Tallant EA, Lu X, Weiss RB, Chappell MC, Ferrario CM
Endothelial cells contain a novel angiotensin (1-7)
binding site
50th Annual Fall Conference AHA Council for High Blood Pressure
Research
Hypertens
(Sep) 28:511 1996
Angiotensin 1-7 (Ang 1-7, derived from Ang I) has been shown to potentiate
the hypotensive effect of bradykinin (BK) in vivo. These studies, in
cultured bovine aortic endothelial cells (which do not express message for
either AT1 or AT2 receptors) were designed to find novel, high affinity
binding sites which might mediate specific Ang 1-7 effects, possibly by
leading to release of endothelium-derived vasodilators. Iodinated Ang 1-7
bound to two sites on endothelial cells, one with an affinity of 8.2 nM that
demonstrated saturable binding at 276 fmol/mg protein. This binding was not
affected by AT1 or AT2 receptor antagonists and Ang II interacted only
weakly with this site. D-[Ala]7-Ang -7 blocked Ang 1-7 binding with an IC50
of 106 nM, suggesting it may be a useful antagonist for future
pharmacological studies.
Comment: Ang 1-7, one of a growing list of angiotensin-derived
peptides appears to
have a specific high affinity binding site on endothelial cells which may
mediate its pharmacologic effects, including vasodilation and potentiation
of BK effects.
Jason G. Umans, M.D., University of Chicago
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50th Annual Fall Conference AHA Council for High Blood Pressure
Research
H: Pathophysiology :
Endothelium, Nitric Oxide