Kido Makiko, Ando Katsuyuki, Onozato Maristela L, Tojo Akihiro, Yoshikawa Masahiro, Ogita Teruhiko, Fujita Toshiro
Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan.
Hypertension. 2008 Feb;51(2):225-31. doi: 10.1161/HYPERTENSIONAHA.107.098251. Epub 2007 Dec 24.
Hypertensive cardiovascular damage is accelerated by salt loading but counteracted by dietary potassium supplementation. We suggested recently that antioxidant actions of potassium contribute to protection against salt-induced cardiac dysfunction. Therefore, we examined whether potassium supplementation ameliorated cuff-induced vascular injury in salt-sensitive hypertension via suppression of oxidative stress. Four-week-old Dahl salt-sensitive rats were fed a normal-salt (0.3% NaCl), high-salt (8% NaCl), or high-salt plus high-potassium (8% KCl) diet for 5 weeks, and some of the rats fed a high-salt diet were also given antioxidants. One week after the start of the treatments, a silicone cuff was implanted around the femoral artery. Examination revealed increased cuff-induced neointimal proliferation with adventitial macrophage infiltration in arteries from salt-loaded Dahl salt-sensitive rats compared with that in arteries from non-salt-loaded animals (intima/media ratio: 0.471+/-0.070 versus 0.302+/-0.037; P<0.05), associated with regional superoxide overproduction and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and mRNA overexpression. On the other hand, simultaneous potassium supplementation attenuated salt-induced neointimal hyperplasia (intima/media ratio: 0.205+/-0.012; P<0.001), adventitial macrophage infiltration, superoxide overproduction, and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and overexpression. Antioxidants, which decrease vascular oxidative stress, also reduced neointima formation induced by salt excess. In conclusion, high-potassium diets seems to have a protective effect against the development of vascular damage induced by salt loading mediated, at least in part, through suppression of the production of reactive oxygen species probably generated by reduced nicotinamide-adenine dinucleotide phosphate oxidase.
盐负荷会加速高血压性心血管损伤，但膳食补充钾可起到抵消作用。我们最近提出，钾的抗氧化作用有助于预防盐诱导的心脏功能障碍。因此，我们研究了补充钾是否通过抑制氧化应激来改善盐敏感性高血压中袖带诱导的血管损伤。给四周龄的 Dahl 盐敏感性大鼠喂食正常盐（0.3% NaCl）、高盐（8% NaCl）或高盐加高钾（8% KCl）饮食 5 周，并且给一些喂食高盐饮食的大鼠同时给予抗氧化剂。在治疗开始一周后，在股动脉周围植入硅胶袖带。检查发现，与未进行盐负荷的动物相比，盐负荷的 Dahl 盐敏感性大鼠动脉中袖带诱导的内膜增生增加，伴有外膜巨噬细胞浸润（内膜/中膜比值：0.471±0.070 对 0.302±0.037；P<0.05），同时伴有局部超氧化物过量产生以及烟酰胺腺嘌呤二核苷酸磷酸氧化酶激活和 mRNA 过表达降低。另一方面，同时补充钾可减轻盐诱导的内膜增生（内膜/中膜比值：0.205±0.012；P<0.001）、外膜巨噬细胞浸润、超氧化物过量产生以及烟酰胺腺嘌呤二核苷酸磷酸氧化酶激活和过表达降低。可降低血管氧化应激的抗氧化剂也减少了盐过量诱导的新内膜形成。总之，高钾饮食似乎对盐负荷诱导的血管损伤发展具有保护作用，这至少部分是通过抑制可能由烟酰胺腺嘌呤二核苷酸磷酸氧化酶产生减少而生成的活性氧的产生来介导的。
