Physiol. Res. 49: 47-54, 2000

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


© 2000 by the Institute of Physiology, Czech Academy of Sciences