Abstract:
:In this study, we evaluated the bradykinin potentiating activity and ACE inhibitory activity of several Ang-(1-7)-related peptides: Ang-(2-7), Ang-(3-7), Ang-(4-7), Ang-(1-6), Ang-(1-5) and the selective antagonist of Ang-(1-7): D-[Ala7]Ang-(1-7) (A-779). In vivo experiments were performed in freely moving Wistar rats. ACE activity was evaluated by a fluorometric assay in rat plasma using Hip-His-Leu as a substrate. Intravenous injections of Ang-(1-7) (2.2 nmol) transformed the effect of a single dose of bradykinin (1 nmol) into the effect produced by a double dose. A similar bradykinin potentiating activity was demonstrated for Ang-(2-7) and Ang-(3-7). On the other hand, Ang-(1-5), Ang-(1-6), Ang-(4-7) and A-779 did not change the hypotensive effect of bradykinin in doses ranging from 8 up to 25 nmols. The hypotensive effect of bradykinin was increased by intravenous infusion (0.3 ng/min) of Ang-(1-7) > Ang-(2-7) > Ang-(3-7). Conversely, Ang-(1-5), Ang-(1-6), Ang-(4-7) or A-779 did not change the hypotensive effect of bradykinin. ACE inhibition with Ang-(1-7) related peptides occurred in the order: Ang-(2-7) > or = Ang-(3-7) > Ang-(1-7) [>] Ang-(1-5) > Ang-(4-7) > or = Ang-(1-6) > or = A-779. A-779 in concentrations up to 10(-5) M did not change the ACE inhibitory activity of Ang-(1-7). These results suggest that Ang-(1-7), Ang-(2-7) and Ang-(3-7) can modulate bradykinin actions in vivo. More important, our data pointed out that alternative mechanisms besides interaction with ACE are required to explain the bradykinin potentiating activity of Ang-(1-7).
journal_name
Peptidesjournal_title
Peptidesauthors
Paula RD,Lima CV,Britto RR,Campagnole-Santos MJ,Khosla MC,Santos RAdoi
10.1016/s0196-9781(99)00031-5subject
Has Abstractpub_date
1999-01-01 00:00:00pages
493-500issue
4eissn
0196-9781issn
1873-5169pii
S0196-9781(99)00031-5journal_volume
20pub_type
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