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(Hypertension. 2001;37:1136.)
© 2001 American Heart Association, Inc.

Scientific Contributions

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

From the Divisions of Cardiovascular Medicine (T.W., D.E.V.) and Clinical Pharmacology (J.V.G., L.J.M., N.J.B.), Vanderbilt University Medical Center, Nashville, Tenn.

Correspondence to Nancy J. Brown, MD, 560 MRB I, Vanderbilt University Medical Center, Nashville, TN 37232-6602. E-mail nancy.brown{at}mcmail.vanderbilt.edu

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.

Key Words: angiotensin • angiotensin-converting enzyme • bradykinin • endothelium • plasminogen • vasodilator agents

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