ANTISENSE INHIBITION OF AT(1) RECEPTOR MESSENGER-RNA AND ANGIOTENSINOGEN MESSENGER-RNA IN THE BRAIN OF SPONTANEOUSLY HYPERTENSIVE RATS REDUCES HYPERTENSION OF NEUROGENIC ORIGIN

Citation
R. Gyurko et al., ANTISENSE INHIBITION OF AT(1) RECEPTOR MESSENGER-RNA AND ANGIOTENSINOGEN MESSENGER-RNA IN THE BRAIN OF SPONTANEOUSLY HYPERTENSIVE RATS REDUCES HYPERTENSION OF NEUROGENIC ORIGIN, Regulatory peptides, 49(2), 1993, pp. 167-174
Citations number
27
Categorie Soggetti
Endocrynology & Metabolism
Journal title
ISSN journal
01670115
Volume
49
Issue
2
Year of publication
1993
Pages
167 - 174
Database
ISI
SICI code
0167-0115(1993)49:2<167:AIOARM>2.0.ZU;2-G
Abstract
To determine the role of angiotensinogen and angiotensin II type-i (AT (1),) receptor genes in hypertension, spontaneously hypertensive rats (SHR) were injected with synthetic antisense oligodeoxynucleotides (OD Ns), intracerebroventricularly (i.c.v). Antisense ODNs were constructe d to bases -5 to +13 of angiotensinogen mRNA (18-mer) and to bases +63 to +77 (15-mer) of angiotensin II type-1 receptor mRNA. Hypertension was significantly reduced by the application of 50 mu g of both antise nse ODNs to normotensive levels. The phosphorothioated antisense ODN t o the AT(1) receptor produced long-lasting (7 days) decreases in blood pressure. After AT(1) antisense treatment, AT(1) receptors were reduc ed in the paraventricular nucleus (PVN) and in the anterior third vent ricle area (AV3V). Following angiotensinogen antisense treatment, angi otensin II levels were significantly reduced in the brainstem (P<0.05) , indicating arrest of angiotensin II synthesis. The results demonstra te that inhibiting the brain renin-angiotensin system by antisense inh ibition of the angiotensinogen and the AT(1) receptor genes, lowers hi gh blood pressure in the SHR. The antisense administration to specific genes of the tissue renin-angiotensin system offers the possibility o f a new approach to developing antihypertension treatments.