What question did this study set out to answer?

To determine the role of the bradykinin-nitric oxide pathway in mediating the protective effects of the ACE inhibitor imidapril against inflammatory vascular injury.

September 9, 2003Hypertension

Important Role of Nitric Oxide in the Effect of Angiotensin-Converting Enzyme Inhibitor Imidapril on Vascular Injury

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Why the study?

Does imidapril reduce inflammatory vascular injury and neointimal formation in a mouse model of femoral artery cuff placement?

Key Points

To determine the role of the bradykinin-nitric oxide pathway in mediating the protective effects of the ACE inhibitor imidapril against inflammatory vascular injury.
Placed a polyethylene cuff around the femoral artery of AT1a-receptor-deficient (AT1aKO) and wild-type (C57BL/6J) mice to induce inflammatory vascular injury.
Administered a blood pressure-neutral low dose of imidapril (1 mg/kg per day) via gavage, with or without the bradykinin antagonist Hoechst 140 or the nitric oxide synthase inhibitor L-NAME.
Measured neointimal area at 14 days post-cuff placement and assessed smooth muscle cell proliferation, cGMP levels, and MCP-1/TNF-alpha expression at 7 days.
Imidapril significantly attenuated neointimal formation, smooth muscle cell DNA synthesis, and MCP-1/TNF-alpha expression in both wild-type and AT1aKO mice without altering systemic blood pressure.
Imidapril significantly increased tissue cGMP content after arterial injury without altering AT2 receptor or ACE expression.
Co-administration of Hoechst 140 or L-NAME abolished the vascular protective and anti-inflammatory effects of imidapril in both wild-type and AT1aKO mice.

Structured PICO

Does imidapril reduce inflammatory vascular injury and neointimal formation in a mouse model of femoral artery cuff placement?

Population

AT1a-receptor-deficient (AT1aKO) mice and wild-type (WT; C57BL/6J) mice with a polyethylene cuff placed around the femoral artery to induce inflammatory vascular injury

Intervention

Imidapril (1 mg/kg per day) administered by gavage

Comparator

Control mice (implied) and mice treated with imidapril plus a bradykinin receptor antagonist (Hoechst 140) or an NO synthase inhibitor (L-NAME)

Outcome

Neointimal area in cross sections of the artery measured 14 days after cuff placementsurrogate

The beneficial effects of imidapril on vascular remodeling involve activation of the bradykinin-NO system in addition to angiotensin II blockade.

Discussion

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Implication

Hypothesis-generating for bradykinin-NO contribution to ACEI vascular effects in mice; leaves open human translation.

Cite This Study

Chen et al. (2003) studied this question.

synapsesocial.com/papers/6a8b2c3ef71b672e3df46e87 https://doi.org/10.1161/01.hyp.0000092440.52239.39

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Important Role of Nitric Oxide in the Effect of Angiotensin-Converting Enzyme Inhibitor Imidapril on Vascular Injury

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Important Role of Nitric Oxide in the Effect of Angiotensin-Converting Enzyme Inhibitor Imidapril on Vascular Injury

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider