We have investigated the relationship between plasma Na-K ATPase inhibitor activity (EDLS) and intracellular ions in 37 uremic hemodialysed hypertensive patients, and in 20 normotensive non uremic controls (NC). As compared with the NC population, significantly enhanced values for erythrocyte (RBC) Na, Ca, platelet cytosolic Ca and EDLS were observed in all the uremic patients tested just before a dialysis session, as well as a decrease in RBC Ca ATPase and in the platelet pH. In uremia, significant correlations have been noted between RBC Na and platelet Ca (r = 0.6) or systolic BP (r = 0.45); between platelet Ca and systolic blood pressure (r = 0.8) or diastolic BP (r = 0.5) and between EDLS and RBC Na, Ca or platelet Ca (r = 0.5). Anti-hypertensive treatment has no influence on these parameters. During dialysis, a significant decrease has been noted in RBC Na, Ca, platelet Ca, SBP (only in untreated patients) and EDLS and an increase in RBC Ca ATPase and platelet pH. These modifications are significantly correlated with the weight change.

Lipid linewidths were measured in the plasma proton spectra of young women. The individuals taking a contraceptive pill associating ethinyloestradiol and levonorgestrel or norethisterone were found with an average linewidth 2.5 Hz narrower than controls. As this drug regimen systematically induces an increase in plasma VLDL and a decrease in HDL/LDL ratio, our observation supports the theory that the Fossel test reflects plasma lipids abnormalities in cancer patients. © 1991 Academic Press, Inc.

The relationship between hypertension and atherosclerosis has been illustrated by epidemiological, clinical and experimental observations. Typical atherosclerotic lesions develop in arterial wall when hypercholesterolaemia is present. Hypertension aggravates these lesions by causing vascular structural changes.

In this study, omithine decarboxylase, the first and rate-limiting enzyme of the polyamine pathway, was used as a marker of the very early stages of cardiac hypertrophy. Our data show that ornithine decarboxylase is independently regulated by ventricular wall stress and adrenergic receptors, and support the theory that catecholamines have a pressure-independent trophic effect. The infusion of β2-adrenergic agonist, terbutaline, at 10-7 mol/l, did not affect the cardiac performance of isovolumic perfused rat hearts. Despite the lack of functional changes, ornithine decarboxylase activity, as assayed in vitro by 14C-ornithine decarboxylation, was markedly increased in both left and right ventricles. Further investigation showed that ornithine decarboxylase stimulation by catecholamines, unlike ornithine decarboxylase basal activity, was dependent on the extracellular calcium level. Furthermore, passive increases in ventricular wall stress in non-beating hearts also increased left ventricular ornithine decarboxylase activity.

The cardiovascular structural remodelling associated with psychogenic hypertension was investigated in genetically normotensive rats subjected to isolation stress. Male Wistar rats were stressed by intermittent social isolation and compared to control rats living in groups. The stressed rats had higher systolic blood pressures than the control rats throughout the study. After 1 week of isolation, ornithine decarboxylase activity, a marker for hypertrophy, was increased in the right ventricle of the stressed rats. After 6 weeks of intermittent isolation, the myocardium of the stressed rats was hypertrophied, involving both right and left ventricles. The aorta was also hypertrophied, whereas the tail artery remained unaffected. Later, after 12 weeks of isolation, the left ventricular hypertrophy persisted whereas the right ventricle and aorta returned to normal. It seems, therefore, that social stress hypertension is accompanied by very early structural changes, which affect at least the heart and the aorta, and cannot be directly linked to the severity or duration of hypertension.

The lack of effect of treatment of mild hypertension on the coronary heart disease has motivated researches for a better diagnosis of hypertension. One of the approaches presently under study uses the recording of ambulatory blood pressure using semi-automatic devices. The usefulness of these apparatus is however restricted by the lack of reference values recorded in normotensive control patients. We have recorded ambulatory blood pressure (PAA) in 24 normotensives, 22 untreated hypertensives and 45 treated hypertensive patients, and compared the data obtained to the blood pressure recorded during medical examination (PAC). If a good correlation is usually observed between PAA and PAC, very large and unpredictable discordances are frequently observed. No correlation is found between the difference PAA-PAC and the variability of PAA. This variability does not fully explain the difference observed between PAA and PAC. This variability expressed in mmHg increases with age and the level of BP. Ambulatory BP appears to be a very reproducible value which may allow to improve the definition of hypertension and there-fore the cardiovascular risk.

