Foster C D, Honeyman T W, Scheid C R
Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
Am J Physiol. 1992 Jun;262(6 Pt 2):H1657-62. doi: 10.1152/ajpheart.1992.262.6.H1657.
Na(+)-H+ exchange was examined in segments of the superior mesenteric artery from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats using the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Basal pH values were identical in the two strains (SHR = 7.18 +/- 0.02, WKY = 7.15 +/- 0.01) and exposure to 20-50 mM NH4Cl produced comparable changes in pH in both strains (tissues acidified to pH 6.8). The recovery of intracellular pH (pH(i)) from acid loading in bicarbonate-free buffer was dependent on extracellular Na+, inhibited by dimethyl amiloride, and thus was presumably mediated by Na(+)-H+ exchange. Exchange activity was markedly increased in SHR (0.308 vs. 0.182 pH U/min), and the increased activity could not be explained by differences in intracellular buffer capacity or in the Na+ affinity of the transporter. The rate of Na(+)-H+ exchange was more steeply dependent on pH(i) in SHR vessels Hill coefficient = 6.6 in SHR vs. 4.1 in WKY), suggesting an alteration in the transport protein. Young SHR (4-6 wk) exhibited kinetic characteristics resembling those of 12- to 14-wk-old WKY rats. Exposure to the Ca2+ ionophore bromo-A23187 significantly increased the Hill coefficient of WKY arteries but had no effect on vessels from SHR. Exposure of vessels from either strain to the phorbol ester phorbol 12-myristate 13 acetate (PMA) had no effect on Na(+)-H+ exchange.
使用pH敏感染料2',7'-双(2-羧乙基)-5(6)-羧基荧光素(BCECF),对自发性高血压大鼠(SHR)和Wistar-Kyoto大鼠(WKY)肠系膜上动脉节段的Na(+)-H+交换进行了检测。两种品系的基础pH值相同(SHR = 7.18±0.02,WKY = 7.15±0.01),暴露于20 - 50 mM氯化铵会使两种品系的pH产生类似变化(组织酸化至pH 6.8)。在无碳酸氢盐缓冲液中酸负荷后细胞内pH(pH(i))的恢复依赖于细胞外Na+,受二甲基氨氯吡脒抑制,因此推测是由Na(+)-H+交换介导的。SHR的交换活性显著增加(0.308对0.182 pH单位/分钟),且活性增加无法用细胞内缓冲能力或转运体对Na+的亲和力差异来解释。SHR血管中Na(+)-H+交换速率对pH(i)的依赖性更强(SHR的希尔系数 = 6.6,WKY为4.1),表明转运蛋白发生了改变。年轻的SHR(4 - 6周龄)表现出与12至14周龄WKY大鼠相似的动力学特征。暴露于Ca2+离子载体溴-A23187可显著增加WKY动脉的希尔系数,但对SHR的血管无影响。两种品系的血管暴露于佛波酯佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)对Na(+)-H+交换均无影响。