Vasoconstrictor effect of the angiotensin converting enzyme resistant, chymase specific, substrate [Pro11 D-Ala12] angiotensin I in human dorsal hand veins: in vivo demonstration of non-ACE production of angiotensin II in humans

John E. McDonald, Neal Padmanabhan, Mark C. Petrie, Chris Hillier, John M.C. Connell, John J.V. McMurray

Research output: Contribution to journalArticle

Abstract

[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. 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. 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.

Original languageEnglish
Pages (from-to)1805-1808
Number of pages4
JournalCirculation
Volume104
Issue number15
DOIs
Publication statusPublished - 1 Oct 2001

Keywords

  • vasoconstriction
  • angiotensin
  • peptides
  • enzymes
  • veins

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