Intracerebroventricular treatment with vasopressin V1-receptor antagonist inhibits centrally-mediated pressor response to clonidine in conscious rats.
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 micrograms) 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 micrograms dose-dependently inhibited the pressor response to 10 micrograms of i.c.v.-injected clonidine, while systemic (i.v.) pretreatment with the antagonist (2.5 micrograms) had no effect. In pentobarbital-anesthetized rats, 10 micrograms of i.c.v.-injected clonidine caused a marked depressor response associated with bradycardia. However, i.c.v. pretreatment with the antagonist (2.5 micrograms) 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.
Nakamura
S
S
Department of Pharmacology, Miyazaki Medical College, Japan.
Kawasaki
H
H
Takasaki
K
K
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D003000:Clonidine