Vasoconstrictor Effect of the Angiotensin-Converting Enzyme–Resistant, Chymase-Specific Substrate Pro 11 D -Ala 12 Angiotensin I in Human Dorsal Hand Veins
Key result
Captopril significantly reduced the venoconstrictor response to Ang I (4% vs 40% after placebo, P=0.002) but had no significant effect on the response to [Pro(11)(D)-Ala(12)] Ang I.
Why the study?
Does [Pro11D-Ala12] Angiotensin I induce venoconstriction via a non-ACE pathway in patients with coronary heart disease?
Population
Patients with coronary heart disease
Comparison
[Pro11D-Ala12] Angiotensin I and Angiotensin I… vs Matching placebo
Design
RCT, randomized fashion, double-blind
Authors
Discussion
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Implication
Non-ACE pathways mediate venoconstriction in CHD patients; extends evidence for alternative Ang II generation in vivo.
Key Points
- To determine whether a functionally significant non-angiotensin-converting enzyme (ACE) pathway, specifically mediated by chymase, generates angiotensin II and causes venoconstriction in human dorsal hand veins in vivo.
- Conducted a double-blind, randomized trial evaluating dorsal hand vein responses in vivo using a modified Aellig technique in patients with coronary heart disease.
- Measured venoconstrictor responses to local infusions of angiotensin I and the chymase-specific substrate [Pro11(D)-Ala12] angiotensin I before and after a 6.25-mg oral dose of captopril or matching placebo.
- Angiotensin I induced a mean±SEM venoconstriction of 55±8% before captopril versus 4±4% after captopril (P=0.002), while placebo showed no significant change (45±11% before vs. 40±10% after).
- [Pro11(D)-Ala12] angiotensin I induced venoconstriction that was unaffected by captopril (48±10% before vs. 54±11% after) or placebo (42±9% before vs. 49±9% after).
Study Design
Type
RCT
Blinding
Double-blind
Randomization
Randomized
Structured PICO
Does [Pro11D-Ala12] Angiotensin I induce venoconstriction via a non-ACE pathway in patients with coronary heart disease?
P
Population
Patients with coronary heart disease undergoing in vivo dorsal hand vein response testing.
I
Intervention
[Pro11D-Ala12] Angiotensin I and Angiotensin I administered before and after a 6.25-mg oral dose of captopril
C
Comparator
Matching placebo
O
Outcome
Venoconstrictor effect in dorsal hand veinssurrogate
Main Result
Absolute Event Rate: 4% vs 40%
p-value: p=0.002
A non-ACE pathway, likely involving chymase, is capable of generating Angiotensin II and inducing venoconstriction in human veins in vivo.
Cite This Study
McDonald et al. (2001) conducted an RCT in Coronary heart disease. Captopril vs. Placebo was evaluated on Venoconstrictor response to Ang I and [Pro(11)(D)-Ala(12)] Ang I (p=0.002). Captopril significantly reduced the venoconstrictor response to Ang I (4% vs 40% after placebo, P=0.002) but had no significant effect on the response to [Pro(11)(D)-Ala(12)] Ang I.