A study, led by researchers at The Ohio State University Heart Center, has assessed the renal effects of a V2 receptor arginine vasopressin ( AVP ) antagonist in heart failure.

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

Researchers examined the effects of the oral, non-peptide, selective V2 receptor antagonist Lixivaptan in 42 diuretic-requiring patients with mild-to-moderate heart failure in a randomized, double-blind, placebo-controlled, ascending single-dose study.

After overnight fluid deprivation, patients received single-blind placebo on day -1 ( baseline ) and double-blind study medication ( placebo [ n = 12 ] or Lixivaptan 10, 30, 75, 150, 250, or 400 mg [ n = 5 per dose group ]) on day 1, followed by 4 h of continued fluid restriction and additional 20 h with ad libitum fluid intake.

At all but the 10-mg dose, Lixivaptan produced a significant and dose-related increase in urine volume over 4 h, compared with placebo ( p < 0.01 ).
These increases in urine volumes were accompanied by significant increases in solute-free water excretion.

At higher doses, serum sodium was significantly increased; arginine vasopressin antagonism was well tolerated in these patients.

“ These observations confirm a role for arginine vasopressin in the renal water retention associated with heart failure and suggest that the V2 receptor antagonist Lixivaptan may be a promising therapeutic agent for the treatment of heart failure, “ the researchers conclude.

Source: Journal of American College of Cardiology, 2006


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