Caveats, next steps and implications for other diseases

However, Brown warned that aquaporin accumulation is "only one step in the cascade, and we have shown that a clinically approved drug has a useful effect. However, now we need to understand the physiology of the whole kidney." Other "next steps" include:

• Since the enzyme inhibited by Viagra is in vascular cells as well as in kidney cells, administration of Viagra also increases blood flow, putting extra pressure on kidneys.

• Recent evidence indicates that PDE5 inhibition is associated with excretion of abnormal amounts of sodium in the urine.

• Because the present study was performed over a short time period, only a small effect on final urine concentration was found. Long-term studies need to now be carried out, and combination therapy as well as maintenance of subjects on a low-sodium diet need to be tested.

• The paper adds: "metabolism of sildenafil citrate between human and rat is different."

Although statistics are hard to come by, fewer than 700 Americans, mostly male, have inherited forms of NDI. Many more patients have acquired NDI through using certain prescription drugs, or other physical conditions or diseases, but the total is still small.

"Studying the vasopressin receptor's mutations that affect urine concentration was a chance to understand the role of some amino acids or sequence motifs on this protein in cell physiology," lead author Bouley said. "This knowledge may be applied to other proteins and other diseases involving protein trafficking, including cystic fibrosis, where abnormal proteins trapped in cells can't perform their normal physiological function," Bouley noted.

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29-Jun-2005