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Transient decrease in high blood pressure by in vivo transfer of antisense oligodeoxynucleotides against rat
N Tomita1, R Morishita, J Higaki
1Department of Geriatric Medicine, Osaka (Japan) University Medical School.
Hypertension (Dallas, Tex. : 1979)
|July 1, 1995
Summary
This study shows that reducing angiotensinogen levels in hypertensive rats lowers blood pressure. Antisense oligonucleotides targeting angiotensinogen effectively decreased both angiotensinogen and angiotensin II, demonstrating its role in blood pressure regulation.
Area of Science:
- Cardiovascular Science
- Molecular Biology
- Genetics
Background:
- The renin-angiotensin system is crucial for blood pressure regulation.
- Angiotensinogen, produced in the liver, is a key substrate in this system.
- Its role as a rate-limiting factor in blood pressure and hypertension is under investigation.
Purpose of the Study:
- To investigate the hypothesis that angiotensinogen modulates blood pressure.
- To determine if targeting angiotensinogen can affect blood pressure in hypertensive models.
Main Methods:
- Antisense oligonucleotides targeting rat angiotensinogen were transfected into rat liver using liposomes.
- Delivery was facilitated by viral agglutinins for efficient cell fusion.
- Control groups received sense or scrambled oligonucleotides.
Main Results:
- Transfection of antisense oligonucleotides led to a transient decrease in plasma angiotensinogen and hepatic angiotensinogen mRNA levels.
- Plasma angiotensin II concentrations were reduced following antisense oligonucleotide treatment.
- A transient decrease in blood pressure was observed in spontaneously hypertensive rats.
Conclusions:
- Targeting angiotensinogen with antisense oligonucleotides effectively reduces its levels and associated downstream effectors.
- These findings support angiotensinogen's role in modulating blood pressure, particularly in hypertension.
- Angiotensinogen may be a viable therapeutic target for managing hypertension.