Erythrocyte sodium-lithium countertransport in primary and renal hypertension: relation to family history

Sodium-lithium countertransport (Na-Li CT) has been reported to be increased in essential hypertension (EHT) but the nature and degree of distinction from normal controls in unclear. Of 44 unselected patients with EHT in the hospital hypertension clinic 36% had Na-Li CT greater than the normal control range and 70% of these had a family history of hypertension. Almost all the patients with normal Na-Li CT had no family history of hypertension. Analysis of variance showed that raised Na-Li CT was related to both a family history of hypertension and a family history of a cardiovascular event. Of 23 patients with hypertension secondary to renal disease, 43% had Na-Li CT greater than the normal control range and raised Na-Li CT was related to both a family history of hypertension and a family history of cardiovascular event in the same way as EHT. Raised Na-Li CT was not characteristic of EHT but identified a subgroup of patients with EHT and a family history of hypertension, some of whom also had renal disease.     

Erythrocyte Na+-H+ exchanger and Na+-Li+ countertransport activity in primary aldosteronism

Abstract. Several authors have described increased Na-H exchanger activity in essential hypertension but no data are available in secondary forms of hypertension such as primary aldosteronism. We measured Na-H exchanger kinetics together with Na-Li countertransport V _max in the erythrocytes of eight patients with primary aldosteronism and in 15 normotensive control subjects. Plasma aldosterone, plasma renin and plasma potassium were also evaluated. Na-H exchanger V _max appear to be increased in patients with primary aldosteronism and Hill's n , an index of co-operativity amongst intracellular proton binding sites, was significantly lower in patients than in controls. No statistically significant differences were found between affinity for intracellular protons (K50%) and for Na-Li countertransport V _max between the two groups studied. We were unable to find any correlations between Na-H exchanger V _max and Na-Li countertransport V _max in the two groups considered as a whole. From the present data Na-H exchanger overactivity would not appear to be a specific feature of essential hypertension but seems to be characteristic in patients with primary aldosteronism.     

The relation of arterial pressure and the rate of Na-Li countertransport in a representative subsample of the population of Moscow residents

A study was made of the relationship between Na-Li countertransport and arterial blood pressure in 95 persons selected at random from the representative sample (n = 1716) of the population of one of the districts of Moscow. Of these, 34 persons turned out to be normotensive, 15 had borderline hypertension, 44 stable essential hypertension, and 2 persons presented with secondary hypertension. A positive correlation was found between countertransport and age and weight, determining 20.4% of interindividual variability of countertransport values. The mean value of countertransport in the hypertension group appeared much higher than in the normotensive group, both without and with regard to the correlating parameters. Repeated examinations demonstrated that the countertransport value in each person remained unchanged for two years. A nonlinear correlation was discovered between countertransport and arterial blood pressure. The rate of countertransport is not related to arterial blood pressure (low and high values). A dramatic change in the countertransport values occurred within a narrow borderline range of arterial blood pressure.     

The effect of hemosorption on the indices of the structural-functional status of the erythrocyte membranes in arterial hypertension patients

A study was made of the stability of the parameters of 2 membranous tests, used in the differential diagnosis of some forms of arterial hypertension, under the influence of hemoperfusion, an extracorporeal treatment method. One of these tests consists in the measurement of the Na-Li countertransport velocity across the erythrocytic membrane. It allows revealing functional disorders in ion transport across the cellular membranes. The second one involves the determination of monoclonal antibody (mon Ab) binding to the fragmented erythrocytic membranes. The test enables recording the structural changes that occur in the erythrocytic membranes. Before and after hemoperfusion the velocity of Na-Li countertransport was measured in 8 patients suffering from arterial hypertension whereas mon Ab binding to the fragmented erythrocytic membranes in 6 patients. After hemoperfusion all the patients manifested an increase of the velocity of Na-Li countertransport (by 15 to 108% as compared to the initial). On the other hand, after that procedure the patients with arterial hypertension did not demonstrate any appreciable alterations in mon Ab binding to the fragmented erythrocytic membranes. Thus, the membranous test (mon Ab binding to the fragmented erythrocytic membranes) reflecting the structural characteristics of the erythrocytic membrane appears more "rigid" and stable as compared to Na-Li countertransport reflecting the functional properties of the erythrocytic membrane, which, as it was to be expected, respond more readily to different external effects.     

