Alex Forman

NaCl-Induced Renal Vasoconstriction in Salt-Sensitive African Americans Antipressor and Hemodynamic Effects of Potassium Bicarbonate

In 16 African Americans (blacks, 14 men, 2 women) with average admission mean arterial pressure (MAP, mm Hg) 99.9+/-3.5 (mean+/-SEM), we investigated whether NaCl-induced renal vasoconstriction attends salt sensitivity and, if so, whether supplemental KHCO3 ameliorates both conditions. Throughout a 3-week period under controlled metabolic conditions, all subjects ate diets containing 15 mmol NaCl and 30 mmol potassium (K+) (per 70 kg body wt [BW] per day). Throughout weeks 2 and 3, NaCl was loaded to 250 mmol/d; throughout week 3, dietary K+ was supplemented to 170 mmol/d (KHCO3). On the last day of each study week, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) using renal clearances of PAH and inulin. Ten subjects were salt sensitive (SS) (DeltaMAP >+5%) and 6 salt resistant (SR). In NaCl-loaded SS but not SR subjects, RBF (mL/min/1.73 m2) decreased from 920+/-75 to 828+/-46 (P<0.05); filtration fraction (FF, %) increased from 19. 4+/- to 21.4 (P<0.001); and renal vascular resistance (RVR) (10(3)xmm Hg/[mL/min]) increased from 101+/-8 to 131+/-10 (P<0.001). In all subjects combined, DeltaMAP varied inversely with DeltaRBF (r =-0.57, P=0.02) and directly with DeltaRVR (r = 0.65, P=0.006) and DeltaFF (r = 0.59, P=0.03), but not with MAP before NaCl loading. When supplemental KHCO3 abolished the pressor effect of NaCl in SS subjects, RBF was unaffected but GFR and FF decreased. The results show that in marginally K+-deficient blacks (1) NaCl-induced renal vasoconstrictive dysfunction attends salt sensitivity; (2) the dysfunction varies in extent directly with the NaCl-induced increase in blood pressure (BP); and (3) is complexly affected by supplemented KHCO3, GFR and FF decreasing but RBF not changing. In blacks, NaCl-induced renal vasoconstriction may be a pathogenetic event in salt sensitivity.

Sodium-Selective Salt Sensitivity Its Occurrence in Blacks

We tested the hypothesis that the Na+ component of dietary NaCl can have a pressor effect apart from its capacity to complement the extracellular osmotic activity of Cl− and, thus, expand plasma volume. We studied 35 mostly normotensive blacks who ingested a low-NaCl diet, 30 mmol/d, for 3 weeks, in the first and third of which Na+ was loaded orally with either NaHCO3 or NaCl, in random order (250 mmol/d). In subjects adjudged to be salt sensitive (n=18; &Dgr; mean arterial pressure: ≥5 mm Hg with NaCl load), but not in salt-resistant subjects (n=17), loading with NaHCO3 was also pressor. The pressor effect of NaHCO3 was half that of NaCl: mean arterial pressure (millimeters of mercury) increased significantly from 90 on low NaCl to 95 with NaHCO3 and to 101 with NaCl. The pressor effect of NaCl strongly predicted that of NaHCO3. As judged by hematocrit decrease, plasma volume expansion with NaCl was the same in salt-resistant and salt-sensitive subjects and twice that with NaHCO3, irrespective of the pressor effect. In salt-sensitive subjects, mean arterial pressure varied directly with plasma Na+ concentration attained with all Na+ loading. In salt-sensitive but not salt-resistant subjects, NaHCO3 and NaCl induced decreases in renal blood flow and increases in renal vascular resistance; changes in renal blood flow were not different with the 2 salts. Responses of renal blood flow and renal vascular resistance to NaHCO3 were strongly predicted by those to NaCl. In establishing the fact of “sodium-selective” salt sensitivity, the current observations demonstrate that the Na+ component of NaCl can have pressor and renal vasoconstrictive properties apart from its capacity to complement Cl− in plasma volume expansion.

