Mechanism of structural remodelling of the rat aorta during long-term NG-nitro-L-arginine methyl ester treatment

被引:42
作者
Bernátová, I [1 ]
Pechánová, O [1 ]
Kristek, F [1 ]
机构
[1] Slovak Acad Sci, Inst Normal & Pathol Physiol, Dept Cardiovasc Physiol, Bratislava 81371, Slovakia
关键词
nitric oxide; N-G-nitro-L-arginine methyl ester; blood pressure; cAMP; aorta;
D O I
10.1254/jjp.81.99
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of the present study was to determine whether decreased nitric oxide (NO) synthase production or rather N-G-nitro-L-arginine methyl ester (L-NAME)-induced hypertension was responsible for metabolic and structural remodelling of the rat aorta during four-week L-NAME treatment. Three groups of male Wistar rats were investigated: control, treated with 20 mg/kg per day L-NAME (L-NAME(20)), and treated with 40 mg/kg per day L-NAME (L-NAME(40)). Systolic blood pressure significantly increased in L-NAME(20) to 146% and in L-NAME(40) to 149% of the control value. NO synthase activity in the aorta significantly decreased in L-NAME(20) and L-NAME(40) to 86% and 65% of the control values, respectively. Proteosynthesis was significantly elevated in both L-NAME groups, while nuclear DNA concentration was significantly elevated only in the L-NAME(40) group. Cyclic GMP concentration significantly decreased in L-NAME(20) to 73% and in L-NAME(40) to 46% of the control. Cyclic AMP concentration significantly increased in L-NAME(20) and L-NAME(40) to 128% and 145% of the control value, respectively. The diameter and wall thickness-to-diameter ratio were significantly elevated only in the L-NAME(40) group. We conclude that remodelling of the aorta in L-NAME-treated rats was rather associated with NO deficiency than L-NAME-induced hypertension.
引用
收藏
页码:99 / 106
页数:8
相关论文
共 38 条
[1]   DETERMINANTS OF AORTIC CYCLIC GUANOSINE-MONOPHOSPHATE IN HYPERTENSION INDUCED BY CHRONIC INHIBITION OF NITRIC-OXIDE SYNTHASE [J].
ARNAL, JF ;
WARIN, L ;
MICHEL, JB .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (02) :647-652
[2]  
Babal P, 1997, HISTOL HISTOPATHOL, V12, P623
[3]  
Bernatova I, 1996, PHYSIOL RES, V45, P311
[4]   ISOLATION OF NITRIC-OXIDE SYNTHETASE, A CALMODULIN-REQUIRING ENZYME [J].
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (02) :682-685
[5]   Maintenance of vascular integrity: Role of nitric oxide and other bradykinin mediators [J].
Cosentino, E ;
Luscher, TF .
EUROPEAN HEART JOURNAL, 1995, 16 :4-12
[6]  
DAVIDSON NJ, 1976, BIOCH NUKLEINOVYCH K, P79
[7]   NITRIC-OXIDE INDUCES OXIDATIVE DAMAGE IN ADDITION TO DEAMINATION IN MACROPHAGE DNA [J].
DEROJASWALKER, T ;
TAMIR, S ;
JI, H ;
WISHNOK, JS ;
TANNENBAUM, SR .
CHEMICAL RESEARCH IN TOXICOLOGY, 1995, 8 (03) :473-477
[8]   Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo [J].
Devlin, AM ;
Brosnan, MJ ;
Graham, D ;
Morton, JJ ;
McPhaden, AR ;
McIntyre, M ;
Hamilton, CA ;
Reid, JL ;
Dominiczak, AF .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1998, 274 (01) :H52-H59
[9]  
GARG U, 1993, EUR J PHARMACOL, V273, P243
[10]   NITRIC OXIDE-GENERATING VASODILATORS AND 8-BROMO-CYCLIC GUANOSINE-MONOPHOSPHATE INHIBIT MITOGENESIS AND PROLIFERATION OF CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS [J].
GARG, UC ;
HASSID, A .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (05) :1774-1777