What is the clinical evidence from this study?

Intervention: Amlodipine combined with ramiprilat vs. Ramiprilat alone. Primary outcome: Nitrite release (pmol/mg) (p=< 0.05).

What question did this study set out to answer?

To determine whether amlodipine potentiates nitric oxide production during angiotensin-converting enzyme (ACE) inhibition in coronary microvessels and to assess the kinin-dependent pathways involved.

February 1, 2000Journal of Cardiovascular Pharmacology

Amlodipine Enhances NO Production Induced by an ACE Inhibitor Through a Kinin-Mediated Mechanism in Canine Coronary Microvessels

Q: What are the key findings of this study?

Amlodipine significantly enhanced nitrite release induced by ramiprilat from 122 +/- 9 to 168 +/- 14 pmol/mg (p < 0.05) in canine coronary microvessels.

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

To determine whether amlodipine potentiates nitric oxide production during angiotensin-converting enzyme (ACE) inhibition in coronary microvessels and to assess the kinin-dependent pathways involved.

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Key result

Amlodipine significantly enhanced nitrite release induced by ramiprilat from 122 +/- 9 to 168 +/- 14 pmol/mg (p < 0.05) in canine coronary microvessels.

Why the study?

Does amlodipine combined with an ACE inhibitor enhance NO production in canine coronary microvessels compared to ACE inhibition alone?

Population

Coronary microvessels isolated from 16 mongrel dogs

Comparison

Amlodipine combined with ramiprilat vs Ramiprilat (10^-7 M) alone

Design

Preclinical

Authors

XZXiaoping ZhangUnion Hospital XXXiaobin XuBeijing University of Technology ANAlberto NasjlettiNew York Medical College

Discussion

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Implication

May enhance NO with ACE inhibitors in vitro; leaves open in vivo relevance or clinical effects.

Key Points

To determine whether amlodipine potentiates nitric oxide production during angiotensin-converting enzyme (ACE) inhibition in coronary microvessels and to assess the kinin-dependent pathways involved.
Isolated coronary microvessels from 16 mongrel dogs.
Quantified nitrite release (a marker of nitric oxide) using the Griess reaction following treatment with bradykinin, kallikrein, ramiprilat, and amlodipine.
Assessed mechanistic pathways by co-administering L-NAME (nitric oxide synthase inhibitor), HOE 140 (B2-kinin receptor antagonist), and DCIC (serine protease inhibitor blocking kinin synthesis).
Amlodipine (10⁻¹⁰ M) significantly enhanced ramiprilat (10⁻⁷ M)-induced nitrite release from 122 ± 9 to 168 ± 14 pmol/mg (p < 0.05 vs. ramiprilat).
Potentiated nitrite release from the combination of ramiprilat and amlodipine was entirely blocked by L-NAME, HOE 140, and DCIC.

Structured PICO

Does amlodipine combined with an ACE inhibitor enhance NO production in canine coronary microvessels compared to ACE inhibition alone?

Population

Coronary microvessels isolated from 16 mongrel dogs to study NO formation.

Intervention

Amlodipine (10^-10 M) combined with ramiprilat (10^-7 M)

Comparator

Ramiprilat (10^-7 M) alone

Outcome

Nitrite release (hydration product of NO) quantified by the Griess reactionsurrogate

Main Result

Absolute Event Rate: 168% vs 122%

p-value: p=< 0.05

Amlodipine synergistically enhances NO production when combined with an ACE inhibitor in canine coronary microvessels via a kinin-mediated mechanism.

Cite This Study

Zhang et al. (2000) studied this question. Amlodipine combined with ramiprilat vs. Ramiprilat alone was evaluated on Nitrite release (pmol/mg) (p=< 0.05). Amlodipine significantly enhanced nitrite release induced by ramiprilat from 122 +/- 9 to 168 +/- 14 pmol/mg (p < 0.05) in canine coronary microvessels.

synapsesocial.com/papers/6a6cfa5731a3df824326de44 https://doi.org/10.1097/00005344-200002000-00004

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Amlodipine Enhances NO Production Induced by an ACE Inhibitor Through a Kinin-Mediated Mechanism in Canine Coronary Microvessels

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Amlodipine Enhances NO Production Induced by an ACE Inhibitor Through a Kinin-Mediated Mechanism in Canine Coronary Microvessels

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

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