Tepel M, Jankowski J, Ruess C, Steinmetz M, van der Giet M, Zidek W
Universitätsklinik Marienhospital, Medizinische Klinik I, Ruhr-Universität Bochum, Herne, Germany.
Am J Hypertens. 1998 Oct;11(10):1214-21. doi: 10.1016/s0895-7061(98)00127-7.
To evaluate the influence of the sodium/proton exchanger (Na+,H+ exchanger) on the constriction of rat resistance vessels and on the iliac artery, the isometric vasoconstrictions of renal resistance vessels and strips from iliac artery derived from Wistar-Kyoto rats were measured using a vessel myograph. The Na+,H+ exchanger was activated by intracellular acidification using propionic acid. Cytosolic pH (pHi) and cytosolic free sodium concentration ([Na+]i) in vascular smooth muscle cells were measured using the fluorescent dye technique. The activation of the Na+,H+ exchanger increased the [Na+]i by 12.4 +/- 1.3 mmol/L (n = 8). The activation of the Na+,H+ exchanger caused a contractile response of the renal resistance vessels (increase of tension, 1.5 +/- 0.1 x 10(-3) N; n = 13) and of the rat iliac artery (increase of tension, 7.5 +/- 0.8 x 10(-3) N; n = 5). The contractile response after activation of the Na+,H+ exchanger was significantly inhibited in the absence of external sodium or in the presence of amiloride, confirming the involvement of the Na+,H+ exchanger. The contractile response after activation of the Na+,H+ exchanger was significantly reduced in the absence of external calcium, after inhibition of calcium channels by nifedipine, and in the presence of an intracellular calcium antagonist 8-(diethylamino-)-octyl-3,4,5-trimethoxybenzoate (TMB-8), indicating that the activation of the Na+,H+ exchanger consecutively caused transplasma membrane calcium influx. On the other hand, the inhibition of the Na+,Ca2+ exchanger by NiCl2 significantly increased the vasoconstriction of renal resistance vessels after activation of the Na+,H+ exchanger. The activation of the Na+,H+ exchanger produces vasoconstriction by an increased cytosolic sodium concentration, inhibition of the Na+,Ca2+ exchanger, and activation of transplasma membrane calcium influx through potential dependent calcium channels.
为了评估钠/质子交换体（Na⁺，H⁺交换体）对大鼠阻力血管和髂动脉收缩的影响，使用血管肌张力测定仪测量了来自Wistar - Kyoto大鼠的肾阻力血管和髂动脉条带的等长血管收缩情况。通过使用丙酸使细胞内酸化来激活Na⁺，H⁺交换体。使用荧光染料技术测量血管平滑肌细胞中的细胞溶质pH（pHi）和细胞溶质游离钠浓度（[Na⁺]i）。Na⁺，H⁺交换体的激活使[Na⁺]i增加了12.4±1.3 mmol/L（n = 8）。Na⁺，H⁺交换体的激活引起了肾阻力血管的收缩反应（张力增加，1.5±0.1×10⁻³ N；n = 13）以及大鼠髂动脉的收缩反应（张力增加，7.5±0.8×10⁻³ N；n = 5）。在无细胞外钠或存在氨氯地平的情况下，Na⁺，H⁺交换体激活后的收缩反应受到显著抑制，证实了Na⁺，H⁺交换体的参与。在无细胞外钙、用硝苯地平抑制钙通道以及存在细胞内钙拮抗剂8 - （二乙氨基） - 辛基 - 3,4,5 - 三甲氧基苯甲酸酯（TMB - 8）的情况下，Na⁺，H⁺交换体激活后的收缩反应显著降低，表明Na⁺，H⁺交换体的激活继而引起跨质膜钙内流。另一方面，NiCl₂对Na⁺，Ca²⁺交换体的抑制显著增加了Na⁺，H⁺交换体激活后肾阻力血管的血管收缩。Na⁺，H⁺交换体的激活通过增加细胞溶质钠浓度、抑制Na⁺，Ca²⁺交换体以及通过电压依赖性钙通道激活跨质膜钙内流来产生血管收缩。
