What does this research mean for the field?

Angiotensin II induces vascular smooth muscle cell hypertrophy through the AT1 receptor-mediated activation of NADH/NADPH oxidase, which generates superoxide that is subsequently converted into H2O2, a critical mediator of the hypertrophic response. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine whether angiotensin II activation of NADH/NADPH oxidase generates hydrogen peroxide and to evaluate the functional role of this pathway in vascular smooth muscle cell hypertrophy.

September 1, 1998Hypertension

Role of NADH/NADPH Oxidase–Derived H2O2in Angiotensin II–Induced Vascular Hypertrophy

View Full Paper

Ask AI

Bookmark

Population

Vascular smooth muscle cells, including wild-type cells, cells stably transfected with antisense p22phox…

Comparison

Angiotensin II (100 nmol/L) vs Untreated cells and cells treated with inhibitors

Design

Preclinical

Follow-up

4 hours

Authors

AZA. Maziar ZafariEmory University MUMasuko Ushio‐FukaiVascular / Pulmonary Vascular MAMarjorie AkersEmory University

Discussion

Member takes

Overview

Hypothesis-generating in animal VSMC; leaves open H2O2 pathway relevance to human hypertension.

Key Points

To determine whether angiotensin II activation of NADH/NADPH oxidase generates hydrogen peroxide and to evaluate the functional role of this pathway in vascular smooth muscle cell hypertrophy.
Treated cultured vascular smooth muscle cells with angiotensin II (100 nmol/L) and evaluated intracellular hydrogen peroxide accumulation alongside superoxide dismutase and catalase activities.
Assessed oxidase dependency and hypertrophy mechanisms using pharmacologic inhibitors (losartan, diphenylene iodonium, extracellular catalase, diethylthiocarbamate) and stable genetic cell lines (antisense p22phox and catalase overexpression).
Angiotensin II significantly increased intracellular hydrogen peroxide levels at 4 hours without altering endogenous superoxide dismutase or catalase activity.
Hydrogen peroxide generation was blocked by losartan, diphenylene iodonium, extracellular catalase, and antisense p22phox transfection.
Hypertrophy was markedly suppressed in cells overexpressing catalase and in cells treated with the superoxide dismutase inhibitor diethylthiocarbamate (1 mmol/L), which produced 62 ± 2% inhibition.

Structured PICO

Population

Vascular smooth muscle cells (VSMCs), including wild-type cells, cells stably transfected with antisense p22phox, and a novel cell line stably overexpressing catalase

Intervention

Angiotensin II (100 nmol/L)

Comparator

Untreated cells and cells treated with inhibitors (extracellular catalase, diphenylene iodonium, losartan, or diethylthiocarbamate)

Outcome

Intracellular H2O2 generation, intracellular superoxide dismutase and catalase activity, and cellular hypertrophysurrogate

Angiotensin II induces vascular smooth muscle cell hypertrophy via AT1 receptor-mediated production of superoxide by NADH/NADPH oxidase, which is subsequently converted to intracellular H2O2.

Cite This Study

Zafari et al. (1998) studied this question.

synapsesocial.com/papers/6a1d237d73c56dd1bd2f3fac https://doi.org/10.1161/01.hyp.32.3.488

View Full Paper

Ask AI

Bookmark

September 1, 1998Hypertension

Role of NADH/NADPH Oxidase–Derived H2O2in Angiotensin II–Induced Vascular Hypertrophy

View Full Paper

Ask AI

Bookmark

Population

Vascular smooth muscle cells, including wild-type cells, cells stably transfected with antisense p22phox…

Comparison

Angiotensin II (100 nmol/L) vs Untreated cells and cells treated with inhibitors

Design

Preclinical

Follow-up

4 hours

Authors

AZA. Maziar ZafariEmory University MUMasuko Ushio‐FukaiVascular / Pulmonary Vascular MAMarjorie AkersEmory University

Discussion

Member takes

Overview

Hypothesis-generating in animal VSMC; leaves open H2O2 pathway relevance to human hypertension.

Key Points

To determine whether angiotensin II activation of NADH/NADPH oxidase generates hydrogen peroxide and to evaluate the functional role of this pathway in vascular smooth muscle cell hypertrophy.
Treated cultured vascular smooth muscle cells with angiotensin II (100 nmol/L) and evaluated intracellular hydrogen peroxide accumulation alongside superoxide dismutase and catalase activities.
Assessed oxidase dependency and hypertrophy mechanisms using pharmacologic inhibitors (losartan, diphenylene iodonium, extracellular catalase, diethylthiocarbamate) and stable genetic cell lines (antisense p22phox and catalase overexpression).
Angiotensin II significantly increased intracellular hydrogen peroxide levels at 4 hours without altering endogenous superoxide dismutase or catalase activity.
Hydrogen peroxide generation was blocked by losartan, diphenylene iodonium, extracellular catalase, and antisense p22phox transfection.
Hypertrophy was markedly suppressed in cells overexpressing catalase and in cells treated with the superoxide dismutase inhibitor diethylthiocarbamate (1 mmol/L), which produced 62 ± 2% inhibition.

Structured PICO

Population

Vascular smooth muscle cells (VSMCs), including wild-type cells, cells stably transfected with antisense p22phox, and a novel cell line stably overexpressing catalase

Intervention

Angiotensin II (100 nmol/L)

Comparator

Untreated cells and cells treated with inhibitors (extracellular catalase, diphenylene iodonium, losartan, or diethylthiocarbamate)

Outcome

Intracellular H2O2 generation, intracellular superoxide dismutase and catalase activity, and cellular hypertrophysurrogate

Angiotensin II induces vascular smooth muscle cell hypertrophy via AT1 receptor-mediated production of superoxide by NADH/NADPH oxidase, which is subsequently converted to intracellular H2O2.

Cite This Study

Zafari et al. (1998) studied this question.

synapsesocial.com/papers/6a1d237d73c56dd1bd2f3fac https://doi.org/10.1161/01.hyp.32.3.488

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

View Full Paper

Ask AI

Bookmark