Intracerebroventricular Treatment with Vasopressin V₁-Receptor Antagonist Inhibits Centrally-Mediated Pressor Response to Clonidine in Conscious Rats

Abstract

The effect of intracerebroventricular (i.c.v.) treatment with a vasopressin (AVP) V₁-receptor antagonist on the pressor response to i.c.v. injection of clonidine was investigated in conscious rats with chronic i.c.v. guide cannulas and an arterial catheter. In conscious rats, i.c.v.-injected clonidine (5 and 10 μg) dose-dependently produced a pressor response with a decrease in heart rate. No significant depressor response was induced by clonidine. The i.c.v. pretreatment with an AVP V₁-receptor antagonist ([d(CH₂)₅-Tyr(Me)]-AVP) at 0.5-2.5 μg dose-dependently inhibited the pressor response to 10 μg of i.c.v.-injected clonidine, while systemic (i.v.) pretreatment with the antagonist (2.5 μg) had no effect. In pentobarbital anesthetized rats, 10 μg of i.c.v.-injected clonidine caused a marked depressor response associated with bradycardia. However, i.c.v. pretreatment with the antagonist (2.5 μg) did not affect cardiovascular responses to i.c.v.-injected clonidine. These results suggest that endogenous AVP in the brain is involved in the mechanisms underlying the pressor response to i.c.v.-injected clonidine in conscious rats.