SELECTIVE SODIUM-SENSITIVITY IN SALT-SENSITIVE BLACKS

描述（由申请人提供）：有多次报道称，饮食中的Na +仅在以NaCI形式加载时才会引起“盐敏感性”（SS），即血压（BP）升高。然而，在正常血压和轻度高血压的中年非洲裔美国人（黑人）中，我们发现：1)在绝大多数SS患者中，膳食NaHCQloading诱导血压显著升高，其水平是膳食NaHCQloading诱导血压升高的三分之二。2)在具有这种“选择性Na +敏感性”（sNaS）的患者中，nahco -loading和NaCl-loading诱导肾血管阻力（RVR）相似的强劲增加。我们将验证这一假设：在大多数黑人中，NaCI的Na +成分选择性地诱导SS，主要是通过诱导外周血管收缩增加，从而增加RVR，并由血浆Na +浓度介导，其程度直接与血浆Na +浓度变化，但不需要像Guyton的假设那样，NaCI介导的血浆容量增加导致心输出量增加。我们将研究血压正常到轻度升高的健康、盐敏感和耐盐的黑人。在控制代谢条件下，饲粮NaCI和K +分别设定为30和50 mmol/70kg/d。在7天的对照期后，将在7天内立即添加250 mmol/d的钠盐。在每个受试者中，我们将测量NaCI和nahco3 - 10的影响：1)BP和Na +平衡（NAB），贯穿始终；2)对照期第7天和Na+加载第2、7天细胞外体积（ECV）、血浆体积（PV）和RVR；3)每日心输出量（CO）和总外周阻力（TPR）。该假说预测，在那些具有sNaS的人中：1)口服Na + -Ioading用盐会导致英国石油公司强劲的增长,RVR和TPR,先于任何增加公司。2)前将持续增加,他们和每个达到绝对值,直接与随之而来的血浆浓度的不同Na +诱导,而不是与伴随公司的价值观。3)NaHCO3-1oading不会引起更大,并可能诱发较小,增加光伏有限公司ECV和NaB比NaCl-loading诱导的抗盐科目。4)静脉给予高渗NaHCQ或NaCI超过2小时，会引起急性BP， RVR和TPR的增加，大于等摩尔但更大体积的低渗NaCI引起的急性BP， RVR和TPR的增加。5)血浆Na +浓度的急性升高可预测BP、RVR、TPR的急性升高程度。

DESCRIPTION (provided by applicant): It has repeatedly been reported that dietary Na + induces an increase in blood pressure (BP) i.e. elicits "salt-sensitivity" (SS) only when loaded as NaCI. However, in both normotensive and mildly hypertensive, middle-aged African-Americans (blacks), we find that: 1) In the great majority of those with SS, dietary NaHCQloading induces a robust increase in blood pressure that is fully two-thirds that induced by dietary NaCI loading. 2) In those with such "selective Na + sensitivity" (sNaS), NaHCO-Ioading and NaCl-loading induce similarly robust increases in renal vascular resistance (RVR). We will test this hypothesis: In most blacks, the Na + component of NaCI selectively elicits SS mainly by inducing an increase in peripheral vasoconstriction that increases RVR and is mediated by, and varies in extent directly with, the plasma concentration of Na +, but does not require, as the hypothesis of Guyton does, a NaCI-mediated increase in plasma volume that entrains an increase in cardiac output. We will study healthy, salt-sensitive and salt-resistant blacks with normal to mildly increased blood pressures. Under controlled metabolic conditions, dietary NaCI and K + will be set at 30 and 50 mmol/70kg/d, respectively. Immediately after a 7-day control period, a dietary Na-salt will be loaded, 250 mmol/d, over a 7-day period. In each subject, we will measure the effects both of NaCI and of NaHCO3-1oading on: 1) BP and Na + balance (NAB), throughout; 2) extracellular volume (ECV), plasma volume (PV) and RVR, on the 7th day of the control period and on the 2nd and 7th days of Na+-Ioading; 3) cardiac output (CO) and total peripheral resistance (TPR), daily. The hypothesis predicts that in those with sNaS: 1) Oral Na+-Ioading with either salt will induce robust increases in BP, RVR and TPR that precede any increases in CO. 2) The preceding increases will persist, and they, and the absolute values each attains, will vary directly with the concomitant plasma concentrations of Na +induced, but not with the concomitant values of CO. 3) NaHCO3-1oading will not induce greater, and may induce lesser, increases in PV, CO, ECV and NaB than those induced by NaCl-loading in salt-resistant subjects. 4) Either hypertonic NaHCQ or NaCI intravenously administered over a 2 hr-period, will induce acute increases in BP, RVR and TPR greater than those induced by an equimolar but larger volumes of hypotonic NaCI that are more PV-expanding. 5) The acute increases in plasma Na + concentration will predict the extent of acute increases in BP, RVR and TPR.