Multiple mechanisms for vasodilator effect of magnesium

越来越多的证据表明，镁缺乏不仅会导致高血压，还会加速高血压的并发症，如缺血性心脏病。这些疾病可能与镁的血管效应有关。镁已被证实可直接扩张血管，但可能通过其他机制间接影响血管张力，因此我们研究了镁缺乏和过量对血管内皮细胞和交感神经功能的影响。(1)7周龄SD大鼠以低(3.27 mg/100g)和高(87mN/100g)镁饲料喂养4周。与富镁大鼠相比，缺镁大鼠的血清镁水平极低。低镁大鼠的收缩压为130士5毫米汞柱，富镁大鼠的收缩压为120士士3毫米汞柱(0.05和0.1)。在完整的主动脉环上，钾(K)引起的收缩在两组之间没有差异，但在镁缺乏的…中，去甲肾上腺素(NE)引起的收缩的最大收缩(E&lt；max&gt；)和PD_2降低更多的老鼠。内皮剥脱可使缺镁大鼠的PD_2恢复正常，但不能恢复E&lt；max&Gt；因此，缺镁大鼠的血管反应性受到抑制，这可能是对缺镁引起的血压升高的补偿。这种作用至少部分是通过内皮功能来实现的。(2)在SD大鼠离体肠系膜动脉灌流系统上观察了细胞外镁对血管交感神经活动的影响。交感神经活动以升压反应和血管周围电刺激增加去甲肾上腺素(NE)溢出为指标。当灌流液中的镁浓度从1.2 mM(正常水平)改变到0.3 mM时，电刺激对灌流压和NE溢出的反应增强。另一方面，高浓度(4.8 mM)的镁降低了它的含量。因此，镁抑制血管交感神经活动。最近，包括我们在内的一些研究人员证明血管紧张素II(AngII)增强了外周交感神经活动。然而，增加灌流液的镁浓度，抑制血管紧张素Ⅱ诱导的交感神经系统的增强。由于血管紧张素Ⅱ是在血管系统(如血管内皮细胞)局部产生的，镁可能通过间接机制，如对内皮细胞功能的影响及其直接作用来调节交感神经活动。较少

Accumulating evidence suggests that deficiency of magnesium (Mg) not only cause hypertension but also accelerates its complication such as ischemic heart disease. These illness should be related to vascular effect of Mg. Mg has been demonstrated to directly dilate vasculature but might affect vascular tone indirectly through the other mechanisms so we examined the effect of Mg deficiency and excess on vascular endothelial and sympathetic nervous function.(1) 7 week-old Sprague-Dawley (SD) rats was fed on low (3.27mg/100g) and high (87mn/100g) Mg diet for 4 weeks. Mg-deficient rats showed extremely low level of serum Mg compared with Mg-enriched rats. Systolic blood pressure was 130(〕SY.+-.〔)5 mmHg in Mg-dificient rats and 120(〕SY.+-.〔)3 mmHg in Mg-enriched rats (0.05<P<0.1). In intact aortic ring, Potassium (K)-induced contraction was not different between the two groups but maximal contraction (E_<max>) and pD_2 of norepinephrine (NE)-induced contraction was decreased in Mg-deficient … More rats. Endothelial denudation normalized pD_2 of Mg-deficient rats but no E_<max>. Thus, vascular reactivity is suppressed in Mg-deficient rats, which may compensate for the rise in blood pressure due to Mg-deficiency. This effect may at least party be mediated through endothelial function.(2) We examined the effect of extracellular magnesium on vascular sympathetic nerve activity using the perfusion system of isolated mesenteric artery of SD rats. Sympathetic activity was evaluated as pressor response and increased NE overflow by perivascular electrical stimulation. When Mg concentration in the perfusate was changed from 1.2 mM (normal level) to 0.3 mM, the responses of perfusion pressure and NE overflow by the electrical stimulation was enhanced. On the other hand, high(4.8 mM) Mg decreased it. Thus, Mg inhibits the vascular sympathetic nerve activity. Recently, several investigators including us demonstrated that angiotensin II(ANGII) enhanced the peripheral sympathetic activity. Increased Mg concentration of perfusate, however, suppressed the ANGII-induced enhancement of the sympathetic nervous system. Because ANGII is locally generated in vasculature (for example, endothelial cells), Mg may modify the sympathetic activity through indirect mechanism such as effect on endothelial function as well as its direct action.In summary, Mg modifies vascular tone through not only the direct action on vascular smooth muscle but also the indirect ones via endothelial cells and sympathetic nerve. Less