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From the Hypertension Center, The Bowman Gray School of Medicine of Wake
Forest University, Winston-Salem, NC.
Correspondence to Carlos M. Ferrario, MD, Hypertension Center, The Bowman Gray School of Medicine of Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157. E-mail cferrari{at}bgsm.edu
Abstract—Blockade of
angiotensin II (Ang II) function during 8 days of oral
therapy with lisinopril (20 mg/kg) and losartan (10
mg/kg) normalized the arterial pressure (112±3/70±3
mm Hg) and raised the plasma concentrations of the vasodilator peptide
angiotensin-(1–7) [Ang-(1–7)] of 21 male spontaneously
hypertensive rats (SHR). Treated animals were then given a 15-minute
infusion of either mouse immunoglobulin G1 or a specific
monoclonal Ang-(1–7) antibody while their blood pressure and heart
rate were recorded continuously in the awake state. The
concentrations of Ang II and Ang-(1–7) in arterial blood
were determined by radioimmunoassay. Infusion of the Ang-(1–7)
antibody caused significant elevations in mean arterial
pressure that were sustained for the duration of the infusion and were
accompanied by transient bradycardia. Although the
hemodynamic effects produced by infusion of the
Ang-(1–7) antibody had no effect on plasma levels of Ang II, they
caused a twofold rise in the plasma concentrations of Ang-(1–7). A
pressor response of similar magnitude and characteristics was obtained
in a separate group of SHR treated with the combination of
lisinopril and losartan for 8 days during an
infusion of [Sar1-Thr8]Ang II. The pressor
response induced by the administration of this competitive,
non–subtype-selective Ang II receptor blocker was not modified by
pretreatment of the rats with an angiotensin type-2
(AT2) receptor blocker (PD123319). Plasma concentrations of
Ang II and Ang-(1–7) were not changed by the administration of
[Sar1-Thr8]Ang II either in the absence or in
the presence of PD123319 pretreatment. These results are the first to
indicate an important contribution of Ang-(1–7) in mediating the
vasodilator effects caused by combined inhibition of
angiotensin-converting enzyme and AT1
receptors. The comparable results obtained by administration of
[Sar1-Thr8]Ang II suggest that the
vasodepressor effects of Ang-(1–7) during the combined treatment is
modulated by a non-AT1/AT2
angiotensin subtype receptor.
© 1998 American Heart Association, Inc.
Scientific Contributions
Vasodepressor Actions of Angiotensin-(1–7) Unmasked During Combined Treatment With Lisinopril and Losartan
Key Words: angiotensin-(1–7) • angiotensin peptides • receptors, angiotensin • blood pressure • losartan • renin-angiotensin system
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