What is the clinical evidence from this study?

Study design: Other. Population: Aldosterone/salt-induced hypertension (n=38). Intervention: Spironolactone vs. Vehicle (aldosterone + 1% NaCl). Primary outcome: Perivascular fibrosis (p=<0.01).

What question did this study set out to answer?

To determine whether ACE/EGFR/ERK, NAD(P)H oxidase/LOX-1, and Rho-kinase signaling pathways drive cardiovascular remodeling in aldosterone/salt-induced hypertension and whether spironolactone attenuates this damage.

January 1, 2005Hypertension ResearchOpen Access

Cardioprotective Mechanisms of Spironolactone Associated with the Angiotensin-Converting Enzyme/Epidermal Growth Factor Receptor/Extracellular Signal-Regulated Kinases, NAD(P)H Oxidase/Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1, and Rho-Kinase Pathways in Aldosterone/Salt-Induced Hypertensive Rats

Q: What are the key findings of this study?

Spironolactone significantly reduced perivascular fibrosis (0.33 vs 0.52) and wall-to-lumen ratio (0.17 vs 0.25) compared to vehicle in aldosterone/salt-induced hypertensive rats.

Q: What question did this study set out to answer?

To determine whether ACE/EGFR/ERK, NAD(P)H oxidase/LOX-1, and Rho-kinase signaling pathways drive cardiovascular remodeling in aldosterone/salt-induced hypertension and whether spironolactone attenuates this damage.

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Key result

Spironolactone significantly reduced perivascular fibrosis (0.33 vs 0.52) and wall-to-lumen ratio (0.17 vs 0.25) compared to vehicle in aldosterone/salt-induced hypertensive rats.

Why the study?

Does spironolactone prevent cardiovascular remodeling in aldosterone/salt-induced hypertensive rats?

Population

6-week-old male normotensive Wistar rats (n=44 total; 38 in main experiment, 6 in supplemental experiment)

Comparison

Spironolactone added to drinking solution, in… vs 1% NaCl plus vehicle and 1% NaCl plus aldosterone

Design

Preclinical, randomly divided into six groups

Follow-up

6 weeks

Authors

SNShigefumi NakanoDokkyo University NKNaohiko KobayashiMatsumoto Livestock Hygiene Service Center KYKohtaro YoshidaNagaoka Red Cross Hospital

Discussion

Member takes

Implication

Spironolactone attenuates vascular remodeling in this aldosterone/salt rat model; hypothesis-generating for human cardiovascular protection trials.

Key Points

To determine whether ACE/EGFR/ERK, NAD(P)H oxidase/LOX-1, and Rho-kinase signaling pathways drive cardiovascular remodeling in aldosterone/salt-induced hypertension and whether spironolactone attenuates this damage.
Assigned Wistar rats receiving 1% NaCl drinking water to 6-week treatment groups: vehicle, aldosterone (0.75 μg/h), aldosterone plus spironolactone (20 mg/kg/day), aldosterone plus imidapril (1 mg/kg/day), aldosterone plus apocynin (0.5 mmol/L), or aldosterone plus Y-27632 (3 mg/kg/day).
Assessed vascular lesion formation, medial thickness, perivascular fibrosis, and expression levels of target pathway proteins and mRNA markers (TGF-β1, collagens I/III, and MCP-1).
Spironolactone and pathway-selective inhibitors significantly suppressed aldosterone-induced ACE/EGFR upregulation, p44/p42ERK phosphorylation, NAD(P)H oxidase and LOX-1 expression, and RhoA/Rho-kinase activation.
Treatment with spironolactone effectively inhibited vascular lesion formation, medial wall thickening, perivascular fibrosis, and the elevated expression of TGF-β1, type I and III collagen, and MCP-1 mRNA.

Structured PICO

Does spironolactone prevent cardiovascular remodeling in aldosterone/salt-induced hypertensive rats?

Population

38 6-week-old male Wistar rats with aldosterone/salt-induced hypertension treated for 6 weeks.

Intervention

Spironolactone (20 mg/kg/day) added to drinking solution, in combination with 1% NaCl and aldosterone (0.75 microg/h, s.c.) for 6 weeks

Comparator

1% NaCl plus vehicle (CON) and 1% NaCl plus aldosterone (ALD-V)

Outcome

Cardiovascular remodeling (wall-to-lumen ratio, perivascular fibrosis) and expression of ACE, EGFR, NAD(P)H oxidase subunits, LOX-1, RhoA, Rho-kinase, and phosphorylation of p44/p42ERK, p70S6K, MLCsurrogate

Main Result

Absolute Event Rate: 0.33% vs 0.52%

p-value: p=<0.01

Spironolactone prevents cardiovascular remodeling in aldosterone/salt-induced hypertensive rats by suppressing the ACE/EGFR/ERK, NAD(P)H oxidase/LOX-1, and Rho-kinase pathways.

Limitations

Difficult to determine which pathway is the most important or if every pathway is involved to a similar degree
Animal model results may not directly translate to humans

Cite This Study

Nakano et al. (2005) studied Aldosterone/salt-induced hypertension (n=38). Spironolactone vs. Vehicle (aldosterone + 1% NaCl) was evaluated on Perivascular fibrosis (p=<0.01). Spironolactone significantly reduced perivascular fibrosis (0.33 vs 0.52) and wall-to-lumen ratio (0.17 vs 0.25) compared to vehicle in aldosterone/salt-induced hypertensive rats.

synapsesocial.com/papers/6a7070f45671bbf00bc2b399 https://doi.org/10.1291/hypres.28.925

Topics

Hypertension management

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Implication

Spironolactone attenuates vascular remodeling in this aldosterone/salt rat model; hypothesis-generating for human cardiovascular protection trials.

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Topics

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Topics

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