The information value of membrane tests in the diagnosis of hypertension

The information content of the Na-Li transport test and of immunochemical test as a method of the diagnosis of essential hypertension was subjected to statistical analysis. The specificity, sensitivity and effectiveness of both these tests were determined. Comparative analysis of the information content of the Na-Li transport test and immunochemical test demonstrated that they are fit for differential diagnosis between essential hypertension and renal hypertensions.     

Whole blood storage solution for erythrocyte sodium and sodium-lithium countertransport rate determination

A solution consisting of heparinized and buffered isosmolar magnesium chloride is described in which whole blood may be stored for preservation of erythrocyte sodium (Na) and membrane sodium-lithium countertransport (Na-Li CT). Correlation (r) of fresh versus 24-h stored erythrocytes for Na was 0.990 (y = 0.30 + 0.956x) and for Na-Li CT was 0.995 (y = -0.014 + 1.022x). Na-Li CT rate was preserved in the storage solution for up to five days and erythrocyte Na concentration for at least 24 h. The solution should find application in epidemiological studies of erythrocyte Na and Na-Li CT rate in human essential hypertension as the blood specimens require no centrifugation or erythrocyte washing procedures prior to laboratory analysis.     

Detection of concomitant pathology in patients with arterial hypertension by structural and functional changes of erythrocyte membranes

The values of the Na-Li+ countertransport rate and the degree of monoclonal antibody binding with the erythrocyte membranes were compared in patients with different forms of arterial hypertension (AH) to identify combined pathology and the precursors of surgery effectiveness. Among the 27 examined AH patients 7 underwent surgery in accordance with the initial clinical diagnosis. The membrane tests helped to detect 3 patients with combined pathology: chronic pyelonephritis or chronic diffuse glomerulonephritis in combination with AH. Thus, the membrane tests were found to supplement each other in the assessment of surgery effectiveness and the perspectives for identification of combined pathology in patients with symptomatic AH of renal genesis.     

Exogenous factors influencing the human erythrocyte sodium–lithium countertransport system

It has recently been found that the Na+-Li+ countertransport across the human erythrocyte membrane is increased in patients with essential hypertension. We investigated the influence of hypokalaemia, oral contraceptives, diabetes mellitus and essential hypertension on the activity of this transport system. Normal values for the maximal Na+-Li+ transport rate were 0.25 +/- 0.08 mmol l-1 h-1 (males, n = 18) and 0.23 +/- 0.06 (females, n = 14). We found elevated values in women taking oral contraceptives (0.34 +/- 0.07, n = 10, P less than 0.001), in patients with chronic hypokalaemia due to diuretic or laxative abuse (0.41 +/- 0.16, n = 13, P less than 0.005) and in those with essential hypertension (0.32 +/- 0.08, n = 24, P less than 0.001) (all data mean +/- SD). Thus our results with hypertensive patients support the findings of other investigators. However, oral contraceptives and drug-induced hypokalaemia greatly modify this system, indicating a regulation of the Na+-Li+ countertransport by hormones. Thus the transport rate does not seem to be an appropriate test for the diagnosis of essential hypertension.     

