Document Detail

Antisense inhibition of angiotensinogen attenuates vasopressin release in the paraventricular hypothalamic nucleus of spontaneously hypertensive rats.
MedLine Citation:
PMID:  10350537     Owner:  NLM     Status:  MEDLINE    
It has been reported that intracerebroventricularly injected antisense oligonucleotide to angiotensinogen reduces arterial pressure in spontaneously hypertensive rats (SHR), but the mechanism and the sites of action remain unclear. In the present study, we examined whether injection of antisense oligonucleotide to angiotensinogen into the paraventricular hypothalamic nucleus (PVN) would influence arterial pressure and vasopressin release. For this purpose, 12-week-old male SHR were cannulated into the bilateral PVN. One week later, we injected antisense or sense oligonucleotide to angiotensinogen into the bilateral PVN (0.2 nmol/200 nl each side). After 24 h, we directly monitored arterial pressure, and then took blood samples to measure plasma vasopressin, catecholamines and renin activity. Mean arterial pressure did not change in either group (from 144+/-3 to 154+/-4 mmHg for the antisense oligonucleotide group, n=11; from 147+/-4 to 156+/-3 mmHg for the sense oligonucleotide group, n=11). Antisense oligonucleotide attenuated vasopressin release compared with sense oligonucleotide (1.30+/-0.28 vs. 3.29+/-0.60 pg/ml, respectively, P<0.01). Plasma catecholamines also decreased in the antisense oligonucleotide group compared with the sense oligonucleotide group. However, the plasma renin activity did not differ between the groups. In the additional experiment, we examined the neurohormonal and cardiovascular effects of intracerebroventricularly injected antisense oligonucleotide to angiotensinogen in SHR. Mean arterial pressure, plasma vasopressin and plasma norepinephrine were significantly lower in the antisense oligonucleotide group than in the sense oligonucleotide group. These results suggest that angiotensinogen in PVN plays important roles in vasopressin release and sympathetic nerve activity, but may not contribute to the maintenance of arterial pressure in SHR.
S Kagiyama; T Tsuchihashi; I Abe; K Matsumura; M Fujishima
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Brain research     Volume:  829     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-08-02     Completed Date:  1999-08-02     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  120-4     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Elsevier Science B.V.
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
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MeSH Terms
Angiotensinogen / genetics*
Hypertension / physiopathology*
Injections, Intraventricular
Oligonucleotides / pharmacology
Oligonucleotides, Antisense / pharmacology*
Paraventricular Hypothalamic Nucleus / drug effects*,  secretion
Rats, Inbred SHR
Secretory Rate / drug effects
Vasopressins / secretion*
Reg. No./Substance:
0/Oligonucleotides; 0/Oligonucleotides, Antisense; 11000-17-2/Vasopressins; 11002-13-4/Angiotensinogen

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