Blood pressure responses to 1 week of low-salt (20 mmol sodium/d) and high-salt (300 mmol sodium/d) intake were investigated in a single-blind randomized study in 163 white, nonobese normotensive subjects (65 women and 98 men; mean age, 38±1.2 years). The individuals were classified as salt sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high-salt intake, as salt resistant when mean arterial blood pressure changed by less than 5 mm Hg, and as "counterregulator" when mean arterial blood pressure fell by at least 5 mm Hg during the high-salt diet. Reexamination of 31 subjects showed that this approach to the testing of salt sensitivity was reliable and reproducible. Thirty subjects (18.4%) were classified as salt sensitive, 108 (66.3%) as salt resistant, and 25 (15.3%) as counterregulators. Multiple regression analysis revealed that age, body weight, and family history of hypertension contributed significantly to the change in blood pressure after the diets. Salt sensitivity was more frequent in older subjects and in those with a positive family history of hypertension. An increase in blood pressure after salt restriction was more likely in younger individuals and in those with a negative family history of hypertension. Plasma renin activity and plasma aldosterone concentrations were lower in salt-sensitive compared with salt-resistant and counterregulating subjects. The rise in plasma renin activity during salt restriction was most pronounced in counterregulating subjects. Plasma norepinephrine concentrations were not different among the groups. Plasma levels of atrial natriuretic peptide increased during high-salt intake in all groups, the rise being most pronounced in salt-sensitive subjects. The increase in blood pressure during salt restriction in counterregulating subjects may be partially due to an overstimulation of the renin-angiotensin system. The exaggerated response of the secretion of atrial natriuretic peptide to high-salt intake in salt-sensitive subjects may point to an impaired capability of the kidney to excrete a salt load. 7 It has been assumed recently that the effect of a concerted health care program directed toward lowering salt intake of the general population would be extremely small. 6 The blood pressure response to sodium chloride is heterogeneous, at least during relatively short-term changes in salt intake. Salt sensitivity, defined as a significant rise in blood pressure when individuals switch from a low to a high sodium chloride intake, is seen in a considerable number of patients with essential hypertension and, although less frequent, in normotensive subjects.8 On the other hand, some individuals increase their blood pressure with sodium depletion 910 and therefore could be at higher risk when ingesting a salt-restricted diet.Little attention has focused so far on this issue. This may partially be due to the design of most of the previous studies dealing with salt sensitivity in which subjects reacting to low-salt intake with no change or a rise in pre...

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To study the physiological role of the bidirectionally operating, furosemide-sensitive Na+/K+ transport system of human erythrocytes, the effect of furosemide on red cell cation and hemoglobin content was determined in cells incubated for 24 hr with ouabain in 145 mM NaCl media containing 0 to 10 mM K+ or Rb+. In pure Na+ media, furosemide accelerated cell Na+ gain and retarded cellular K+ loss. External K+ (5 mM) had an effect similar to furosemide and markedly reduced the action of the drug on cellular cation content. External Rb+ accelerated the Na+ gain like K+, but did not affect the K+ retention induced by furosemide. The data are interpreted to indicate that the furosemide-sensitive Na+/K+ transport system of human erythrocytes mediates an equimolar extrusion of Na+ and K+ in Na+ media (Na+/K+ "cotransport"), a 1:1 K+/K+ (K+/Rb+) and Na+/Na+ "exchange" progressively appearing upon increasing external K+ (Rb+) concentrations to 5 mM. The effect of furosemide (or external K+/Rb+) on cation contents was associated with a prevention of the cell shrinkage seen in pure Na+ media, or with a cell swelling, indicating that the furosemide-sensitive Na+/K+ transport system is involved in the control of cell volume of human erythrocytes. The action of furosemide on cellular volume and cation content tended to disappear at 5 mM external K+ or Rb+. The in vivo red cell K+ content was negatively correlated to the rate of furosemide-sensitive K+ (Rb+) uptake, and a positive correlation was seen between mean cellular hemoglobin content and furosemide-sensitive transport activity. The transport system possibly functions as a K+ and water-extruding mechanism under physiological conditions in vivo. The red cell Na+ content showed no correlation to the activity of the furosemide-sensitive transport system.

