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WKY和SHR血管平滑肌细胞中Na+/H+交换的动力学:佛波酯的作用

Kinetics of Na+/H+ exchange in vascular smooth muscle cells from WKY and SHR: effects of phorbol ester.

作者信息

Hoffmann G, Ko Y, Sachinidis A, Göbel B O, Vetter H, Rosskopf D, Siffert W, Düsing R

机构信息

Medizinische Universitäts-Poliklinik, Bonn, Germany.

出版信息

Am J Physiol. 1995 Jan;268(1 Pt 1):C14-20. doi: 10.1152/ajpcell.1995.268.1.C14.

DOI:10.1152/ajpcell.1995.268.1.C14
PMID:7840142
Abstract

The kinetic properties of Na+/H+ exchange were investigated in vascular smooth muscle cells (VSMC) in culture from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Antiport activity was measured in 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein-loaded cells after nigericin-induced cytosolic acidification. Studies were performed without (control) and with pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA; 200 nM). Na+/H+ exchange markedly differed between the two strains with lower Hill coefficients [1.56 +/- 0.17 (SE) vs. 2.62 +/- 0.36] and higher maximal activity (Vmax) values (55.85 +/- 5.24 vs. 31.11 +/- 2.38 mmol H+.l-1.min-1) in SHR compared with WKY cell lines. PMA markedly altered the antiport kinetics in WKY VSMC with a decrease in the Hill coefficient (1.75 +/- 0.14) without affecting Vmax (31.88 +/- 1.55 mmol H+.l-1.min-1). In VSMC from SHR, PMA had no effect on the kinetic variables investigated. Thus two kinetic abnormalities are present with respect to Na+/H+ antiport activity in VSMC from SHR compared with WKY, i.e., increased Vmax and decreased Hill coefficient. The observation that PMA does not affect the kinetics of the Na+/H+ antiport in VSMC from SHR suggests a marked degree of antiporter prestimulation in this animal model of genetic hypertension.

摘要

研究了正常血压的Wistar-Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)培养的血管平滑肌细胞(VSMC)中Na+/H+交换的动力学特性。在用尼日利亚菌素诱导胞质酸化后,测量了负载2',7'-双(羧乙基)-5(6)-羧基荧光素的细胞中的反向转运活性。研究在未预处理(对照)和用佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA;200 nM)预处理细胞的情况下进行。两种品系之间的Na+/H+交换存在显著差异,与WKY细胞系相比,SHR的希尔系数较低[1.56±0.17(SE)对2.62±0.36],最大活性(Vmax)值较高(55.85±5.24对31.11±2.38 mmol H+.l-1.min-1)。PMA显著改变了WKY VSMC中的反向转运动力学,希尔系数降低(1.75±0.14),而不影响Vmax(31.88±1.55 mmol H+.l-1.min-1)。在SHR的VSMC中,PMA对所研究的动力学变量没有影响。因此,与WKY相比,SHR的VSMC中Na+/H+反向转运活性存在两种动力学异常,即Vmax增加和希尔系数降低。PMA不影响SHR的VSMC中Na+/H+反向转运动力学的观察结果表明,在这种遗传性高血压动物模型中,反向转运体存在明显程度的预刺激。

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