Soszynski P, Ensign A, Graves S W, Hollenberg N K
Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Am J Hypertens. 1997 Dec;10(12 Pt 1):1342-8. doi: 10.1016/s0895-7061(97)00266-5.
Although multiple lines of evidence have suggested that a circulating endogenous digitalis-like factor (DLF) might contribute to the pathogenesis of sodium-sensitive hypertension, the subject remains controversial. This study was designed to compare the influence of potassium on vascular responses to an endogenous DLF isolated from peritoneal dialysate (PD) in volume-expanded patients with other sodium pump inhibitors, such as ouabain and bufalin, and the influence of serotonin as an index of specificity. An increase in bath potassium (K+) concentration from 2.7 to 10 mmol/L relaxed bovine facial artery precontracted with serotonin, but induced a secondary paradoxical contractile response in vascular-smooth muscle (VSM) precontracted with ouabain, bufalin, or the endogenous DLF from PD. There was a strong correlation between the primary contraction induced by each sodium pump inhibitor, and the magnitude of the paradoxical secondary contractile response. The increase in potassium concentration did not influence ouabain binding in the 20 min required for the experimental protocol, although binding was decreased after 120 min. The findings indicate that the VSM contractile response induced by the agent isolated from PD reflects VSM sodium pump inhibition, supporting its candidacy as a circulating regulator of the sodium pump.
尽管多方面的证据表明循环中的内源性洋地黄样因子(DLF)可能在钠敏感性高血压的发病机制中起作用,但这一问题仍存在争议。本研究旨在比较钾对容量扩张患者腹膜透析液(PD)中分离出的内源性DLF以及其他钠泵抑制剂(如哇巴因和蟾毒灵)引起的血管反应的影响,并以血清素作为特异性指标进行研究。将浴槽中钾(K +)浓度从2.7 mmol/L提高到10 mmol/L,可使由血清素预收缩的牛面动脉舒张,但在由哇巴因、蟾毒灵或PD中的内源性DLF预收缩的血管平滑肌(VSM)中会诱发继发性反常收缩反应。每种钠泵抑制剂引起的原发性收缩与反常继发性收缩反应的幅度之间存在很强的相关性。在实验方案所需的20分钟内,钾浓度的增加并未影响哇巴因结合,尽管120分钟后结合减少。研究结果表明,从PD中分离出的物质诱导的VSM收缩反应反映了VSM钠泵抑制,支持其作为钠泵循环调节因子的候选资格。