Angiotensin-(1-7) does not affect vasodilator or TPA responses to bradykinin in human forearm

Terry Wilsdorf, James V. Gainer, Laine J. Murphey, Douglas E. Vaughan, Nancy J. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Studies in isolated vessels and rat models of hypertension suggest that angiotensin (Ang)-(1-7) potentiates the vasodilator effect of bradykinin, possibly through ACE inhibition. We therefore tested the hypothesis that Ang-(1-7) potentiates the vasodilator or tissue plasminogen activator (TPA) response to bradykinin in the human forearm vasculature. Graded doses of Ang-(1-7) (10, 100, and 300 pmol/min), bradykinin (47, 94, and 189 pmol/min), and Ang I (1, 10, and 30 pmol/min) were administered through the brachial artery to 8 normotensive subjects in random order. Thirty minutes after initiation of a constant infusion of Ang-(1-7) (100 pmol/min), bradykinin and Ang I infusions were repeated. There were no systemic hemodynamic effects of the agonists. Bradykinin significantly increased forearm blood flow (P<0.001, from 3.8±0.5 to 13.9±3.1 mL/min per 100 mL at 189 pmol/min) and net TPA release (P=0.007, from 1.1±1.0 to 23.6±6.2 ng/min per 100 mL at 189 pmol/min), whereas Ang I caused vasoconstriction (P=0.003, from 3.3±0.4 to 2.5±0.3 mL/min per 100 mL at 30-pmol/min dose). There was no effect of Ang-(1-7) on either forearm blood flow (P=0.62, 3.3±0.4 to 3.5+0.4 mL/min per 100 mL at 300 pmol/min) or TPA release (P=0.52, from 0.7±0.8 to 1.0±0.7 ng/min/100 mL at 300 pmol/min). Moreover, there was no effect of 100 pmol/min Ang-(1-7) on the vasodilator [P=0.46 for Ang-(1-7) effect] or TPA [P=0.82 for Ang-(1-7) effect] response to bradykinin or the vasoconstrictor response to Ang I [P=0.62 for Ang-(1-7) effect]. These data do not support a role of Ang-(1-7), given at supraphysiological doses, in the regulation of human peripheral vascular resistance or fibrinolysis.

Original languageEnglish (US)
Pages (from-to)1136-1140
Number of pages5
JournalHypertension
Volume37
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Angiotensin
  • Angiotensin-converting enzyme
  • Bradykinin
  • Endothelium
  • Plasminogen
  • Vasodilator agents

ASJC Scopus subject areas

  • Internal Medicine

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