RENAL EFFECTS OF DIETARY CHLORIDE IN AFRICAN-AMERICANS

膳食氯化物对非裔美国人肾脏的影响

• 批准号: 6351617
• 负责人: Ralph Curtis Morris
• 金额: $ 25.43万
• 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 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6351617
• 关键词: African American; bicarbonates; blood pressure; chloride ion; clinical research; dietary constituent; dietary potassium; glomerular filtration rate; hemodynamics; human subject; hypertension; kidney circulation; kidney function; nutrition related tag; vasoconstriction

We recently reported that when dietary potassium was controlled at a marginally deficient intake not uncommon in many African- Americans (blacks), 30 mmol/d, salt sensitivity occurred in the majority of normotensive blacks but in relatively few normotensive Caucasian-Americans (whites), and on average was more severe in blacks. In a subsequent study of normotensive and mildly hypertensive black men consuming a diet marginally deficient in potassium, we observed that in those who were salt- sensitive, dietary NaCl loading induced a renal vasoconstrictive dysfunction in which renal blood flow (RBF) decreased, renal vascular resistance (RVR) and filtration (FF) increased, and glomerular filtration rate trended upward. The changes in mean arterial pressure induced by dietary NaCl varied inversely with those induced in RBF and directly with those in RVR and FF. In those blacks who were not salt-sensitive, renal dysfunction was not observed with NaCl loading. Since dietary loading of sodium citrate (and other non-Cl sodium salts) fails to induce a pressor response in patients with salt-sensitive hypertension, sodium citrate might also fail to induce a renal vasoconstrictive dysfunction in normotensive salt-sensitive blacks. We anticipate this finding, and will interpret it as evidence suggesting that the pressor effect induced in blacks by NaCl loading requires the induction of a renal vasoconstrictive dysfunction, which in turn requires the Cl- component of loaded NaCl. We have recently reported that in the stroke-prone spontaneously hypertensive rat fed a normal NaCl diet, supplemental KCl induced a persisting exacerbation of hypertension, renal vasculopathy and strokes, whereas supplemental KHCO3 had opposite effects. When this rat was NaCl-loaded, supplemental KCl, but not KHCO3, further exacerbated hypertension and the renal vasculopathy, increased the frequency of strokes, and within hours induced a reduction in urinary creatinine excretion. In normotensive and mildly hypertensive blacks fed a normal NaCl diet (150mmol/d) just adequate in potassium (45 mmol/d), we will determine whether KCl and K-citrate (100 mmol/d) supplemented for 14 days have differing pressor and renal hemodynamic effects. We anticipate that both supplemented potassium salts will induce a decrease in blood pressure, but that a lower RBF and a higher RVR and FF will attend supplemental KCl. We will interpret such findings as suggesting that the Cl component of KCl can exert a renal vasoconstrictive and potentially renopathic effect despite a concomitant decrease in blood pressure.

我们最近报道，当饮食中的钾被控制在一个在许多非裔美国人(黑人)中并不罕见的轻微不足的摄入量时，大多数正常血压的黑人(白人)会出现盐敏感性，但相对较少的正常血压的高加索美国人(白人)会发生盐敏感性，平均而言，黑人的盐敏感性更严重。在随后对血压正常和轻度高血压的黑人男性进行的一项研究中，我们观察到，在那些对盐敏感的人中，饮食中的氯化钠负荷导致了肾脏血管收缩功能障碍，其中肾脏血流量(RBF)减少，肾血管阻力(RVR)和滤过率(FF)增加，肾小球滤过率呈上升趋势。食盐引起的平均动脉压变化与RBF的变化成反比，与RVR和FF的变化成正比。在那些对盐不敏感的黑人中，在氯化钠负荷下没有观察到肾功能障碍。由于饮食摄入柠檬酸钠(和其他非氯钠盐)不能在盐敏感型高血压患者中诱导升压反应，柠檬酸钠也可能无法在血压正常的盐敏感型黑人中诱导肾血管收缩功能障碍。我们预料到这一发现，并将其解释为证据表明，氯化钠负荷引起的黑人升压效应需要诱导肾脏血管收缩功能障碍，而这反过来又需要负荷的氯化钠的氯-成分。我们最近报道，在易中风的自发性高血压大鼠中，补充氯化钾会导致高血压、肾血管病变和中风的持续恶化，而补充碳酸氢钾则有相反的效果。当这只大鼠处于氯化钠负荷时，补充KCl而不是KHCO3，进一步加剧了高血压和肾脏血管病变，增加了中风的频率，并在数小时内导致尿肌酐排泄减少。在正常血压和轻度高血压的黑人中，喂食正常的氯化钠饮食(150 mmol/d)，只摄入适量的钾(45 mmol/d)，我们将确定补充14天的氯化钾和柠檬酸钾(100 mmol/d)是否有不同的升压和肾脏血流动力学影响。我们预计两种补充钾盐都会引起血压下降，但补充KCl时会出现较低的RBF和较高的RVR和FF值。我们将解释这样的发现，即尽管伴随着血压的降低，KCl中的氯成分可以发挥肾脏血管收缩和潜在的肾脏病变作用。