Yanagisawa Hiroyuki, Sato Masamichi, Nodera Makoto, Wada Osamu
Department of Hygiene & Preventive Medicine, Faculty of Medicine, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-Gun, Saitama, Japan.
J Hypertens. 2004 Mar;22(3):543-50. doi: 10.1097/00004872-200403000-00017.
The present study was designed to examine whether or not excessive Zn intake affects systemic blood pressure (BP) levels in a normotensive state.
Systolic BP (SBP) and mean arterial pressure (MAP) before and after administration of the nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME) or the exogenous superoxide scavenger, tempol and the activity of the endogenous superoxide scavenger, Cu/Zn-superoxide dismutase (SOD) and levels of endothelial type (e)NOS mRNA and protein in the thoracic aorta were analyzed in male Sprague-Dawley rats fed a standard diet containing 0.005% Zn or a high Zn diet containing 0.5% Zn for 8 weeks.
SBP and MAP levels observed at the end of dietary conditioning were significantly elevated in rats fed a high Zn diet relative to rats fed a standard diet. Administration of L-NAME caused an increase in MAP levels in rats fed a standard and a high Zn diet, demonstrating the involvement of the vasodilator, nitric oxide (NO) in the regulation of systemic BP in the two groups of rats. However, the expression of eNOS mRNA and protein in the thoracic aorta was not significantly different between rats fed a standard and a high Zn diet. On the other hand, administration of tempol led to a decrease in MAP levels in rats fed a standard and a high Zn diet, indicating the participation of the oxygen free radical, superoxide in the modification of systemic BP in the two groups of rats. As reported recently, the mechanism involved is due likely to a decrease in the action of the vasodilator, NO through the formation of peroxynitrite based on the non-enzymatic reaction of superoxide and NO. In addition, tempol treatment dramatically restored MAP levels in rats fed a high Zn diet to levels comparable with those observed in rats fed a standard diet, indicating that an elevation in systemic BP levels seen in rats fed a high Zn versus a standard diet is presumably brought by a reduction in the action of the vasodilator, NO resulting from an increase in the action of superoxide. The activity of Cu/Zn-SOD in the thoracic aorta was significantly reduced in rats fed a high Zn diet relative to rats fed a standard diet, appearing to at least in part, play a role in an increase in the action of superoxide in the vessel wall of rats fed a high Zn diet.
Excessive Zn intake may be a factor to elevate systemic BP levels in a normotensive state presumably through the oxidative stress caused by superoxide.
本研究旨在探讨过量锌摄入是否会影响正常血压状态下的全身血压（BP）水平。
在雄性Sprague-Dawley大鼠中，分析给予一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸甲酯（L-NAME）或外源性超氧化物清除剂tempol前后的收缩压（SBP）和平均动脉压（MAP），以及给予含0.005%锌的标准饮食或含0.5%锌的高锌饮食8周后胸主动脉中内源性超氧化物清除剂铜/锌超氧化物歧化酶（SOD）的活性、内皮型（e）NOS mRNA和蛋白水平。
与喂食标准饮食的大鼠相比，喂食高锌饮食的大鼠在饮食调节结束时观察到的SBP和MAP水平显著升高。给予L-NAME导致喂食标准饮食和高锌饮食的大鼠MAP水平升高，表明血管舒张剂一氧化氮（NO）参与了两组大鼠全身血压的调节。然而，喂食标准饮食和高锌饮食的大鼠胸主动脉中eNOS mRNA和蛋白的表达没有显著差异。另一方面，给予tempol导致喂食标准饮食和高锌饮食的大鼠MAP水平降低，表明氧自由基超氧化物参与了两组大鼠全身血压的调节。如最近报道的，其涉及的机制可能是由于超氧化物和NO的非酶反应形成过氧亚硝酸盐，导致血管舒张剂NO的作用降低。此外，tempol处理显著将喂食高锌饮食的大鼠的MAP水平恢复到与喂食标准饮食的大鼠相当的水平，表明喂食高锌饮食与标准饮食的大鼠相比，全身血压水平升高可能是由于超氧化物作用增加导致血管舒张剂NO的作用降低所致。与喂食标准饮食的大鼠相比，喂食高锌饮食的大鼠胸主动脉中铜/锌-SOD的活性显著降低，这似乎至少在一定程度上导致了喂食高锌饮食的大鼠血管壁中超氧化物作用的增加。
过量锌摄入可能是在正常血压状态下升高全身血压水平的一个因素，可能是通过超氧化物引起的氧化应激。