Reduced Dietary Potassium Reversibly Enhances Vasopressor Response to Stress in African Americans

Acute vasopressor responses to stress are adrenergically mediated and hence potentially subject to differential modulation by dietary potassium and sodium. The greater vasopressor responsiveness in blacks compared with whites might then be consequent not only to a high dietary salt intake but also to a marginally reduced dietary potassium intake. Under controlled metabolic conditions, we compared acute vasopressor responses to cold and mental stress in black and white normotensive men during three successive dietary periods: (1) while dietary potassium was reduced (30 mmol K+/70 kg per day) and salt was restricted (10 to 14 days); (2) while salt was loaded (15 to 250 mmol Na+/70 kg per day) (7 days); and (3) while salt loading was continued and potassium was either supplemented (70 mmol K+/70 kg per day) (7 to 21 days) in 9 blacks and 6 whites or continued reduced (30 mmol K+/70 kg per day) (28 days) in 4 blacks (time controls). At the lower potassium intake, cold-induced increase in forearm vascular resistance in blacks was twice that in whites during both salt restriction and salt loading. Normalization of dietary potassium attenuated cold-induced increases in both forearm vascular resistance and systolic and diastolic blood pressures in blacks but only in systolic pressure in whites. In blacks but not in whites, normalization of dietary potassium attenuated mental stress-induced increases in systolic and diastolic pressures. In normotensive blacks but not whites, a marginally reduced dietary intake of potassium reversibly enhances adrenergically mediated vasopressor responsiveness to stress. That responsiveness so enhanced over time might contribute to the pathogenesis of hypertension in blacks.

Potassium intake and cardiovascular reactivity in children with risk factors for essential hypertension

OBJECTIVES Our study objectives were as follows: (1) to determine whether urinary excretion of potassium is lower in black than in white children, (2) to determine whether cardiovascular reactivity (CVR) varies inversely with dietary intake of potassium, and (3) to confirm that CVR is greater in black than in white children, and in children with a family history of hypertension than in those without such a history. STUDY DESIGN Baseline measurements included 24-hour urinary sodium, potassium, and creatinine levels and food intake (by questionnaire). Resting and stress blood pressure were measured during blood sampling, cold water foot immersion, and a video game before and after 1 week each of supplementation with potassium citrate, 1.5 mmol/kg per day, and placebo administered in random order. RESULTS Thirty-nine children aged 7 to 15 years were studied. White subjects had higher baseline excretion of potassium than black subjects (p < 0.001) and higher vegetable intake (p < 0.01), which were positively correlated (r = 0.53, p < 0.001). At baseline, the 24-hour urinary potassium/creatinine ratio varied inversely with diastolic CVR to the video game stressor in white children (r = -0.55, p = 0.02). Cardiovascular reactivity was not attenuated measurably by potassium supplementation compared with placebo. The CVR was greater in children with a family history of hypertension than in those without, but was not greater in black children than in white children. CONCLUSIONS The urinary potassium/creatinine ratio is higher in white than black children because their intake of vegetables is greater; dietary potassium intake may modulate CVR, particularly in white children with a family history of hypertension, but may need to be supplemented for more than 1 week to demonstrate attenuation of CVR; and a family history of hypertension may be a stronger predictor of enhanced CVR than is race.

What Initiates the Pressor Effect of Salt in Salt-Sensitive Humans? Observations in Normotensive African Americans

We tested the traditional hypothesis that an abnormally enhanced renal reclamation of dietary NaCl alone initiates its pressor effect (“salt sensitivity”). Under metabolically controlled conditions, we grouped 23 normotensive blacks as either salt-sensitive (SS) or salt-resistant (SR), depending on whether or not dietary NaCl loading did or did not increase mean arterial blood pressure (MAP) by ≥5 mm Hg. We determined whether dietary NaCl loading induces greater increases in external Na+ balance, plasma volume, and cardiac output in SS, compared with any in SR subjects, and differential changes in systemic vascular resistance (SVR) that could account for the pressor differences between SS and SR subjects. Using impedance cardiography, we measured cardiac output and SVR daily at 4-hour intervals throughout the last 3 days of a 7-day period of low NaCl intake (30 mmol per day) and throughout a subsequent 7-day period of NaCl loading (250 mmol per day). In the 11 SS subjects, compared with the 12 SR subjects, NaCl loading induced no greater increases in Na+ balance, body weight, plasma volume, and cardiac output. Yet, from days 2 to 7 of NaCl loading, changes of MAP in SS diverged progressively from those in SR. From days 2 to 4, progressive increases of MAP in SS subjects reflected importantly impaired decreases of SVR, as judged from “normal” decreases of SVR in SR subjects. In SS and SR subjects combined, changes in both MAP and SVR on day 2 strongly predicted changes in MAP on day 7. In many normotensive blacks, vascular dysfunction is critical to the initiation of a pressor response to dietary NaCl.