Abnormal thiol group modulation of sodium-lithium countertransport and membrane fluidity is associated with a disturbed relationship between serum triacylglycerols and membrane function in type II diabetes

In essential hypertension and diabetic nephropathy, sodium-lithium countertransport (Na-Li CT) is an inherited marker, subject to metabolic influences, of cardiovascular risk. Studies in Type II diabetes, taking clinical phenotypes as their starting point, are conflicting. We sought to identify Na-Li CT kinetic abnormalities in Type II diabetes, and only subsequently to seek relationships with clinical variables. Na-Li CT kinetics, membrane fluidity and their modulation by thiol proteins were measured in erythrocytes from 38 patients with Type II diabetes and in 16 normal control subjects. In untreated erythrocytes, Na-Li CT kinetics were similar. Thiol protein alkylation with N-ethylmaleimide generally caused both V(max) and K(m) to fall, but caused K(m) to rise in erythrocytes from 13 out of 38 diabetic subjects, whose native K(m) was low (P=0. 0013 compared with control). V(max) and serum triacylglycerol levels were related in normal controls (r(s)=0.54, P=0.038) and in diabetic subjects whose K(m) fell after N-ethylmaleimide (n=25, r(s)=0.62, P=0.001). Where the K(m) rose after N-ethylmaleimide, V(max) and triacylglycerol levels were not related (n=13, r(s)=-0.39, P=0.183) and membrane fluidity did not increase after N-ethylmaleimide. However, these subgroups were indistinguishable in terms of blood pressure, albuminuria, glycaemia or lipid profiles. Thus abnormalities in the regulation of Na-Li CT and membrane fluidity by key thiol proteins, resembling those seen in essential hypertension and diabetic nephropathy, were apparent in one-third of subjects with Type II diabetes. Membrane abnormalities may indicate a common pathological mechanism. The prognostic significance of Na-Li CT kinetic abnormalities in Type II diabetes must now be confirmed.     

Effects of 1-sarcosine-8-isoleucine-angiotensin II on blood pressure and plasma renin activity in various types of hypertension.

The pharmacological effects of 1-Sar-8-Ile-angiotensin II on blood pressure and plasma renin activity (PRA) were studied in 5 normal subjects and in 19 patients with hypertension of various etiologics including malignant hypertension, renovascular hypertension, essential hypertension, and primary aldosteronism. Intravenous administration of this peptide induced a significant pressor response in normal or low PRA subjects at infusion rates of 100-600 ng/kg/min. Similar pressor response was also observed in renovascular hypertensives with normal PRA who were cured later by surgical treatment. The blood pressure in high PRA group was lowered remarkably by infusion of this angiotensin II inhibitor. A significant increase in PRA was obtained in subjects with malignant hypertension following the infusion of this peptide. However, there was no detectable rise in PRA in other subjects with normal or high PRA. The present data show that circulating angiotensin II plays an important role in maintaining high blood pressure in high PRA patients, especially in malignant hypertension, while it is not directly involved in the maintenance of high blood pressure in human chronic renovascular hypertension.     

Rectal administration of perforated nifedipine capsules in acute severe hypertension in children.

Nine hypertensive children (mean age: 5.0 years (SD: 4.5), range: 10 months to 15 years) were administered nifedipine (capsule) rectally (0.2 to 0.5 mg/kg) when their blood pressures were over 170 mmHg systolic and/or over 110 mmhg diastolic, independent of their ages. The causes of hypertension were acute glomerulonephritis (n = 2), chronic glomerulonephritis (n = 2), renovascular hypertension (n = 4), and polycystic kidney (n = 1). Both systolic and diastolic blood pressures fell in all children after rectal administration of nifedipine, although the response of blood pressure was weak in one child with renovascular hypertension. Blood pressures were lowest at 30 to 60 minutes, and remained under 140 mmHg systolic and 80 mmHg diastolic at least for three hours. Side-effects were headache in one child, palpitations in two children, and facial flushing in three. All of these symptoms were mild, and no special treatment was required. These findings suggest that rectal administration of nifedipine may be effective and the most reliable way to treat young children with severe or urgent hypertension.     