In hypertension, mainly low renin subjects, a plasma Na-K ATPase inhibitor has yet been demonstrated. Moreover, it has been established that the concentration of this activity may be modulated by variations of the sodium and water balance. In the present study, such an activity and its role has been searched in the plasma of young healthy normotensive population. Its potential natriuretic property has also been tested. Twenty male subjects, younger than 30, volunteered 3 very different sodium diets: normal (+/- 170 mM/d), very low (-20 mM/d) and very high sodium intake (+340 mM/d). At the end of each period, some clinical and biological parameters have been studied: blood pressure, weight, vascular resistances and reactivity to norepinephrine, 24 h natriuresis, and plasma renin activity. Furthermore, the plasma natriuretic activity has been tested after filtration of the plasma across different Amicon filters to measure the effect of plasma extracts from 500 to 10,000 daltons (LMW) on fractional sodium excretion (FENa) after injection of such extracts in vivo in rat renal artery. For detection of a plasma Na-K ATPase inhibitor activity, 1/5 th diluted fresh plasma and LMW extracts have been incubated with purified rabbit renal Na-K ATPase enzyme and compared with the activity of this enzyme without such an incubation of plasma. We have observed that when the amount of sodium in the diet is higher, weight, systolic blood pressure, and vascular reactivity to norepinephrine increase. In the same condition, there are greater natriuretic activity in the LMW extracts and Na-K ATPase inhibitor activity in fresh plasma and LMW extracts of the normotensive people.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline phosphatase, sucrase, Na+,K+-ATPase and Mg2+-ATPase specific activities of crude membrane fractions, prepared from duodenal, jejunal, ileal and colonic mucosa, have been estimated in three types of hypertensive rats: the spontaneously hypertensive rat (SHR), the DOCA-saline treated rat and the renovascular rat (Goldblatt one-kidney, one-clip rat; 1K-1C). Alkaline phosphatase and sucrase specific activities have been measured in purified jejunal brush-border membranes. When compared with its normotensive age-matched control (WKY rat), the SHR has a lower activity of alkaline phosphatase in duodenal and jejunal crude membrane fractions, whereas a higher activity in colonic Na+,K+-ATPase is recorded. In purified jejunal brush-border membranes, lower alkaline phosphatase activity and higher sucrase activity were found. These differences occur in the young prehypertensive SHR as well as in the adult animal. In the DOCA-treated rat, the only significant alteration in crude membrane fractions is a decreased Mg2+-ATPase activity at all regions of intestinal mucosa. In purified jejunal brush-border membranes both alkaline phosphatase and sucrase activities are increased at 4 or 7 weeks but especially at 13 weeks of hypertension. In the 1K-1C rat, no significant modification appears in crude membrane fractions or in purified jejunal brush-border membranes, but a decrease in alkaline phosphatase and in sucrase activities is probable after 13 weeks of hypertension. Since alterations of the intestinal enzymes are different in the three types of hypertensive rats it is concluded that the changes are not secondary to the hypertension condition. In the SHR, these alterations are present in the young prehypertensive animal.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of salt and/or volume depletion has been tested in 6 end-stage renal disease and 11 essential hypertensive patients (HTA) on red blood cell (RBC) ionic fluxes. Volume depletion promotes an increase in the RBC Na-K ATPase activity with, as a result, a significant decrease in intracellular sodium concentration [Na)ic). Moreover, a factor has been found in the plasma of uremic subjects which causes natriuresis when injected in rat renal arteries. The concentration of this factor decreases during dialysis in relation to the weight loss and the increase in the RBC Na-K pump activity. In essential hypertension, the effect of a low salt diet on the blood pressure is correlated with the improvement of RBC Na-K ATPase activity. These experiments illustrate the presence of a Na-K ATPase inhibitor in the plasma of these subjects, dependent on sodium and water balance.

The Na-K cotransport activity was measured in erythrocytes of 123 normotensive and 92 hypertensive patients, using the methodology described by Dagher and Garay. Large overlap of the values obtained in the two populations is observed, in such a way this laboratory test cannot be applied for the discrimination between primary and secondary hypertension. Moreover, the abnormalities described for the Na-K cotransport do not appear specific for primary hypertension. In this study, the influence of hypertensive heredity, but also obesity on this cotransport system could not be demonstrated. However, this transport activity is significantly decreased in patients with chronic renal failure, during treatment with oestro-progestatives or during the oestrogenic phase of the menstrual cycle. These data strongly suggest that the cotransport activity could be modified not only by the hypertensive familial predisposition but also by environmental and hormonal influences.

The effect of hemodialysis (acetate buffer) or hemofiltration on blood pressure, heart rate, peripheral vascular resistances, red blood cells ionic fluxes, and plasma natriuretic activity has been studied in six male patients treated for end-stage renal disease. The hemodynamic response to these two modes of treatment markedly differs. Whereas, peripheral resistances increase and heart rate is not affected during hemofiltration, a decrease in blood pressure, tachycardia, and vasodilation is observed during hemodialysis. However, in both therapeutic approaches, red blood cell ouabain-sensitive sodium-potassium pump activity increases in a similar way, and the plasmatic natriuretic activity decreases, whereas the vascular response to norepinephrine is reduced. All of these changes were strongly correlated to the amount of fluid removed. The natriuretic activity may thus play a role in the regulation of blood pressure and hemodynamic adjustments to fluid removal in chronic renal failure between two dialyses, but its action is not predominant during the dialysis session itself.