Effect of an intracerebroventricularly administered vasopressin V1 antagonist on blood pressure and heart rate in deoxycorticosterone-salt hypertensive rats.
It is well known that peripheral vasopressin (VP) is essential for the development and maintenance of DOC-salt hypertension. It is, however, still unclear whether central VP is involved in this type of hypertension. Therefore, the aim of this study was to clarify the role of central VP in the regulation of blood pressure in DOC-salt hypertension. In order to examine this issue, three series of investigations were performed. First, a novel vasopressin V1 antagonist (OPC21268) was administered intravenously to DOC-salt hypertensive rats, and mean arterial blood pressure (MABP) and heart rate (HR) were recorded. Second, the concentration of VP in the perfusate of microdialysis of cerebrospinal fluid (CSF) was determined in DOC-salt hypertensive and control rats. Finally, intracerebroventricular (i.c.v.) administration of a V1 antagonist was performed in DOC-salt hypertensive rats to determine the central mechanism of hypertension. Intravenous administration of a V1 antagonist had no effect on MABP and HR. There was no difference in VP in the perfusate of CSF between DOC-salt hypertensive and control rats. I.c.v. administration of a V1 antagonist significantly decreased MABP and HR in a dose-dependent manner in DOC-salt hypertensive rats (P < 0.05-0.01). These results suggest that central VP is involved in the maintenance of DOC-salt hypertension, and the mechanism is, in part, mediated by upregulation of the V1 receptor.
Toba
K
K
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Ouchi
Y
Y
Liang
J
J
Akishita
M
M
Orimo
H
H
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D010880:Piperidines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D065092:Antidiuretic Hormone Receptor Antagonists; D010880:Piperidines; D015363:Quinolones; C068644:OPC 21268; D003900:Desoxycorticosterone