LONG-TERM EFFECTS OF NONPEPTIDE VASOPRESSIN V-2 ANTAGONIST OPC-31260 IN HEART-FAILURE IN THE RAT

The hormone arginine vasopressin (AVP) contributes to water retention and vasoconstriction in congestive heart failure (CHF) through effects at the V-2 and V-1a receptors, respectively. The effect of long-term V-2 receptor (V2R) blockade using OPC-31260 was assessed in a rat mode l of postinfarction-induced CHF. Rats underwent coronary artery ligati on or sham operation and were treated for 6 mo with oral OPC-31260 (10 mg.kg(-1).day(-1)) or vehicle. CHF was characterized by left ventricu lar remodeling and impaired systolic function, increased cardiac and l ung weight, and elevated plasma atrial natriuretic peptide; plasma AVP and plasma renin activity were not increased. Chronic V2R blockade in creased urine volume (P < 0.01) and decreased urine osmolality (P < 0. 01) but had no natriuretic effects. V2R blockade did not activate the renin-angiotensin system but increased plasma AVP in CHF (P < 0.01). V 2R blockade did not influence cardiac remodeling, cardiac function, or survival. These results suggest that AVP plays a major role in water retention through the renal V2R in a rat model of CHF. V2R blockade us ing OPC-31260 may represent an alternative to standard diuretic therap y in the management of water retention that characterizes heart failur e.