(Hypertension. 1999;34:563-567.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Role of Nitric Oxide in the Control of Cardiac Oxygen Consumption in B2-Kinin Receptor Knockout Mice
From the Department of Physiology, New York Medical College, Valhalla, NY (K.E.L, C.M.L.C., E.J.M., S.K.L., T.H.H.), and the Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Mich (E.G.S., O.A.C.).
Correspondence to Thomas H. Hintze, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail Thomas Hintze{at}NYMC.eduHintze@NYMC.edu
Abstract—The aim of this study
was to determine whether bradykinin, the
angiotensin-converting enzyme inhibitor
ramiprilat, and the calcium-channel
antagonist amlodipine reduce myocardial oxygen consumption
(M
O2) via a B2-kinin
receptor/nitric oxide–dependent mechanism. Left
ventricular free wall and septum were isolated from normal
and B2-kinin receptor knockout (B2 -/-) mice.
Myocardial tissue oxygen consumption was measured in an airtight
chamber with a Clark-type oxygen electrode. Baseline
MO2 was not significantly different
between normal (239±13 nmol of O2 ·
min-1 · g-1) and B2 -/-
(263±24 nmol of O2 · min-1 ·
g-1) mice. S-nitroso-N-acetyl-penicillamine
(10-7 to 10-4 mol/L) reduced oxygen
consumption in a concentration-dependent manner in both normal
(maximum, 36±3%) and B2 -/- mice (28±3%). This was
also true for the endothelium-dependent vasodilator
substance P (10-10 to 10-7 mol/L; 22±7% in
normal mice and 20±4% in B2 -/- mice). Bradykinin
(10-7 to 10-4 mol/L), ramiprilat
(10-7 to 10-4 mol/L), and amlodipine
(10-7 to 10-5 mol/L) all caused
concentration-dependent decreases in MO2
in normal mice. At the highest concentration, tissue O2
consumption was decreased by 18±3%, 20±5%, and 28±3%,
respectively. The reduction in MO2 to
all 3 drugs was attenuated in the presence of
NG-nitro-L-arginine-methyl ester. However, in
the B2 -/- mice, bradykinin, ramiprilat, and
amlodipine had virtually no effect on
MO2. Therefore, nitric oxide, through a
bradykinin-receptor–dependent mechanism, regulates cardiac oxygen
consumption. This physiological mechanism is absent
in B2 -/- mice and may be evidence of an important
therapeutic mechanism of action of angiotensin-converting
enzyme inhibitors and amlodipine.
Key Words: heart • oxygen • angiotensin-converting enzyme inhibitors • amlodipine
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