Aging and interaction of natriuretic factors on renal and vascular sodium pump

我们对30例RH患者(男性15例，女性15例；55.6+/-1.3岁)进行了联合(赖诺普利/氨氯地平/氢氯噻嗪)治疗的研究。盐负荷(SL)通过静脉滴注1000mL生理盐水进行。1个小时。使用Fineter Pro设备注册心跳对心跳BP。用SPhygmoCor PX脉搏波传导速度(PWV)测定仪测量动脉硬度。用荧光免疫法和红细胞膜NKA活性测定血清MBG水平，在无和存在抗MBG单抗(MAb)体外治疗的情况下进行测量。 SL患者2小时内出现收缩压和舒张压升高(175+/-5vs.152+/-3和101+/-2vs.90+/-2，P均<0.01)，血浆MBG升高(0.48+/-0.06vs.0.31+/-0.05nmoL/L)，NKA抑制(1.49+/-0.09vs.2.11+/-0.07umol PI/ml/hr；P&lt；0.01)。抗MBG单抗体外恢复NKA(2.7+/-0.1umol PI/ml/hr；P&lt；0.01)。在男女患者中，SL的升压反应幅度与MBG水平和NKA活性无关，但在男性患者中，MBG引起的NKA抑制和SL刺激的MBG幅度与PVW呈正相关(分别为r=0.55，P=0.03和r=0.51，P=0.03)，而在女性患者中无相关性(分别为r=0.15，P=0.57和r=0.22，P=0.41)。在男女患者中，MBG诱导的NKA抑制程度与年龄呈正相关(r=0.45；P=0.006)。 这些结果表明，在男性顽固性高血压患者中，MBG诱导的NKA抑制程度与BP本身的盐敏感性无关，而与患者的年龄和PVW有关，PVW是血管僵硬的主要特征，是心血管老化的主要特征。

We studied 30 patients (15 males and 15 females; 55.6 +/- 1.3 yrs) with RH on a combined (lisinopril/amlodipine/hydrochlorothiazide) therapy. Salt loading (SL) was performed via infusion of 1000 mL saline i.v. for 1 hour. Beat-to-beat BP was registered using Finometer Pro device. Arterial stiffness was measured by Sphygmocor Px device with a calculation of pulse wave velocity (PWV). Levels of MBG were estimated by fluoroimmunoassay and by activity of NKA in erythrocytes at baseline and following SL, measured in the absence and in the presence of a monoclonal anti-MBG antibody (mAb) ex-vivo treatment. Within 2 hrs of SL patients exhibited elevation of systolic and diastolic BP (175 +/- 5 vs. 152 +/-3 and 101 +/- 2 vs. 90 +/- 2 mmHg, both P<0.01), increase in plasma MBG (0.48 +/- 0.06 vs. 0.31 +/- 0.05 nmol/L), and NKA inhibition (1.49 +/- 0.09 vs. 2.11 +/- 0.07 umol Pi/ml/hr; P<0.01). Anti-MBG mAb ex-vivo restored NKA (2.7 +/- 0.1 umol Pi/ml/hr; P<0.01). In patients of both sexes magnitude of pressor response to SL did not correlate with the levels of MBG and with NKA activity, but magnitude of MBG-induced NKA inhibition and of SL-stimulated MBG was positively associated with PVW in male (r=0.55, P=0.03, and r=0.51, P=0.03, respectively), but not in female subjects (r=0.15, P=0.57, and r=0.22, P=0.41, respectively). In patients of both sexes magnitude of MBG-induced NKA inhibition was positively associated with age (r=0.45; P=0.006). These results indicate that in male patients with resistant hypertension magnitude of MBG-induced NKA inhibition associates not with the salt-sensitivity of BP per se, but with age of patients and with PVW, which characterizes vascular stiffness, a major feature of cardiovascular aging.