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(Hypertension. 1999;34:943-949.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Role of Angiotensin and Oxidative Stress in Essential Hypertension
From the Department of Physiology and Biophysics, Mayo School of Medicine and Division of Hypertension, Mayo Clinic (J.C.R.) Rochester, Minn; and the Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center (J.F.R.), Jackson, Miss.
Correspondence to J. Carlos Romero, MD, Department of Physiology, Mayo Clinic, Rochester, MN 55905.
Abstract—In this review, we
examine the possibility that small increments in
angiotensin II are responsible for an increase in blood
pressure and maintenance of hypertension through the
stimulation of oxidative stress. A low dose of angiotensin
II (2 to 10 ng · kg-1 · min-1,
which does not elicit an immediate pressor response), when given for 7
to 30 days by continuous intravenous infusion, can increase
mean arterial pressure by 30 to 40 mm Hg. This slow
pressor response to angiotensin is accompanied by the
stimulation of oxidative stress, as measured by a significant increase
in levels of 8-iso-prostaglandin F2
(F2-isoprostane). Superoxide radicals and nitric oxide can
combine chemically to form peroxynitrite, which can then oxidize
arachidonic acid to form
F2-isoprostanes. F2-isoprostanes exert
potent vasoconstrictor and antinatriuretic effects.
Furthermore, angiotensin II can stimulate endothelin
production, which also has been shown to stimulate oxidative
stress. In this way, a reduction in the concentration of nitric oxide
(which is quenched by superoxide) along with the formation of
F2-isoprostanes and endothelin could potentiate the
vasoconstrictor effects of angiotensin II. We hypothesize
that these mechanisms, which underlie the development of the slow
pressor response to angiotensin II, also participate in the
production of hypertension when circulating
angiotensin II levels appear normal, as occurs in many
cases of essential and renovascular hypertension.
Key Words: isoprostane • endothelin • oxidative stress • hypertension, essential • angiotensin II
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