Hayashida T, Ohno Y, Otsuka K, Suzawa T, Shibagaki K, Suzuki H, Ikeda H, Saruta T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
J Hypertens. 2001 Sep;19(9):1643-50. doi: 10.1097/00004872-200109000-00017.
Increased Na+-H+ exchanger activity (NHE) has been reported as an intermediate phenotype in hypertensive subjects, particularly those with insulin resistance. To investigate whether NHE abnormality plays a role in hypertension, Wistar fatty rat (WFR) with overt obesity, hyperglycemia and marked hyperinsulinemia was examined.
WFR and Wistar lean rats (WLR) as a control (n = 12, each) were fed either with normal (0.38%) or high sodium (4% NaCl) diet for 12 weeks and then sacrificed to examine platelets NHE activity.
Mean arterial pressure (MAP) was higher in WFR than in WLR (113 +/- 4 versus 96 +/- 7 mmHg, P < 0.05) under a normal chow. Vmax values of NHE activity were significantly higher in WFR than in WLR. WFR fed with a high sodium diet showed higher MAP than those with a normal chow (128 +/- 3 versus 113 +/- 4 mmHg, P < 0.05). Though Km values were not different between WFR and WLR under a normal chow, both maximal transport rate (Vmax) and half maximal transport (Km) values were significantly higher in WFR with a high salt diet than those with a control diet. Vmax showed significant correlation with MAP, whereas Km values correlated with immunoreactive insulin (IRI) levels. Significant interaction between dietary sodium intake and the strain differences was observed both on blood pressure and on IRI levels by two-way analysis of variance (ANOVA).
WFR presented salt-sensitive blood pressure elevation. NHE activity was enhanced in WFR in correlation with the blood pressure. These results suggest that augmented NHE activity contributes to the development of salt-sensitive blood pressure elevation in WFR.
据报道,钠氢交换体活性(NHE)增加是高血压患者的一种中间表型,尤其是那些伴有胰岛素抵抗的患者。为了研究NHE异常是否在高血压中起作用,我们对明显肥胖、高血糖和显著高胰岛素血症的Wistar肥胖大鼠(WFR)进行了研究。
将WFR和作为对照的Wistar瘦大鼠(WLR)(每组n = 12)分别给予正常(0.38%)或高钠(4% NaCl)饮食12周,然后处死以检测血小板NHE活性。
在正常饮食条件下,WFR的平均动脉压(MAP)高于WLR(113±4对96±7 mmHg,P < 0.05)。WFR的NHE活性Vmax值显著高于WLR。给予高钠饮食的WFR的MAP高于给予正常饮食的WFR(128±3对113±4 mmHg,P < 0.05)。尽管在正常饮食条件下WFR和WLR的Km值没有差异,但高盐饮食的WFR的最大转运速率(Vmax)和半数最大转运(Km)值均显著高于对照饮食的WFR。Vmax与MAP呈显著相关,而Km值与免疫反应性胰岛素(IRI)水平相关。通过双向方差分析(ANOVA)观察到饮食钠摄入量与品系差异之间在血压和IRI水平上存在显著交互作用。
WFR表现出盐敏感性血压升高。WFR的NHE活性增强且与血压相关。这些结果表明,NHE活性增强有助于WFR中盐敏感性血压升高的发生发展。