■缺乏钾(K+)的饮食,典型的现代加工食品,增加血压(BP)和NaCl敏感性。肾远曲小管中的K依赖性信号通路,创造了K+开关,涉及到细胞外K感应与噻嗪敏感的NaCl协同转运蛋白(NCC)和NaCl保留的激活有关,但因果关系尚未确定。
■为了检验这一假设,血浆K+(PK+)的生理变化通过开关途径转化为BP,使用遗传方法来激活下游开关激酶,SPAK(SPS1相关脯氨酸/富含丙氨酸激酶),在远曲小管内。在饮食K变化引起的4天PK滴定(3.8-5.1mmol)中,将CA-SPAK(组成型活性的SPS1相关的脯氨酸/富含丙氨酸的激酶小鼠)与对照小鼠进行了比较。使用无线电遥测术监测动脉血压,和肾功能测量,NCC丰度,磷酸化,并进行了活动。
■由于对照组小鼠的PK降低,血压逐渐增加,对饮食中的NaCl和氢氯噻嗪变得敏感,与NCC磷酸化和尿钠潴留增加一致。相比之下,CA-SPAK小鼠的血压升高,耐PK+滴定,对所有PK+水平的氢氯噻嗪和盐敏感,伴随持续和升高的尿钠潴留和NCC磷酸化和活性。因此,遗传锁定开关驱动NaCl敏感性,并防止BP对钾的反应。
■低K+,在现代超加工饮食中很常见,按下K+开关通路打开NCC活动,增加钠潴留,BP,盐的敏感性。
UNASSIGNED: Potassium (K+)-deficient diets, typical of modern processed foods, increase blood pressure (BP) and NaCl sensitivity. A K+-dependent signaling pathway in the kidney distal convoluted tubule, coined the K+ switch, that couples extracellular K+ sensing to activation of the thiazide-sensitive NaCl cotransporter (NCC) and NaCl retention has been implicated, but causality has not been established.
UNASSIGNED: To test the hypothesis that small, physiological changes in plasma K+ (PK+) are translated to BP through the switch pathway, a genetic approach was used to activate the downstream switch kinase, SPAK (SPS1-related proline/alanine-rich kinase), within the distal convoluted tubule. The CA-SPAK (constitutively active SPS1-related proline/alanine-rich kinase mice) were compared with control mice over a 4-day PK+ titration (3.8-5.1 mmol) induced by changes in dietary K+. Arterial BP was monitored using radiotelemetry, and renal function measurements, NCC abundance, phosphorylation, and activity were made.
UNASSIGNED: As PK+ decreased in control mice, BP progressively increased and became sensitive to dietary NaCl and hydrochlorothiazide, coincident with increased NCC phosphorylation and urinary sodium retention. By contrast, BP in CA-SPAK mice was elevated, resistant to the PK+ titration, and sensitive to hydrochlorothiazide and salt at all PK+ levels, concomitant with sustained and elevated urinary sodium retention and NCC phosphorylation and activity. Thus, genetically locking the switch on drives NaCl sensitivity and prevents the response of BP to potassium.
UNASSIGNED: Low K+, common in modern ultraprocessed diets, presses the K+-switch pathway to turn on NCC activity, increasing sodium retention, BP, and salt sensitivity.