Long-Term Administration of D-NAME Induces Hemodynamic and
Structural Changes in the Cardiovascular System
P. BABÁL1, O. PECHÁŇOVÁ2,
I. BERNÁTOVÁ2
1Department of Pathology, University of South
Alabama, Mobile, AL, USA, 1Department of Pathology, Comenius
University and 2Institute of Normal and
Pathological Physiology, Slovak Academy of Sciences,
Bratislava, Slovak Republic
Received July
30, 1999
Accepted September 21, 1999
Summary
NG-nitro-D-arginine-methyl ester (D-NAME) is
considered to be an inactive enantiomer of L-NAME and is
generally used as the negative control for NO synthase
inhibition with L-NAME. With the aim to compare the effects of
4-week L-NAME and D-NAME treatments on hemodynamic and
cardiovascular structural parameters, four groups of male Wistar
rats were investigated: the controls and groups administered 40
and 20 mg/kg/day of L-NAME and 40 mg/kg/day of D-NAME. At the
end of the experiment, myocardial NO synthase activity decreased
by 42, 24 and 25 %; aortic NO synthase activity decreased by 35,
15 and 13 % vs. controls in the L-NAME 40, L-NAME 20 and
D-NAME 40 groups, respectively. The DNA concentrations in the
myocardium and the aorta increased significantly after L-NAME
and D-NAME treatments. The inhibition of NO synthase was
accompanied by a significant elevation in systolic blood
pressure in all three groups. The LVW/BW ratio increased by 27,
14 and 13 % vs. controls in the L-NAME 40, L-NAME 20 and D-NAME
40 groups, respectively. The aortic wall mass, measured as the
crossectional area, increased by 45, 17 and 25 % vs. controls in
the L-NAME 40, L-NAME 20 and D-NAME 40 groups, respectively.
Myocardial fibrosis represented 0.94 % in the controls, but
7.96, 4.70 and 5.25 % in L-NAME 40, L-NAME 20 and D-NAME 40
groups, respectively. It is concluded that D-NAME, although less
affective than L-NAME, inhibits NO synthase activity resulting
in hemodynamic and structural changes in the cardiovascular
system similar to the changes induced by half the dose of
L-NAME. Thus, the consideration of D-NAME as an inactive
enantiomer and its use as the negative control needs to be
reevaluated.
Key
words
Nitric oxide synthase · L-NAME · D-NAME · Hypertension · Myocardial fibrosis ·
Arterial hyperplasia
Reprint
requests
P. Babál, Department of Pathology, Comenius University, Sasinkova 4, 81108 Bratislava,
Slovakia. E-mail: babal@fmed.uniba.sk
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