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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Special Emphasis Panel (ZRG1-CCVS (01))
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Barouch, Winifred
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
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Kurtz, Theodore W; DiCarlo, Stephen E; Pravenec, Michal et al. (2018) Testing Computer Models Predicting Human Responses to a High-Salt Diet. Hypertension 72:1407-1416
Kurtz, Theodore W; DiCarlo, Stephen E; Pravenec, Michal et al. (2018) Functional foods for augmenting nitric oxide activity and reducing the risk for salt-induced hypertension and cardiovascular disease in Japan. J Cardiol 72:42-49
Kurtz, Theodore W; DiCarlo, Stephen E; Morris Jr, R Curtis (2016) Logical Issues With the Pressure Natriuresis Theory of Chronic Hypertension. Am J Hypertens 29:1325-1331
Morris Jr, R Curtis; Schmidlin, Olga; Sebastian, Anthony et al. (2016) Vasodysfunction That Involves Renal Vasodysfunction, Not Abnormally Increased Renal Retention of Sodium, Accounts for the Initiation of Salt-Induced Hypertension. Circulation 133:881-93
Kurtz, Theodore W; DiCarlo, Stephen E; Pravenec, Michal et al. (2016) An alternative hypothesis to the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension. Kidney Int 90:965-973
Schmidlin, Olga; Tanaka, Masae; Sebastian, Anthony et al. (2010) Selective chloride loading is pressor in the stroke-prone spontaneously hypertensive rat despite hydrochlorothiazide-induced natriuresis. J Hypertens 28:87-94
Schmidlin, Olga; Forman, Alex; Sebastian, Anthony et al. (2007) Sodium-selective salt sensitivity: its occurrence in blacks. Hypertension 50:1085-92
Schmidlin, Olga; Sebastian, Alex Forman Anthony; Morris Jr, R Curtis (2007) What initiates the pressor effect of salt in salt-sensitive humans? Observations in normotensive blacks. Hypertension 49:1032-9
Morris Jr, R Curtis; Schmidlin, Olga; Frassetto, Lynda A et al. (2006) Relationship and interaction between sodium and potassium. J Am Coll Nutr 25:262S-270S
Schmidlin, Olga; Tanaka, Masae; Bollen, Andrew W et al. (2005) Chloride-dominant salt sensitivity in the stroke-prone spontaneously hypertensive rat. Hypertension 45:867-73

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