Effect of chronic nNOS inhibition on blood pressure, vasoactivity, and arterial wall structure in Wistar rats

被引:18
作者
Cacanyiova, Sona [1 ]
Kristek, Frantisek [1 ]
Gerova, Maria [1 ]
Krenek, Peter [2 ]
Klimas, Jan [2 ]
机构
[1] Slovak Acad Sci, Inst Normal & Pathol Physiol, Ctr Excellence Cardiovasc Res, Sienkiewiczova 1, Bratislava 81371, Slovakia
[2] Comenius Univ, Dept Pharmacol & Toxicol, Fac Pharm, Bratislava, Slovakia
来源
NITRIC OXIDE-BIOLOGY AND CHEMISTRY | 2009年 / 20卷 / 04期
关键词
Neuronal NO synthase; Hypotrophy; Vasomotor activity; NITRIC-OXIDE SYNTHASE; VASCULAR SMOOTH-MUSCLE; LONG-TERM INHIBITION; ENDOTHELIAL-CELLS; MACULA DENSA; L-ARGININE; CARDIOVASCULAR-SYSTEM; 7-NITROINDAZOLE; HYPERTENSION; EXPRESSION;
D O I
10.1016/j.niox.2009.03.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
While the unequivocal pattern of endothelial nitric oxide (NO) synthase (eNOS) inhibition in cardiovascular control has been recognised, the role of NO produced by neuronal NOS (nNOS) remains unclear. The purpose of the present study was to describe the cardiovascular effects of NO production interference by inhibition of nNOS with 7-nitroindazole (7-NI). Wistar rats (10 weeks old) were used: control and experimental rats were administered 7-NI 10 mg/kg b.w./day in drinking water for 6 weeks. Systolic blood pressure (BP) was measured by the tail-cuff plethysmographic method. Isolated thoracic aortas (TAs) were used to study vasomotor activity of the conduit artery in vitro. The BP response of anaesthetised animals was used to follow the cardiovascular-integrated response in vivo. Geometry of the TA was measured after perfusion fixation (120 mm Hg) by light microscopy. Expression of eNOS was measured in the TA by immunoblot analysis. Although 6 weeks of nNOS inhibition did not alter systolic BP, the heart/body weight ratio was decreased. Relaxation of the TA in response to acetylcholine (10(-9)-10(-5) mol/L) was moderately inhibited. However, no difference in the BP hypotensive response after acetylcholine (0.1, 1, 10 mu g) was observed. The contraction of TA in response to noradrenaline (10(-10)-10(-5) mol/L), and the BP pressor response to noradrenaline (0.1, 1 mu g) was attenuated. The inner diameter of the TA was increased, and the wall thickness, wall cross-sectional area, and wall thickness/inner diameter ratio were decreased. The expression of eNOS in the TA was increased. In summary, cardiac and TA wall hypotrophy, underlined by decreased contractile efficiency, were observed. The results suggested that two constitutive forms of NOS (nNOS, eNOS) likely participate in regulation of cardiovascular tone by different mechanisms. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:304 / 310
页数:7
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