The effect of antihypertensive therapy on abnormal leucocyte sodium transport in essential hypertension

Sodium transport in leucocytes of essential hypertensives was studied in physiological media. Untreated hypertensives have depressed values for the total and ouabain-sensitive sodium efflux rate constant. Treatment with diuretics abolished this abnormality. These results are compatible with the presence of a circulating inhibitor of sodium transport in essential hypertension.     

Circulating inhibitor of sodium active transport in essential hypertension and volemic expansion

Circulating inhibitors of the Na+ pump have been proposed as participating in sodium excretion, extracellular and vascular volume regulation and as hypertensiogenic agents. The presence of digitalis-like compounds in human plasma has been investigated by measuring its ability to compete with tritiated ouabain for binding to the digitalis site of red blood cells. Their activities in plasma from either hypertensive or volume expanded patients were compared. High levels were found in plasma from 37 p. cent of the untreated patients with essential hypertension, 64 p. cent of patients with end-stage renal failure and 71 p cent of acromegalic patients in the hypersecreting phase. The patients of these two last classes have been selected as being normotensives and without family history of hypertension. An increased activity of the inhibitor should more likely be linked to the positive Na+ balance and the volemic expansion which characterise these last two diseases than to high blood pressure. The observations that the activity of the inhibitor is correlated with the plasma volume in acromegalic patients, it returns to normal values after hemodialysis in renal insufficiency or successful therapy of acromegaly and the decrease in its activity is proportional to the weight lost during dialysis in uremic patients, agree with this proposal.     

Alterations in sodium metabolism as an etiological model for hypertension

Summary An adequate matching for race, sex, stage of the menstrual cycle, family history of hypertension, and the amount of sodium and other electrolytes in the diet should be a prerequisite for valid conclusions when interpreting the erythrocyte concentration and fluxes of sodium in essential hypertensive patients in comparison with normal subjects. Alterations in intracellular sodium concentration and transmembrane sodium transport systems as causes of essential hypertension are postulated. This review article describes how this abnormal sodium and calcium metabolism translates into increased systemic vascular resistance through altered vasoactive responses and/or vasculature structural changes.     

Resistive heating is more effective than metallic-foil insulation in an experimental model of accidental hypothermia: A randomized controlled trial

STUDY OBJECTIVE: We study a resistive-heating blanket in a volunteer model of severe accidental hypothermia to evaluate differences in rates of rewarming, core temperature afterdrop, and body heat content and distribution during active and passive rewarming. METHODS: Eight volunteers participated in a crossover design on 2 days. The volunteers were anesthetized and cooled to 33 degrees C (91.4 degrees F); anesthesia was subsequently discontinued, and shivering was prevented with meperidine. On one randomly assigned day, the volunteers were rewarmed passively with reflective foil (passive insulation), whereas on the other they were covered with a carbon fiber-resistive heating blanket set to 42 degrees C (107.6 degrees F; active rewarming). Trunk and head temperature and heat content were calculated from core (tympanic membrane) temperature. Peripheral (arm and leg) tissue temperature and heat content were estimated by using fourth-order regressions and integration over volume from 30 tissue and skin temperatures. RESULTS: Core heat content increased 73+/-14 kcal (mean+/-SD) during 3 hours of active warming, but only 31+/-24 kcal with passive insulation, a difference of 41+/-20 kcal (95% confidence interval [CI] 27 to 55 kcal; P <. 001). Peripheral tissue heat content increased linearly by 111+/-16 kcal during active warming but only by 38+/-31 kcal during passive warming, a difference of 74+/-34 kcal (95% CI 50 to 97; P <.001). Consequently, total body heat increased 183+/-22 kcal during active warming but only 68+/-54 kcal with passive insulation, a difference of 115+/-42 kcal (95% CI 86 to 144 kcal; P <.001). Core temperature increased from 32.9 degrees C+/-0.2 degrees C to 35.2 degrees C+/-0. 4 degrees C during 3 hours of active warming, a difference of 2.3 degrees C+/-0.4 degrees C. In contrast, core temperature with foil insulation only increased from 32.9 degrees C+/-0.2 degrees C to 33. 8 degrees C+/-0.5 degrees C, a difference of only 0.8 degrees C+/-0. 4 degrees C. The difference in the core temperature increase between the two treatments was thus 1.5 degrees C+/-0.4 degrees C (95% CI 1. 2 degrees C to 1.7 degrees C; P <.001 between treatments). Active warming was not associated with an afterdrop, whereas the afterdrop was 0.2 degrees C+/-0.2 degrees C and lasted a median of 45 minutes (interquartile range, 41 to 64 minutes) with passive insulation. CONCLUSION: Resistive heating more than doubles the rewarming rate compared with that produced by reflective metal foil and does so without producing an afterdrop. It is therefore likely to be useful in the prehospital setting.     

