Vasodilator effect of angiotensin-(1-7) in mature and sponge-induced neovasculature.
Angiotensin-(1-7) (Ang-(1-7)), a peptide constituent of the renin-angiotensin system, has been shown to act as a vasodilator mediator in pre-existing (skin) and newly formed vasculatures (14-day-old sponge implants). Blood flow was determined by the outflow rate of sodium fluorescein applied intradermally or intraimplant and the results were expressed in t(1/2) values (time taken for the fluorescence to reach 50% of the peak in the systemic circulation). We showed that the t(1/2) value was significantly lower (4.1+/-0.46) in the implants compared with the cutaneous vasculature (5.7+/-0.5). Ang-(1-7) 20 ng was able to decrease t(1/2) values in both vasculatures. The specific receptor antagonist, D-Ala7-Ang-(1-7) (A-779), prevented Ang-(1-7)-induced vasodilation and altered the basal vascular tone of the implants. The vasodilator effect was also abolished by nitric oxide (NO) synthase inhibitors in both vasculatures and by indomethacin in the implant. Selective AT(1) and AT(2) receptor antagonists did not alter the vasodilation induced by the peptide. These results establish the vasodilator effect of Ang-(1-7) in the cutaneous and implant vasculature and that the peptide is produced endogenously by the fibrovascular tissue, and suggest that this peptide contributes for the vasodilation found in newly formed vascular beds (wound healing, chronic inflammatory processes and tumors).
Machado
R D P
RD
Department of Physiology and Biophysics, Federal University of Minas Gerais, Av. Antônio Carlos 6627, Campus Pampulha, Cx. Post. 486, 31270-901, Belo Horizonte, Brazil.
Ferreira
M A N D
MA
Belo
A V
AV
Santos
R A S
RA
Andrade
S P
SP
D000803:Angiotensin I / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019793:Fluorescein / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*; D015503:Surgical Sponges; D014018:Tissue Distribution; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D014665:Vasodilator Agents; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019793:Fluorescein