From the Department of Physiology, New York Medical College, Valhalla,
NY.
Correspondence to Thomas H. Hintze, PhD, Professor, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail Thomas-Hintze{at}NYMC.edu
Background—Recent studies suggest
that amlodipine may reduce mortality in patients with heart failure,
especially those with dilated cardiomyopathy. In
general, drugs that release NO, such as organic nitrates and ACE
inhibitors, have been shown to be of substantial benefit in
the treatment of heart failure.
Methods and Results—We hypothesized that a portion of the
beneficial actions of amlodipine may involve the release or action of
NO. Coronary microvessels were isolated from the heart of
normal dogs and incubated with increasing doses of the calcium channel
blockers nifedipine, diltiazem, and amlodipine or the ACE
inhibitors enalaprilat and ramiprilat. Neither
nifedipine nor diltiazem increased nitrite
production at any dose studied. In marked contrast, amlodipine
caused a dose-dependent increase in nitrite production from
74±5 to 130±8 pmol/mg (by 85±21%,10-5 mol/L,
P<.05) that was similar in magnitude to that of either
of the ACE inhibitors. Amlodipine also increased nitrite
production in large coronary arteries and in aorta.
N
Conclusions—Thus, unlike nifedipine and diltiazem,
amlodipine releases NO from blood vessels.
© 1998 American Heart Association, Inc.
Basic Science Reports
Amlodipine Releases Nitric Oxide From Canine Coronary Microvessels
An Unexpected Mechanism of Action of a Calcium Channel–Blocking Agent
-Nitro-L-arginine methyl
ester, HOE-140, and dichloroisocoumarin essentially abolished the
increase in nitrite production, indicating that (1) nitrite
production reflected NO formation, (2) nitrite
production was dependent on stimulation of the
kinin2 receptor, and (3) nitrite production is most
likely secondary to the formation of local kinins.
Key Words: nifedipine • bradykinin • calcium channels • endothelium-derived factors
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