scholarly journals Cardiac output improvement by pecavaptan: a novel dual‐acting vasopressin V1a/V2 receptor antagonist in experimental heart failure

2020 ◽  
Author(s):  
Thomas Mondritzki ◽  
Thuy Anh Mai ◽  
Julia Vogel ◽  
Elisabeth Pook ◽  
Pierre Wasnaire ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Receptor Antagonist ◽  
Experimental Heart Failure ◽  
V2 Receptor ◽  
V2 Receptor Antagonist

Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs

1993 ◽  
Vol 265 (4) ◽  
pp. R934-R942 ◽  
Author(s):  
M. Naitoh ◽  
H. Suzuki ◽  
M. Murakami ◽  
A. Matsumoto ◽  
A. Ichihara ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Receptor Antagonist ◽  
Arginine Vasopressin ◽  
Statistical Significance ◽  
Conscious Dogs ◽  
Receptor Blockade ◽  
Vasodilatory Response ◽  
V2 Receptor ◽  
Plasma Arginine ◽  
V2 Receptor Antagonist

In conscious dogs, 36-h water deprivation induced a significant increase in renal blood flow (RBF) with elevation of the plasma arginine vasopressin (AVP) concentration to 9.6 +/- 1.8 pg/ml. To simulate such a condition, a mild elevation of plasma AVP was produced by infusing AVP intravenously at a dose of 0.1 ng.kg-1.min-1 for 20 min. The plasma AVP concentration then increased to 6.8 +/- 0.7 pg/ml. This dose of AVP increased the RBF by 21.7 +/- 2.6% and decreased the renal vascular resistance by 18.1 +/- 2.3% without significant changes in mean arterial pressure, cardiac output, or heart rate. The mechanism of this renal vasodilatory action was examined using newly developed, orally effective, selective AVP antagonists OPC-21268 (a V1-receptor antagonist) and OPC-31260 (a V2-receptor antagonist). In 36-h water-deprived dogs, V2-receptor blockade with OPC-31260 significantly decreased the RBF by 20.5 +/- 2.6% without significant changes in cardiac output. The exogenous AVP-induced renal vasodilatory response tended to be augmented when V1 receptors were blocked by pretreatment with OPC-21268, but the change did not achieve statistical significance. On the other hand, V2-receptor blockade by either pretreatment with OPC-31260 or simultaneous infusion of OPC-31260 inhibited this vasodilatory response. Furthermore, intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) at a dose of 0.3 ng.kg-1 x min-1 for 20 min significantly increased the RBF by 36.5 +/- 1.7%, and this DDAVP-induced renal vasodilation was inhibited by simultaneous infusion of V2-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oral AVP receptor antagonists OPC-21268 and OPC-31260 on congestive heart failure in conscious dogs

1994 ◽  
Vol 267 (6) ◽  
pp. H2245-H2254 ◽  
Author(s):  
M. Naitoh ◽  
H. Suzuki ◽  
M. Murakami ◽  
A. Matsumoto ◽  
K. Arakawa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Output ◽  
Plasma Concentration ◽  
Oral Administration ◽  
Receptor Antagonist ◽  
Conscious Dogs ◽  
Hemodynamic Responses ◽  
Combined Administration ◽  
V2 Receptor

Rapid right ventricular pacing could induce congestive heart failure in conscious dogs with significant increase in plasma concentration of arginine vasopressin (AVP) (from 1.2 +/- 0.2 to 3.4 +/- 0.6 pg/ml). In this experimental model of heart failure, oral administration of the selective AVP V1 receptor antagonist OPC-21268 significantly increased cardiac output and improved renal function without significant changes in serum electrolytes and hormones. Oral administration of the selective AVP V2 receptor antagonist OPC-31260 induced marked water diuresis, which resulted in significant increases in serum sodium concentration, plasma renin activity, and plasma concentration of AVP, although it did not produce hemodynamic improvement. Combined administration of OPC-21268 and OPC-31260 showed supra-additive hemodynamic responses as well as additive renal and metabolic responses, i.e., it showed prolonged decrease in mean arterial pressure and profound increase in cardiac output. These results suggest that AVP plays a significant role in elevation of vascular tone through V1 receptors and plays a major role in retaining free water through V2 receptors in this model of heart failure. Furthermore, combined administration of V1 and V2 receptor antagonists could induce not only metabolic and hormonal responses but also more beneficial hemodynamic responses than those observed following treatment with V1 receptor antagonist alone.

Sign in / Sign up

Export Citation Format

Share Document