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原发性高血压患者血小板中早期激动剂诱导的细胞内酸化增加。

Early agonist-induced intracellular acidification is increased in platelets from patients with essential hypertension.

作者信息

Lechi C, Guzzo P, Arosio E, Paluani F, Delva P, Bellavite P, Lechi A

机构信息

Istituti di Clinica Medica e di Chimica Clinica, University of Verona, Italy.

出版信息

Am J Hypertens. 1994 Dec;7(12):1090-6. doi: 10.1093/ajh/7.12.1090.

DOI:10.1093/ajh/7.12.1090
PMID:7702804
Abstract

Enhanced Na+/H+ exchange has been reported to be increased in patients with essential hypertension. However, early variations of intracellular pH, although influenced by the antiport, are only partially dependent on the exchange. In this study, we measured the initial platelet pH response to agonists in a group of untreated subjects with essential hypertension (EH, n = 24) and in a group of age- and sex-matched normotensive control subjects (CS, n = 24). Intracellular pH was measured with the specific fluorescence indicator 2'7'bis(carboxyethyl)-5,6-carboxyfluorescein. Measurements were performed on platelets in the presence or absence of extracellular calcium, in a carbonate-free medium. Intracellular calcium was measured by the Fura 2 method. Mean pH values were slightly higher in the platelets of EH (7.469 +/- 0.017 U) compared with CS (7.423 +/- 0.012 U, P < .05), although there was a substantial overlap. When stimulated with physiologic agonists ADP and thrombin and with the calcium ionophore ionomycin, a biphasic response consisting of early acidification followed by alkalinization was observed, the second phase not being detectable with ADP. The initial acidification was greater in EH, particularly with ADP (EH, -0.046 +/- 0.002 U; CS, -0.036 +/- 0.002 U, P < .001) and with ionomycin (EH, -0.074 +/- 0.007 U; CS, -0.051 +/- 0.005 U, P < .05). This acidification proved in some way calcium dependent, as it was reduced in the absence of extracellular calcium (EGTA) in both EH and CS. After incubation with amiloride a further decrease in intracellular pH, more marked in EH, was observed. Alkalinization induced by thrombin was increased in EH (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

据报道,原发性高血压患者的钠氢交换增强。然而,细胞内pH值的早期变化虽然受反向转运体影响,但只是部分依赖于这种交换。在本研究中,我们测量了一组未经治疗的原发性高血压患者(EH,n = 24)和一组年龄及性别匹配的血压正常对照者(CS,n = 24)的血小板对激动剂的初始pH反应。使用特异性荧光指示剂2'7'-双(羧乙基)-5,6-羧基荧光素测量细胞内pH值。在无细胞外钙的无碳酸盐培养基中,对血小板进行有无细胞外钙存在时的测量。通过Fura 2法测量细胞内钙。与CS组(7.423±0.012 U)相比,EH组血小板的平均pH值略高(7.469±0.017 U,P < 0.05),尽管存在大量重叠。当用生理性激动剂ADP、凝血酶以及钙离子载体离子霉素刺激时,观察到一种双相反应,包括早期酸化随后碱化,第二阶段用ADP无法检测到。EH组的初始酸化更大,特别是对ADP(EH组,-0.046±0.002 U;CS组,-0.036±0.002 U,P < 0.001)和离子霉素(EH组,-0.074±0.007 U;CS组,-0.051±0.005 U,P < 0.05)。这种酸化在某种程度上被证明是钙依赖性的,因为在EH组和CS组中,无细胞外钙(EGTA)时酸化都会降低。用氨氯吡咪孵育后,观察到细胞内pH值进一步降低,在EH组更明显。凝血酶诱导的碱化在EH组增加(P < 0.05)。(摘要截断于250字)

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