SELECTIVE SODIUM-SENSITIVITY IN SALT-SENSITIVE BLACKS

盐敏感型黑人的选择性钠敏感性

• 批准号: 6904647
• 负责人: Ralph Curtis Morris
• 金额: $ 32.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-15 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6904647
• 关键词: African American; blood pressure; body weight; clinical research; dietary potassium; dietary sodium; electrocardiography; electrolyte balance; glomerular filtration rate; hemodynamics; human subject; hypertension; kidney circulation; kidney function; nutrition related tag; sodium bicarbonate; sodium chloride; vasoconstriction

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.

描述（由申请人提供）：已经多次报道，膳食Na +诱导血压（BP）升高，即仅当以NaCl形式加载时才引起“盐敏感性”（SS）升高。 然而，在血压正常和轻度高血压的中年非裔美国人（黑人）中，我们发现：1）在绝大多数患有SS的人中，饮食中的NaHCQ负荷诱导血压的强烈升高，其完全是饮食中的NaCl负荷诱导的血压的三分之二。 2)在具有这种“选择性Na +敏感性”（sNaS）的那些中，NaHCO负载和NaCl负载诱导肾血管阻力（RVR）类似地稳健增加。 我们将测试这个假设：在大多数黑人中，NaCl的Na +组分主要通过诱导外周血管收缩增加来选择性地消除SS，外周血管收缩增加RVR，并且由Na +的血浆浓度介导，并且在程度上直接随Na +的血浆浓度变化，但不需要像盖顿的假设那样，NaCl介导的血浆容量增加，从而引起心输出量增加。 我们将研究血压正常至轻度升高的健康、盐敏感和耐盐黑人。 在受控代谢条件下，将饲料NaCl和K +分别设定为30和50 mmol/70 kg/d。 在7天对照期后，将立即在7天内加载250 mmol/d的膳食钠盐。 在每例受试者中，我们将测量NaCl和NaHCO 3 - 1负荷对以下各项的影响：1）血压和Na +平衡（NAB），全程; 2）细胞外容积（ECV）、血浆容积（PV）和RVR，在对照期的第7天和Na+负荷的第2天和第7天; 3）心输出量（CO）和总外周阻力（TPR），每日。 该假说预测，在sNaS患者中：1）口服任一盐的Na+-负载将诱导BP、RVR和TPR的强烈增加，其先于CO的任何增加。2）前述增加将持续，并且它们以及各自达到的绝对值将直接随着伴随的Na +诱导的血浆浓度而变化，3）NaHCO 3 - 1负荷不会引起耐盐受试者PV、CO、ECV和NaB的增加，而可能比NaCl负荷引起的增加更小。 4)无论是高渗NaHCQ还是NaCl静脉内给药2小时，都会引起BP、RVR和TPR的急性增加，其幅度大于等摩尔但体积更大的低渗NaCl（PV扩张更大）引起的增加。 5)血浆Na +浓度的急性升高可预测BP、RVR和TPR的急性升高程度。