Rebamipide enema is effective for treatment of experimental dextran sulfate sodium induced colitis in rats

We investigated therapeutic efficacy of rebamipide using dextran sulfate sodium (DSS) induced colitis model in rats. Three percent DSS solution was given to rats for 9 days. After that, we evaluated the drug efficacy on colitis sustained with continuous drinking of 1% DSS. Twice-daily treatment with 0.3% or 1% rebamipide for 14 days significantly ameliorated the stool abnormality in the colitis model, preferentially suppressed hematochezia. The colonic mucosal lesion, determined by Alcian blue staining on day 24, was significantly reduced by rebamipide enema in a dose-dependent manner. Either rebamipide or 5-aminosalycilic acid (5-ASA) enema treated once daily significantly ameliorated colitis. The minimum effective dose of rebamipide was 0.3% in once-daily treatment, and that of 5-ASA was 10%. In a mechanistic study, the epithelial cell sheet formation of the T84 colon cancer cell was measured as an increase in generation of trans-epithelial electrical resistance in vitro. Rebamipide accelerated the increase, while 5-ASA conversely suppressed it. These results suggest that rebamipide enema is effective for treatment of experimental ulcerative colitis (UC).     

Hypertonic sodium bicarbonate is effective in the acute management of verapamil toxicity in a swine model

STUDY OBJECTIVE: This study was conducted to determine whether hypertonic sodium bicarbonate would improve the hypotension associated with severe verapamil toxicity compared with volume expansion. METHODS: The study design used a nonblinded acute animal preparation. Twenty-four anesthetized and instrumented swine were poisoned with verapamil delivered at a rate of 1 mg/kg per hour for 10 minutes followed by incremental increases of 1 mg/kg per hour every 10 minutes until the endpoint of a mean arterial blood pressure of 45% of baseline was achieved. Animals alternately received either 4 mEq/kg of hypertonic sodium bicarbonate intravenously over 4 minutes or similar volumes of 0.6% sodium chloride in 10% mannitol (control). The main outcome parameter followed was mean arterial pressure. In addition, physiologic parameters including cardiac output, heart rate, pH, PCO (2), PO (2), plasma ionized calcium, sodium, and potassium were monitored. RESULTS: Verapamil toxicity, as defined by a mean arterial pressure of 45% of baseline, was produced in all animals following an average verapamil infusion dose of 0.6+/-0.12 mg/kg. This dose produced an average plasma verapamil concentration of 728.1+/-155.4 microgram/L, with no significant difference between groups. Swine treated with hypertonic sodium bicarbonate experienced a significant increase in mean arterial pressure (>50%) and cardiac output (>30%) over the first 20 minutes that slowly equilibrated with the control group over the remainder of the experiment. As expected, plasma sodium concentrations were elevated significantly in the sodium bicarbonate group while plasma potassium concentrations were decreased significantly. Finally, there was a significant decrease in plasma ionized calcium concentration in the sodium bicarbonate-treated group compared with controls. CONCLUSION: Hypertonic sodium bicarbonate reversed the hypotension and cardiac output depression of severe verapamil toxicity in a swine model.     

Assessment of red cell sodium transport in essential hypertension

Abnormal erythrocyte Na+ transport has been reported in patients with essential hypertension and some first-degree relatives. The two major techniques now employed for estimating Na+ transport--Na+/Li+ countertransport and Na+/K+ cotransport--are rather intricate and time consuming. Furthermore, the precise nature of the transport processes being measured is not clear. We have developed a simpler, more direct technique based on measurement of 22Na+ accumulation by erythrocytes. 22Na+ uptake by red cells from patients with essential hypertension averages twice normal. Indeed, of 21 patients with essential hypertension, only 2 patients had values within the upper end of the normal range. In 12 patients with secondary hypertension and no family history of essential hypertension, erythrocyte 22Na+ accumulation was within normal limits. Control experiments indicate that our technique for estimating red cell 22Na+ uptake is highly reproducible and shows little day-to-day variation. This procedure for the assessment of erythrocyte Na+ transport should be useful in differential diagnosis and the presymptomatic identification of individuals genetically prone to essential hypertension.     

Distribution of sodium in the tissues in experimental salt hypertension]

The distribution of sodium in the aortal wall, myocardium and skin of rats was studied by a tracer technique. An increase of the bound fraction of extracellular sodium was found in the aortal wall and skin of rats with hypertension produced by a 90-day salt load. A positive correlation was found between the content of bound sodium in the aorta and the arterial pressure level.     

