Kuriyama S, Kaguchi Y, Nakamura K, Hashimoto T, Sakai O
Second Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Pharmacol Res. 1992 Feb-Mar;25(2):155-65.
In order to elucidate the effect of serum and its differential characteristics in primary hypertension, we investigated the influence of serum from spontaneously hypertensive rats (SHR) on the cell membrane Na-K pump, Na-H antiport and passive K permeability of cultured vascular smooth muscle cells (VSMC) from SHR and Wistar-Kyoto rats (WKY). In the absence of serum, the Na-K pump activity, described as ouabain-sensitive 86Rb uptake (OS), was greater in the VSMC of the SHR than that of the WKY. Addition of serum to the quiescent VSMC stimulated the OS, of which activation was significantly greater with the SHR serum than with the WKY serum. Determination of intracellular Na concentrations in the presence of 1 mM ouabain showed that Na uptake in the absence of serum of the SHR VSMC was greater than that of the WKY VSMC. Subjecting the VSMC to rat serum stimulated Na uptake, which effect was more profound with SHR serum than with WKY serum. A greater stimulation of 5-(N,N-hexamethylene) amiloride(HMA)-sensitive Na uptake by SHR serum accounted for this difference. When the Na-K pump was active, intracellular Na concentrations were unchanged in the presence of serum. Furthermore, serum from either of the two strains produced a substantial increase in the washout rate constant of 86Rb washout (Ke), which effect was also larger in SHR serum than in WKY serum. In the absence of serum, basal Ke of the SHR VSMC was greater than that of the WKY VSMC. It is concluded that serum from SHR produced a more pronounced activation of the Na-K pump, Na-H antiport and passive K permeability in cultured VSMC. The study suggests that in addition to an innate augmented activity of Na-K transporters in the VSMC of SHR, there are humoral factors in SHR serum which elicit the stimulation of the Na-H antiport, leading to either the activation of the Na-K pump or secondary stimulation of passive K permeability across the cell membrane.
为了阐明血清及其差异特性在原发性高血压中的作用,我们研究了自发性高血压大鼠(SHR)血清对SHR和Wistar-Kyoto大鼠(WKY)培养的血管平滑肌细胞(VSMC)细胞膜钠钾泵、钠氢逆向转运体和被动钾通透性的影响。在无血清条件下,用哇巴因敏感的86Rb摄取量(OS)描述的钠钾泵活性,SHR的VSMC比WKY的更高。向静止的VSMC中添加血清可刺激OS,其中SHR血清引起的激活明显大于WKY血清。在1 mM哇巴因存在下测定细胞内钠浓度表明,无血清时SHR的VSMC钠摄取量大于WKY的VSMC。用大鼠血清处理VSMC可刺激钠摄取,SHR血清的这种作用比WKY血清更显著。SHR血清对5-(N,N-六亚甲基)氨氯吡脒(HMA)敏感的钠摄取有更大的刺激作用,这解释了这种差异。当钠钾泵活跃时,血清存在时细胞内钠浓度不变。此外,两种品系大鼠的血清均可使86Rb洗脱的洗脱速率常数(Ke)大幅增加,SHR血清的这种作用也比WKY血清更大。无血清时,SHR的VSMC的基础Ke大于WKY的VSMC。结论是,SHR血清在培养的VSMC中对钠钾泵、钠氢逆向转运体和被动钾通透性产生更明显的激活作用。该研究表明,除了SHR的VSMC中钠钾转运体先天活性增强外,SHR血清中还存在体液因子,可引发对钠氢逆向转运体的刺激,导致钠钾泵激活或继发刺激细胞膜的被动钾通透性。