Angiotensin-(1-7) does not affect vasodilator or TPA responses to bradykinin in human forearm.
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.
Wilsdorf
T
T
Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6602, USA.
Gainer
J V
JV
Murphey
L J
LJ
Vaughan
D E
DE
Brown
N J
NJ
D000328:Adult; D000803:Angiotensin I / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D018709:Statistics, Nonparametric; D010959:Tissue Plasminogen Activator / Q000187:drug effects* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D014665:Vasodilator Agents; D000803:Angiotensin I; D010959:Tissue Plasminogen Activator; C118790:angiotensin I (1-7); D001920:Bradykinin