(Hypertension. 1997;30:217-221.)
© 1997 American Heart Association, Inc.
Articles |
Angiotensin-(1-7) Induces Bradykinin-Mediated Hypotensive Responses in Anesthetized Rats
From the Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich.
Correspondence to A.G. Scicli, PhD, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 West Grand Blvd, Detroit MI 48202-2689. E-mail agscicli{at}aol.com
Abstract Angiotensin-(1-7) [Ang-(1-7)]
reportedly potentiates hypotensive responses to bradykinin. We studied
whether increases in circulating bradykinin would alter responses to
Ang-(1-7). In rats anesthetized with thiobutabarbital,
bradykinin infusion (5 µg/kg per minute IA) resulted in a rapid
decrease in mean arterial pressure (MAP) of about 20
mm Hg (P<.01, n=9), although MAP slowly increased by
10 mm Hg after 15 minutes. When Ang-(1-7) (20, 80, and 380 nmol
per rat IA) was given during bradykinin infusion, it elicited
hypotension at 80 and 380 nmol (
MAP: -15±2.7 and -21±3.3
mm Hg, respectively; P<.001); this hypotension was not
affected by the angiotensin type 1 antagonist
L-158,809 (200 µg/kg IA), the angiotensin type 2
antagonist PD 123319 (10 mg/kg IA), saralasin, or sarthran
(10 µg/kg per minute). The bradykinin type 2 receptor
antagonist icatibant (30 µg per rat) eliminated the
hypotensive responses to Ang-(1-7), which now increased MAP at all
doses tested (P<.005). Thus in the presence of bradykinin,
Ang-(1-7) induces hypotensive responses that are blocked by icatibant
and unaffected by angiotensin receptor
antagonists. Ang-(1-7) given to saline-infused rats
elicited hypertensive responses at all doses (MAP: 6.4±1.5,
12±1.6, and 16.3±2.7 mm Hg, respectively; P<.01);
these responses were abolished by L-158,809 and sarthran. In rats
pretreated with saralasin, Ang-(1-7) induced hypotension at 80 and 380
nmol (MAP: -7.7±2.3 and -9.5±2.7, respectively;
P<.05), whereas icatibant abolished this response. Thus in
the rat, Ang-(1-7) can decrease blood pressure by a mechanism involving
the bradykinin type 2 receptor and participates with bradykinin in a
vasodepressor pathway that may serve a counterregulatory role,
modulating the vasoconstrictor effects of Ang II.
Key Words: angiotensin-(1-7) • rats • angiotensin • bradykinin • blood pressure
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