February 1, 2003Journal of Cardiovascular Pharmacology
Differences Between Angiotensin-Converting Enzyme Inhibition and Angiotensin II-AT1 Antagonism on Angiotensin-Mediated Responses in Human Internal Mammary Arteries
Why the study?
Does irbesartan or captopril more effectively inhibit Ang I-mediated contraction in human internal mammary arteries?
Population
Internal mammary arteries from 25 patients undergoing coronary bypass surgery
Comparison
Captopril with or without a chymase inhibitor… vs Control response to 10 microM phenylephrine
Design
Preclinical
Authors
Discussion
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Member takes
Implication
Ang II receptor blockade outperforms ACE inhibition in animal vessels; leaves open translation to human arteries or clinical use.
Key Points
- To compare the inhibitory efficacy of ACE inhibition versus AT1 receptor antagonism on angiotensin I-induced vasoconstriction in human internal mammary arteries.
- Assessed concentration-contraction responses to Ang I (1 nM–1 µM) in organ baths using internal mammary arteries isolated from 25 patients undergoing coronary artery bypass surgery.
- Tested vascular responses in the presence of captopril (10 µM–1 mM) with or without a chymase inhibitor (1 µM soybean trypsin inhibitor), or irbesartan (0.1 nM–1 µM), normalized against 10 µM phenylephrine controls.
- Captopril did not significantly alter the maximum contraction to Ang I compared to control conditions (43.0 ± 4.6% vs 46.3 ± 6.3%).
- Irbesartan (0.1 µM) completely abolished maximum Ang I-induced vasoconstriction, reducing response from 45.8 ± 6.7% to 1.9 ± 1.9% (p < 0.001).
- Addition of soybean trypsin inhibitor to captopril produced a significantly greater shift in -log pD2 than captopril alone (0.95 ± 0.14 vs 0.47 ± 0.06 log units, p = 0.007).
Structured PICO
Does irbesartan or captopril more effectively inhibit Ang I-mediated contraction in human internal mammary arteries?
P
Population
Internal mammary arteries from 25 patients undergoing coronary bypass surgery
I
Intervention
Captopril (10 microM-1 mM) with or without a chymase inhibitor (1 microM soybean trypsin inhibitor), or irbesartan (0.1 nM-microM)
C
Comparator
Control response to 10 microM phenylephrine
O
Outcome
Contraction responses to increasing concentrations of Ang I (1 nM-1 microM)surrogate
Angiotensin II receptor antagonism more effectively inhibits Ang I-mediated contraction in human internal mammary arteries than ACE inhibition, likely due to alternative Ang II-forming enzymes.
Cite This Study
Voors et al. (2003) studied this question.