rare, its cause is known, involving malfunctioning receptors (V2R) for the anti-diuretic hormone vasopressin. Based on their earlier work, researchers at Massachusetts General Hospital-Harvard Medical School, Boston, believed they might be able to bypass the V2R and alleviate NDI symptoms by activating the kidney's water channels, called aquaporins, through a different mechanism.

Their study, entitled "Stimulation of AQP2 membrane insertion in renal epithelial cells in vitro and in vivo by the cGMP phosphodiesterase inhibitor sildenafil citrate (Viagra)," is in the June issue of the American Journal of Physiology-Renal Physiology, published by the American Physiological Society. The research was conducted by Richard Bouley, Nuria Pastor-Soler, Ori Cohen, Margaret McLaughlin, Sylvie Breton and Dennis Brown at Massachusetts General Hospital (MGH) and Harvard Medical School, Boston.

Dennis Brown, director of the Program in Membrane Biology in the MGH Renal Unit, said "it's a target-trafficking proble
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29-Jun-2005


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