SELECTIVE SODIUM-SENSITIVITY IN SALT-SENSITIVE BLACKS

描述(由申请人提供)：曾多次报道，饮食中的Na+会引起血压(BP)升高，即只有当摄入NaCI时才会引起“盐敏感性”(SS)。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SS患者中，饮食NaHCQ负荷导致血压强劲上升，足足是饮食NaCI负荷引起的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，NaHCO2负荷和NaCl2负荷同样引起肾血管阻力(RVR)的显著增加。我们将检验这一假说：在大多数黑人中，NaCI的Na+成分选择性地引起SS，主要是通过诱导外周血管收缩增加而增加RVR，并受血浆Na+浓度的调节，并在程度上直接与血浆Na+浓度变化，但不需要像Guyton假说那样，由NaCI介导的血浆容量增加，从而导致心输出量的增加。我们将研究血压正常到轻度升高的健康、盐敏感和耐盐黑人。在受控代谢条件下，日粮NaCI和K+分别设定为30和50 mmol/70 kg/d。在7天的控制期之后，立即在7天的期间内摄入250 mmo1/d的食盐。在每个受试者中，我们将测量NaCI和NaHCO3-1负荷对以下方面的影响：1)血压和Na+平衡(NAB)，贯穿始终；2)细胞外容量(ECV)，血浆容量(PV)和RVR，在控制期的第7天，Na+-负荷的第2天和第7天；3)心输出量(CO)和总外周阻力(TPR)，每天。该假说预测，在那些有SNAs的人中：1)口服Na+-负荷任何一种盐都会在CO增加之前诱导BP、RVR和TPR的强劲增加。2)上述增加将持续存在，并且它们及其所达到的绝对值将与伴随的Na+诱导的血浆浓度成正比，而与伴随的CO值无关。3)在耐盐性较强的受试者中，NaHCO3-1负荷不会引起更大的PV、CO、ECV和NAB的增加，而可能引起更小的增加。4)静脉注射高渗NaHCQ或NaCI 2小时后，BP、RVR和TPR的急剧增加均大于等摩尔但体积较大的低渗NaCI所致的血压、RVR和TPR的急剧增加，后者更具PV扩张性。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。

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.