Long-term effects of nonpeptide vasopressin V 2 antagonist OPC-31260 in heart failure in the rat

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 275; no. 1; pp. H176 - H182
• Main Authors: Burrell, Louise M, Phillips, Paddy A, Risvanis, John, Chan, Robert K, Aldred, Kathryn L, Johnston, Colin I
• Format: Journal Article
• Language: English
• Published: United States 01.07.1998
• Subjects: receptors; echocardiography; myocardial infarction; survival
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.1.H176

The hormone arginine vasopressin (AVP) contributes to water retention and vasoconstriction in congestive heart failure (CHF) through effects at the V and V receptors, respectively. The effect of long-term V receptor (V R) blockade using OPC-31260 was assessed in a rat model of postinfarction-induced CHF. Rats underwent coronary artery ligation or sham operation and were treated for 6 mo with oral OPC-31260 (10 mg ⋅ kg ⋅ day ) or vehicle. CHF was characterized by left ventricular remodeling and impaired systolic function, increased cardiac and lung weight, and elevated plasma atrial natriuretic peptide; plasma AVP and plasma renin activity were not increased. Chronic V R blockade increased urine volume ( P < 0.01) and decreased urine osmolality ( P < 0.01) but had no natriuretic effects. V R blockade did not activate the renin-angiotensin system but increased plasma AVP in CHF ( P < 0.01). V R 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 V R in a rat model of CHF. V R blockade using OPC-31260 may represent an alternative to standard diuretic therapy in the management of water retention that characterizes heart failure.