Changes in Na,K-ATPase,sodium ion,and glucose transport in isolated enterocytes in an experimental model of malabsorption

Nippostrongylus brasiliensis infection of the rat resulted, at day 10 of infection, in decreased levels of jejunal enterocyte sodium-potassium-activated adenosine triphosphatase (Na,K-ATPase) and potassium-activated p-nitrophenyl phosphatase (K-pNPPase) activities. Parallel decreases occurred in active sodium efflux from jejunal enterocytes in the presence and absence of actively transported monosaccharides. Ileal enterocyte Na,K-ATPase and K-pNPPase activities were significantly increased, as was active sodium efflux. In contrast to controls, the presence of monosaccharides produced a stimulation of active sodium efflux from ileal enterocytes derived from infected rats. Enzyme and sodium transport changes in the jejunal enterocytes probably reflect cellular immaturity. Functional changes in ileal enterocytes probably represent a compensatory phenomenon.     

Mechanism of antihypertensive effect of dietary potassium in experimental volume expanded hypertension in rats

Dietary potassium supplementation lowers blood pressure (BP) and attenuates complications in hypertensive subjects, particularly those with the low renin volume expanded (LRVE) variety. We and others have shown that the plasma level of a digitalis like substance (DLS) is elevated in this type of hypertension. We therefore, examined the effect of increases in dietary potassium on the plasma level of endogenous DLS, myocardial and renal Na+, K+-ATPase (NKA) activities, BP, and renal excretory function in reduced renal mass (RRM)-salt hypertension in the rat, a classical model of LRVE hypertension. 70% RRM rats were divided in 4 groups, namely those consuming: 1) a sodium free and normal potassium (1.3% as KCl) diet (RRM-0 Na), 2) a normal sodium and normal potassium diet (RRM-NaK), 3) a normal sodium and high potassium (2 X normal) diet (RRM-Na2K), and 4) a normal sodium and 4 times normal potassium diet (RRM-Na4K). At the end of 4 weeks of dietary treatment, direct BP was recorded, plasma level of DLS determined by bioassay and with a radioimmunoassay for digoxin (DIF) and myocardial and renal NKA activities were measured. As expected, compared to RRM-0Na rats, RRM-NaK rats developed hypertension. BP increased significantly less in RRM-Na2K, whereas BP did not increase in RRM-Na4K rats. Hypertension in RRM-NaK rats was associated with an increase in plasma DLS and DIF and decrease in renal and myocardial NKA activities. DLS was increased (DIF was not changed) and myocardial NKA also decreased in rats consuming double potassium. However, quadrupling potassium in the diet (RRM-Na4K) normalized DLS and DIF and increased myocardial and renal NKA activities, compared to RRM-0Na rats. Also compared to RRM-0Na, water consumption, urinary volume excretion, sodium, and potassium increased in the other 3 groups, more so in RRM-Na4K rats. These data show that quadrupling the potassium in the diet prevents the BP increase in RRM rats and this is associated with diuresis/natriuresis and normalization of DLS, perhaps because the diuresis/natriuresis normalizes blood volume.     

Release of an active sodium transport inhibitor (ASTI) from rat hypothalamic cells in culture

To investigate the hypothesis whether the hypothalamus releases an active (ouabain-sensitive) sodium transport inhibitor, we cultured hypothalamic and cortical cells from day 17 fetal rats. Culture media from hypothalamic cells reduced the total erythrocyte sodium efflux rate constant from 0.487 +/- (SE) 0.014 to 0.408 +/- 0.013 (P less than 0.001), and the ouabain-sensitive rate constant from 0.305 +/- 0.015 to 0.240 +/- 0.016 (P less than 0.01). Hypothalamic media also showed a dose-dependent displacement of [3H]-ouabain-binding to erythrocyte membranes. Neither cortical nor conditioned media (incubated without cells) had any effect. Various well-characterized hormones of hypothalamic origin failed to inhibit sodium efflux rate constant. These studies demonstrate that fetal rat hypothalamic cells contain and release a factor which inhibits sodium transport in human erythrocytes.     

Effect of angiotensin on renal transport of sodium in renovascular hypertension

Eleven patients with renovascular arterial hypertension were studied, 9 of whom had unilateral renal artery stenosis and 2 bilateral renal artery stenosis.

Angiotensin increased sodium excretion in the contralateral kidney and did not change it in the stenotic one.

In bilateral stenosis angiotensin increased sodium excretion significantly in both kidneys.

The difference in response to angiotensin between patients with unilateral stenotic kidney and those with bilateral stenosis is apparently unrelated to arterial blood pressure distal to the arterial stenosis.