Potential of pulsed Doppler echocardiography in assessing the phasic activity of the left ventricle in patients with symptomatic arterial hypertension

The phasic structure of heart activity was explored in 50 patients suffering from symptomatic arterial hypertensions before and after the operative treatment with the aid of impulse Doppler echocardiography. Of these, 28 patients had renovascular hypertension (RVH), 16 primary aldosteronism (PA), and 6 pheochromocytoma of the adrenals. The data obtained were compared with the polycardiographic readings in patients with essential hypertension (EH). As in the case of EH, the period of left ventricular tension, the phase of asynchronous and isometric contraction, and the phase of isometric relaxation became significantly longer in patients with RVH and PA. In the postoperative period, some phases of heart activity return to normal whereas other phases remained altered throughout the entire observation period, which may be due to the disease standing and irreversibility of myocardial alterations. Therefore, Doppler echocardiography is a sufficiently accurate method of estimating phasic activity of the left ventricle, allowing computation of the period of cardiac cycle phases even in the presence of only one lead of the ECG mounted into an ultrasonic outfit.     

血管压迫延髓腹外侧与原发性高血压相关性研究

目的:评价原发性高血压与延髓腹外侧血管压迫的相关性。方法:2位有经验的影像诊断医师共同分析20例原发性高血压病人、10例继发性高血压病人、18例正常对照组的MRI。结果: 第一组中15例(n=20,75%)、第二组中1例(n=10,10%)、第三组中2例(n=18,11%)延髓头侧腹外侧部(RVLM)受压(P<0.01)。所见责任血管15例原发性高血压小脑后下动脉(PICA)10例(67%),小脑前下动脉(AICA)2例(13%),椎动脉(VA)3例(20%)。另3例为PICA。15例原发性高血压中分别见7例左、右单侧受压,1例两侧同时受压;另3例均为右侧受压。第一组中橄榄后沟中心与最近动脉的距离平均为(1.1±3.0)mm,第二组为(4.9±4.0)mm,第三组为(3.8±2.2)mm(P<0.05)。延髓髓质表面与最近动脉的距离,第一组为(0.5±0.9)mm,第二组为(1.5±1.6)mm,第三组为(1.6±2.1)mm,三组间无显著性差异。结论:原发性高血压与血管压迫RVLM关系密切,而与延髓其它部位受压无关。     

Erythrocyte Na+-Li+ countertransport and blood viscosity in arterial hypertension

The aim of this study was to evaluate together the main hemorheologic parameters and one of the transmembrane ion transport systems in erythrocytes of subjects with normal and elevated blood pressure. Three sex-, age-, and weight-matched groups consisting of 15 normotensive subjects (NT) with no parental hypertension, 15 patients with essential hypertension (EH) at stage 1-II WHO, and eight patients with secondary hypertension (Sec.H), respectively, were studied. Red blood cell Na+-Li+ countertransport (CTT), blood viscosity (eta B) at shear rates of 230 X S-1, 115 X S-1, and 46 S-1 and plasma viscosity (eta P) at shear rate of 46 X S-1 were measured. Plasma proteins and fibrinogen were also evaluated. CTT was higher in EH than in NT (P less than 0.01), while no significant difference was found between NT and Sec. H patients. eta B at 115 X S-1 and 46 X S-1 was higher in EH, but not in Sec. H, than in NT patients (P less than 0.05). No difference in eta P, plasma proteins and fibrinogen levels was observed between EH and NT. Elevated eta B and/or CTT may indicate a structural alteration in the erythrocyte membrane of some essential hypertensive patients. This is consistent with the hypothesis that a widespread membrane disorder is involved in the pathogenesis of primary hypertension.     

