What question did this study set out to answer?

To determine whether peripheral reduction of angiotensinogen using liposome-encapsulated antisense oligodeoxynucleotides lowers blood pressure and clarifies peripheral angiotensinogen's role in hypertension.

July 1, 1996Hypertension

Inhibition of Hypertension by Peripheral Administration of Antisense Oligodeoxynucleotides

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Why the study?

Does liposome-encapsulated antisense oligodeoxynucleotide targeted to angiotensinogen mRNA reduce blood pressure in spontaneously hypertensive rats?

Population

Spontaneously hypertensive rats

Comparison

Liposome-encapsulated antisense… vs Scrambled control oligonucleotides…

Design

Preclinical

Authors

DWDonna WielboUniversity of Florida ASAmy SimonBeam Therapeutics (United States)MPM. Ian PhillipsCalifornia Institute of Technology

Discussion

Member takes

Implication

Supports peripheral angiotensinogen targeting in experimental hypertension; leaves open translation to human therapy.

Key Points

To determine whether peripheral reduction of angiotensinogen using liposome-encapsulated antisense oligodeoxynucleotides lowers blood pressure and clarifies peripheral angiotensinogen's role in hypertension.
Evaluated sequence specificity and reduction of angiotensinogen production in vitro using cell-free translation assays.
Administered liposome-encapsulated antisense oligodeoxynucleotides intra-arterially to spontaneously hypertensive rats and tracked hepatic uptake via confocal microscopy.
Assessed blood pressure, heart rate, and plasma angiotensinogen and angiotensin II concentrations against scrambled oligonucleotides, unencapsulated antisense, and empty liposomes.
Liposome-encapsulated antisense distributed into liver tissue within 1 hour post-injection, whereas unencapsulated oligonucleotides exhibited little to no hepatic uptake.
Liposome-encapsulated antisense significantly reduced hypertensive blood pressure to normotensive levels compared with scrambled controls, unencapsulated antisense, and empty liposomes (P = .013), with no heart rate changes.
Circulating levels of peripheral angiotensinogen and angiotensin II were significantly lower in rats treated with encapsulated antisense compared to controls (P < .05).

Structured PICO

Does liposome-encapsulated antisense oligodeoxynucleotide targeted to angiotensinogen mRNA reduce blood pressure in spontaneously hypertensive rats?

Population

Spontaneously hypertensive rats

Intervention

Liposome-encapsulated antisense oligodeoxynucleotide targeted to angiotensinogen mRNA administered intra-arterially

Comparator

Scrambled control oligonucleotides, unencapsulated antisense, and empty liposomes

Outcome

Blood pressuresurrogate

Peripheral administration of liposome-encapsulated antisense oligodeoxynucleotides targeting angiotensinogen mRNA effectively lowers blood pressure in spontaneously hypertensive rats, demonstrating the role of peripheral angiotensinogen in hypertension maintenance.

Cite This Study

Wielbo et al. (1996) studied this question.

synapsesocial.com/papers/6a83077888eff2bd7befe0e7 https://doi.org/10.1161/01.hyp.28.1.147

Topics

Hypertension management

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Inhibition of Hypertension by Peripheral Administration of Antisense Oligodeoxynucleotides

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Inhibition of Hypertension by Peripheral Administration of Antisense Oligodeoxynucleotides

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

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