Marvar Paul J, Nurkiewicz Timothy R, Boegehold Matthew A
Department of Physiology and Pharmacology, and Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, WV 265056-9229, USA.
J Vasc Res. 2005 May-Jun;42(3):226-36. doi: 10.1159/000085461. Epub 2005 Apr 25.
We previously reported that in skeletal muscle arterioles of rats fed a very high salt (HS; 7%) diet, the bioavailability of endothelium-derived nitric oxide (NO) is reduced through scavenging by reactive oxygen species. Because arteriolar NO can play an important role in local blood flow control, we investigated whether arteriolar responses to increased tissue metabolism become compromised in skeletal muscle of salt-fed rats. Consumption of a HS (4%) diet for 4 weeks had no effect on arteriolar diameters, volume flow or shear stress in resting spinotrapezius muscle. Arteriolar responses to a modest elevation in metabolic demand (0.5 Hz contraction) were not different from those in rats fed a normal diet, but diameter responses to a greater elevation in metabolic demand (4 Hz contraction) were significantly less in HS rats than in rats fed a normal diet. In both groups, the NO synthase inhibitor N(G)-monomethyl-L-arginine reduced resting arteriolar diameters and flow by a similar amount and had little or no effect on arteriolar diameter or flow responses to muscle contraction. Arterioles in HS rats exhibited an increase in overall oxidant activity (tetranitroblue tetrazolium reduction) but not in superoxide activity (dihydroethidine oxidation). Reactive oxygen species scavengers (2,2,6,6-tetramethylpiperidine-N-oxyl and catalase) did not normalize the reduced arteriolar responses to muscle contraction in HS rats. These findings suggest that increased oxidant activity in the arteriolar network of salt-fed rats is not due to accumulation of superoxide anion and that neither this oxidant activity nor reduced NO availability can account for the blunted active arteriolar dilation in rats fed a 4% salt diet.
我们之前报道过，在喂食高盐（HS；7%）饮食的大鼠骨骼肌小动脉中，内皮源性一氧化氮（NO）的生物利用度因活性氧的清除作用而降低。由于小动脉NO在局部血流控制中可发挥重要作用，我们研究了在喂食高盐的大鼠骨骼肌中，小动脉对组织代谢增加的反应是否受损。喂食4周HS（4%）饮食对静息斜方肌的小动脉直径、容积流量或剪切应力没有影响。小动脉对代谢需求适度升高（0.5 Hz收缩）的反应与喂食正常饮食的大鼠无异，但在HS大鼠中，小动脉对代谢需求更大升高（4 Hz收缩）的直径反应明显小于喂食正常饮食的大鼠。在两组中，NO合酶抑制剂N(G)-单甲基-L-精氨酸使静息小动脉直径和流量减少的幅度相似，对小动脉直径或对肌肉收缩的流量反应几乎没有影响。HS大鼠的小动脉总体氧化活性（四氮唑蓝还原）增加，但超氧化物活性（二氢乙锭氧化）未增加。活性氧清除剂（2,2,6,6-四甲基哌啶-N-氧化物和过氧化氢酶）未能使HS大鼠小动脉对肌肉收缩的反应减弱恢复正常。这些发现表明，喂食高盐大鼠小动脉网络中氧化活性的增加并非由于超氧阴离子的积累，并且这种氧化活性和NO可用性的降低都不能解释喂食4%盐饮食的大鼠中主动小动脉扩张减弱的现象。
