What question did this study set out to answer?

To determine the relative functional contributions and local conversion efficiency of ACE and chymase in generating angiotensin II from angiotensin I in human coronary arteries.

February 1, 2003Arteriosclerosis Thrombosis and Vascular BiologyOpen Access

ACE- Versus Chymase-Dependent Angiotensin II Generation in Human Coronary Arteries

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Population

Human coronary artery (HCA) rings and perfused segments

Comparison

Angiotensin I, PA-angiotensin I, and specific… vs Angiotensin II and uninhibited states

Design

Preclinical

Authors

BTBeril TomLifeline Hospital IGIngrid M. GarreldsErasmus MC ESElizabeth ScalbertServier (France)

Discussion

Member takes

Implication

Dual ACE/chymase inhibition may enhance coronary angiotensin II suppression; leaves open clinical translation in human disease.

Key Points

To determine the relative functional contributions and local conversion efficiency of ACE and chymase in generating angiotensin II from angiotensin I in human coronary arteries.
Mounted human coronary artery rings in organ baths to measure vasoconstrictor concentration-response curves to angiotensin II, angiotensin I, and the chymase-selective substrate PA-angiotensin I.
Evaluated enzymatic contributions using pharmacological inhibition with captopril (ACE inhibitor), C41, and chymostatin (chymase inhibitors) in both isolated rings and perfused arterial segments.
Single inhibition of ACE or chymase shifted the angiotensin I concentration-response curve approximately 5-fold rightward, whereas combined inhibition induced an approximate 10-fold rightward shift.
Chymostatin abolished PA-angiotensin I-induced vasoconstriction and suppressed bath angiotensin II levels, whereas captopril and C41 did not decrease bath peptide concentrations.
Angiotensin I application to perfused arterial segments elicited luminal and adventitial release of angiotensin II that was completely blocked by chymostatin.

Structured PICO

Population

Human coronary artery (HCA) rings and perfused segments

Intervention

Angiotensin I, PA-angiotensin I, and specific inhibitors (captopril for ACE, C41 or chymostatin for chymase)

Comparator

Angiotensin II and uninhibited states

Outcome

Vasoconstriction and angiotensin II generation (interstitial and bath levels)surrogate

Both ACE and chymase contribute to functionally active angiotensin II generation in human coronary arteries, but ACE-mediated conversion occurs more efficiently closer to AT1 receptors.

Cite This Study

Tom et al. (2003) studied this question.

synapsesocial.com/papers/6a719c58f44fa9f079df6073 https://doi.org/10.1161/01.atv.0000051875.41849.25

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ACE- Versus Chymase-Dependent Angiotensin II Generation in Human Coronary Arteries

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

ACE- Versus Chymase-Dependent Angiotensin II Generation in Human Coronary Arteries

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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