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Title: Long-term effects of nonpeptide vasopressin V2 antagonist OPC-31260 in heart failure in the rat.
Austin Authors: Burrell, Louise M ;Phillips, P A;Risvanis, John;Chan, Robert K ;Aldred, K L;Johnston, Colin I
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg 3084, Victoria, Australia
Issue Date: 1-Jul-1998
Publication information: The American Journal of Physiology; 275(1 Pt 2): H176-82
Abstract: The hormone arginine vasopressin (AVP) contributes to water retention and vasoconstriction in congestive heart failure (CHF) through effects at the V2 and V1a receptors, respectively. The effect of long-term V2 receptor (V2R) 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-1 . day-1) 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 V2R blockade increased 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). V2R 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 using OPC-31260 may represent an alternative to standard diuretic therapy in the management of water retention that characterizes heart failure.
Gov't Doc #: 9688911
Journal: American Journal of Physiology
Type: Journal Article
Subjects: Animals
Antidiuretic Hormone Receptor Antagonists
Arginine Vasopressin.blood
Blood Pressure.drug effects
Body Weight.drug effects
Diuresis.drug effects
Heart.drug effects.physiopathology
Heart Failure.etiology.physiopathology
Hemodynamics.drug effects.physiology
Lung.drug effects.physiopathology
Myocardial Infarction.complications.physiopathology
Organ Size.drug effects
Rats, Sprague-Dawley
Renin-Angiotensin System
Survival Analysis
Appears in Collections:Journal articles

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