Vasoconstrictor Effect of the Angiotensin-Converting Enzyme-Resistant, Chymase-Specific Substrate [Pro11D-Ala12] Angiotensin I in Human Dorsal Hand Veins: In Vivo Demonstration of Non-ACE Production of Angiotensin II in Humans

McDonald, J. E., Padmanabhan, N., Petrie, M. C. , Hillier, C., Connell, J. M.C. and McMurray, J. J.V. (2001) Vasoconstrictor Effect of the Angiotensin-Converting Enzyme-Resistant, Chymase-Specific Substrate [Pro11D-Ala12] Angiotensin I in Human Dorsal Hand Veins: In Vivo Demonstration of Non-ACE Production of Angiotensin II in Humans. Circulation, 104(15), pp. 1805-1808. (doi:10.1161/hc4001.097220) (PMID:11591618)

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Abstract

Background: [Pro11D-Ala12] angiotensin I is an ACE-resistant substrate specific for chymase. We used this peptide to determine whether a functionally significant non-ACE angiotensin (Ang) II–generating pathway exists in human dorsal hand veins.<p></p> Methods and Results: Using a modified Aellig technique, we studied the response to Ang I and [Pro11D-Ala12] Ang I in dorsal hand veins in vivo in patients with coronary heart disease. We measured the venoconstrictor effect of each peptide given before and after a 6.25-mg oral dose of the ACE inhibitor captopril or matching placebo. Placebo or captopril was given in a double-blind, randomized fashion. Ang I induced a mean±SEM venoconstrictor response of 45±11%, 40±10%, 55±8%, and 4±4% before placebo, after placebo, before captopril, and after captopril, respectively. Hence, the response to Ang I was reproducible and was reduced significantly only after treatment with captopril (P=0.002). [Pro11D-Ala12] Ang I induced a mean venoconstrictor response of 42±9%, 49±9%, 48±10%, and 54±11% before placebo, after placebo, before captopril, and after captopril, respectively. Hence, captopril had no significant effect on the response to [Pro11D-Ala12] Ang I.<p></p> Conclusions: We have demonstrated that [Pro11D-Ala12] Ang I is able to induce venoconstriction in humans in vivo. With this specific pharmacological probe, we have shown that a non-ACE pathway capable of generating Ang II exists in human veins in vivo and is potentially functionally important. This pathway is likely to involve the enzyme chymase.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Petrie, Professor Mark and Connell, Professor John and Padmanabhan, Dr Neal and McMurray, Professor John
Authors: McDonald, J. E., Padmanabhan, N., Petrie, M. C., Hillier, C., Connell, J. M.C., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Circulation
Publisher:American Heart Association
ISSN:0009-7322
ISSN (Online):1524-4539

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