mean systolic and diastolic pressures ( ± 1 SD) after recumbency were 164 ± 24 and 104 ± 11 mm Hg, respectively.Of the 18 essential hypertensive patients included in the study, six were women (38 to 60 years of age) and 12 were men (26 to 58 years old) (mean age ± 1 SD = 43 ± 12). All had normal intravenous (i.v.) pyelograms and renal angiotomograms as well as normal plasma creatinine values. In all patients, plasma renin activity (PRA) was measured 3 along with its change upon administration of furosemide and orthostatic stress. A case of hypertension was considered to be of the low renin type when both the basal PRA was below 1 ng angiotensin I • ml plasma" 1 • hr" 1 and the PRA rose less than twofold upon stimulation with 40 mg furosemide (i.v.) plus active orthostasis. The six lowrenin patients had a basal PRA of 0.85 ± 0.34 ng • ml"' • hr"', which was almost unchanged after furosemide plus 2 hours of orthostasis (1.27 ± 0.24). The remaining hypertensive patients exhibited a basal and stimulated PRA of 2.26 ± 1.06and5.5 ± 3.8ng«ml« hr, respectively, as compared to the values of 1.14 ± 0.68 and 9.4 ± 6.5 ng» ml"' • hr" 1 in a control group of 28 normotensive individuals (mean values ± 1 SD). All patients, including the six showing a classical lowrenin type of hypertension, had normal plasma aldosterone levels and normal urinary aldosterone excretion, respectively. The five patients with renal hypertension included in the study (two women and three men, mean age 47 ± 15 years) had blood pressures of 173 ± 26 (systolic) to 103i ± 6 mm Hg (diastolic). They showed disturbances of renal function with plasma creatinine levels above 1.5 mg • dl"1 . In two cases, intrarenal vascular stenosis was verified by angiography, two patients showed a unilaterally atrophic kidney, and one had undergone a unilateral pole resection.The control group consisted of seven women (aged 26 to 50 years) and 31 men (aged 26 to 55 years), recruited among apparently healthy members of our departments (mean age and mean blood pressure were 37 ± 9 years and 123 ± 12 to 80 ± 9 mm Hg, respectively). The probands were questioned with respect to renal disease and family history of hypertension. Two individuals with positive familial history of essential hypertension were not excluded from the study. The control group thus comprised a similar percentage of individuals genetically predisposed to essential hypertension as an unselected population. The Uptake lestFor the uptake assay, 10 ml of blood was drawn into Na + heparin. Hemoglobin and hematocrit were determined in whole blood to obtain the mean cellular hemoglobin content (MCHC) needed to calculate uptake rates referring to 1 ml of original cells.The buffy coat and plasma were removed after centrifugation (4500 X g) and the erythrocytes were washed 3 times in a medium containing 150 mM choline chloride, 5 mM glucose, 1 mM phosphoric acid, 10 mM morpholinopropane sulfonic acid (MOPS), and sufficient tris-(hydroxymethyl)-aminomethane (Tris) to yield a pH of 7.4 at 37°C (310 mOsm • kg H 2 O -')...

Red cell Na+ and K+ content and transport were studied in Sprague-Dawley rats in the course of a dietary K+ depletion ranging 1-6 wk. Plasma K+ fell to below 2 mM, and red cell K+ decreased. Cellular Na+ rose due to an increase of the Na+ leak. Inward Rb+ and outward Na+ transport by the Na+-K+ pump (determined at 2 mM external Rb+) were accelerated by the rise in cell Na+ concentration. K+ depletion caused a cation deficit of up to 30% of total red cell Na+ plus K+ and a consecutive cell shrinkage with an increase in mean cellular hemoglobin content (MCHC). The cell shrinkage, in turn, was paralleled by up to a 10-fold increase in the maximum capacity of the furosemide-sensitive, chloride-dependent Na+-K+ cotransport system. This system participated with up to 50% of the total K+ movements across the red cell membrane in severe K+ deficiency. In normal cells shrunken by osmotic means, Na+-K+ cotransport was similarly accelerated severalfold, indicating that the cell shrinkage occurring during K+ depletion is a major factor inducing the changes in Na+-K+ cotransport. However, a second unknown factor is also involved. It is concluded that in the rat, not only genetic but also environmental parameters contribute in determining the actual activity of the red cell Na+-K+ cotransport system. The cell volume and MCHC must be considered when judging Na+ and K+ transport changes observed in rat erythrocytes under various pathophysiological conditions.