Hernández Noelina, De Sanctis Juan B, Losada Mercedes, Torres Sonia H, Sosa Amparo, Rivas Miriam
Instituto de Medicina Experimental, Sección de Adaptación Muscular, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.
Invest Clin. 2011 Sep;52(3):239-51.
Systemic diseases affect skeletal muscle, and inflammation and oxidative stress are some of the involved mechanisms. There is scarce information about the effects of essential hypertension on skeletal muscle. The soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and nitrate in micromol/mg-protein; endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor alpha (TNF-alpha) in ng/mg-protein were determined. Compared with controls, the SHR showed increased levels of nitrotyrosine (soleus 24.4 +/- 5.0 vs. 3.3 +/- 0.3, p<0.001; EDL 20.2 +/- 4.3 vs. 4.5 +/- 0.4, p<0.0037), iNOS (soleus 26.6 +/- 3.7 vs. 8.3 +/- 0.9; EDL 21.3 +/- 3.7 vs. 11.0 +/- 0.8, both p<0.0001) and TNF-alpha (soleus 2.2 +/- 0.5 vs. 0.6 +/- 0.1, p<0.05; EDL 1.9 +/- 0.2 vs. 0.6 +/- 0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 +/- 1.4 vs. 30.3 +/- 1.2, p<0.00001); of nNOS (soleus 16.8 +/- 1.4 vs. 20.7 +/- 1.8, p< 0.05; EDL 13.6 +/- 1.3 vs. 21.9 +/- 1.8, p<.005) and nitrite in EDL (5.8 +/- 0.3 vs. 7.1 +/- 0.5, p<0.026).There was a positive correlation between TNF-alpha vs. nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739; p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707; p<0.01), a tendency between TNF-alpha and iNOS (EDL: r=0.736; p<0.059); and a negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816; p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was found evidenced by the increase in TNF-alpha, nitrotyrosine and iNOS. The decreased levels of constitutive synthases, together with the higher level of iNOS, are indicative of endothelial dysfunction.
全身性疾病会影响骨骼肌,炎症和氧化应激是其中一些相关机制。关于原发性高血压对骨骼肌的影响,目前信息匮乏。本研究将自发性高血压大鼠(SHR)的比目鱼肌和趾长伸肌(EDL)与对照Wistar Kyoto(WKY)大鼠进行了比较。测定了每毫克蛋白质中亚硝酸盐和硝酸盐的含量(微摩尔);以及每毫克蛋白质中内皮型(eNOS)、神经元型(nNOS)和诱导型(iNOS)一氧化氮合酶、硝基酪氨酸和肿瘤坏死因子α(TNF-α)的含量(纳克)。与对照组相比,SHR的硝基酪氨酸水平升高(比目鱼肌:24.4±5.0 vs. 3.3±0.3,p<0.001;EDL:20.2±4.3 vs. 4.5±0.4,p<0.0037)、iNOS水平升高(比目鱼肌:26.6±3.7 vs. 8.3±0.9;EDL:21.3±3.7 vs. 11.0±0.8,两者p<0.0001)以及TNF-α水平升高(比目鱼肌:2.2±0.5 vs. 0.6±0.1,p<0.05;EDL:1.9±0.2 vs. 0.6±0.1,p<0.02)。比目鱼肌中eNOS水平降低(20.6±1.4 vs. 30.3±1.2,p<0.00001);nNOS水平降低(比目鱼肌:16.8±1.4 vs. 20.7±1.8,p<0.05;EDL:13.6±1.3 vs. 21.9±1.8,p<0.005),EDL中亚硝酸盐水平降低(5.8±0.3 vs. 7.1±0.5,p<0.026)。比目鱼肌中TNF-α与硝基酪氨酸之间呈正相关(r=0.798;p<0.031),EDL中有此趋势(r=0.739;p=0.059);iNOS与硝基酪氨酸之间呈正相关(比目鱼肌:r=0.908;p<0.0001;EDL:r=0.707;p<0.01),TNF-α与iNOS之间有此趋势(EDL:r=0.736;p<0.059);比目鱼肌中eNOS与硝基酪氨酸之间呈负相关(r=-0.816;p<0.0012)。总之,在SHR的骨骼肌中发现了炎症过程,表现为TNF-α、硝基酪氨酸和iNOS升高。组成型合酶水平降低,以及iNOS水平升高,表明存在内皮功能障碍。