Kristek F, Cacanyiova S, Gerova M
Institute of Normal and Pathological Physiology and Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
J Physiol Pharmacol. 2009 Jun;60(2):21-7.
We demonstrate the effect of long-term nNOS inhibition with 7-nitroindazole (7NI) on the heart and conduit arteries. Ten weeks old Wistar rats were used: two groups of controls and rats receiving 7-NI (10 mg/kg b.w./day) for 6 weeks in drinking water. Blood pressure (BP) was measured by the plethysmographic method. In first group mesenteric, carotid and coronary arteries were excised after perfusion fixation (120 mmHg) for morphological study, in second group mesenteric artery was taken for functional investigation. 7NI did not affect BP, heart/body weight was decreased. In all arteries inner diameter (ID) did not changed, wall thickness (WT) (intima+media), cross sectional area (CSA) (intima+media), and WT/ID decreased. In carotid artery volume density (VD) (percentual proportion) of intima and media did not change; VD and CSAs of endothelial and smooth muscle cells decreased, CSAs of extracellular matrix in intima and media did not change. No difference was found in relaxation of mesenteric artery to acetylcholine (10(-9)-10(-5) mol/L). Contraction induced by transmural nerve stimulation (8 Hz) augmented and contraction to exogennous noradrenaline (10(-9)-10(-5) mol/L) attenuated. Long-term 7NI administration evoked pressure independent cardiac hypotrophy and due to decrease of endothelial and smooth muscle cell mass arterial wall hypotrophy associated with decreased contractile efficiency.
我们展示了用7-硝基吲唑(7NI)长期抑制神经元型一氧化氮合酶(nNOS)对心脏和传导动脉的影响。使用10周龄的Wistar大鼠:两组为对照组,另一组大鼠在饮用水中接受7-NI(10毫克/千克体重/天)处理6周。通过体积描记法测量血压(BP)。第一组在灌注固定(120毫米汞柱)后切除肠系膜、颈动脉和冠状动脉用于形态学研究,第二组取肠系膜动脉进行功能研究。7NI不影响血压,但心脏/体重降低。在所有动脉中,内径(ID)未改变,壁厚(WT)(内膜+中膜)、横截面积(CSA)(内膜+中膜)以及WT/ID降低。在颈动脉中,内膜和中膜的体积密度(VD)(百分比比例)未改变;内皮细胞和平滑肌细胞的VD和CSA降低,内膜和中膜细胞外基质的CSA未改变。肠系膜动脉对乙酰胆碱(10^(-9)-10^(-5)摩尔/升)的舒张反应未发现差异。经壁神经刺激(8赫兹)诱导的收缩增强,对外源性去甲肾上腺素(10^(-9)-10^(-5)摩尔/升)的收缩减弱。长期给予7NI引起压力无关性心脏肥大,并且由于内皮细胞和平滑肌细胞数量减少导致动脉壁肥大,同时收缩效率降低。