The significance of microproteinuria for the diagnosis of kidney involvement in hypertensive disease and secondary forms of arterial hypertension]

N-acetyl-beta-glucosaminidase (NAG) activity, the concentrations of microalbumin (MA) and B2-microglobulin (B2-MG) were measured in urine of 50 healthy subjects and 200 patients suffering from arterial hypertension (AH) with preserved renal function, including patients with essential hypertension (EH), stages I and II, chronic pyelonephritis (CPN), chronic glomerulonephritis (CGN) and vasorenal hypertension (VRH). The healthy subjects, the patients with stage II EH, and those with secondary forms of AH demonstrated significant differences in NAG activity in urine. A positive correlation (r = +0.53; p < 0.03) was discovered between systolic AP and NAG activity in urine of EH patients. The concentration of MA in urine of CGN and VRH patients was significantly higher than that in the healthy subjects, EH and CPN patients. The patients with CPN and VRH showed significantly higher levels of B2-MG in urine.     

Percutaneous angioplasty for renovascular hypertension due to fibromuscular dysplasia.

Because the cause of hypertension is reversible in only 5 percent of patients, extensive initial work-up should only be considered in selected cases. Secondary causes should be suspected in patients whose hypertension begins before age 30 or after age 50 and in patients whose hypertension suddenly worsens after a long period of good control, becomes severe or malignant, or remains refractory to maximal medical therapy. A sudden reduction in renal function in a hypertensive patient and the discovery of a unilateral small kidney may also raise suspicion of a secondary cause. Renovascular disease, one of the most common secondary causes of hypertension, is usually the result of atherosclerosis in older patients and the result of fibromuscular dysplasia in younger patients. Physical examination seldom contributes to the diagnosis. The classic upper abdominal or flank bruit occurs in only 30 to 50 percent of patients with renovascular disease, and is not uncommon in patients with essential hypertension. The gold standard for diagnosis of renovascular disease remains the arteriogram. Transluminal renal angioplasty may be performed during arteriography if a high-grade stenosis is identified. Other management options include medical therapy and surgical revascularization with grafts.     

Outpatient follow-up and management of pregnant women with hypertension

AIM: To study variants of the course of chronic hypertension in pregnant women and determination of factors predisposing to a persistent rise of arterial pressure (AP) in pregnancy. MATERIAL AND METHODS: A total of 50 pregnant women were examined (heart rhythm variability and psychological testing) who had AP 140/90 mm Hg and higher as shown by measurements at three outpatient check-ups. After delivery the patients were retrospectively devided into two groups. Twenty-seven group 1 women had frequent rises of AP to 140/90 and higher throughout pregnancy; twenty-three women of group 2 had high AP only at early terms of pregnancy, later they became normotensive without use of hypotensive drugs. 24-h AP monitoring was made in 29 patients. By its results, two subgroups were identified: 11 patients with essential hypertension and 18 women with neurocirculatory dystonia by hypertensive type. RESULTS: In group 1 there was an early fall of cardiac performance, higher values of SMIP test according to scales 2 (pessimism), 3 (emotional lability), 4 (impetuosity) and 7 (anxiety). CONCLUSION: The analysis of 24-h AP profiles revealed more persistent and significant rise of AP in patients with essential hypertension than in those with neurocirculatory dystonia. They also demonstrated high AP variability correlating with a risk of cardiovascular diseases.     

Increased erythrocyte sodium-lithium countertransport activity in essential hypertension is due to an increased affinity for extracellular sodium

1. Sodium-lithium countertransport activity in a standard assay, its sodium affinity constant and maximum velocity were measured in erythrocytes from normal subjects and from essential hypertensive patients with and without a family history of hypertension. 2. In normal subjects the sodium concentration used in the standard assay was similar to the sodium affinity constant so that the activity measured in this assay was less than the maximum velocity. 3. In patients with essential hypertension and a positive family history, 33% had a sodium-lithium countertransport activity greater than the upper limit of the normal control range (0.4 mmol of Li+ h-1 l-1 of cells). 4. The reason for the raised sodium-lithium countertransport activity was an increased sodium affinity (lower sodium affinity constant) at the outside ion-binding site. 5. Of the patients with essential hypertension and a positive family history but sodium-lithium countertransport activity within the normal range in the standard assay, 30% also had a low sodium affinity constant. 6. A low sodium affinity constant at the outside site of the sodium-lithium countertransporter may be a more specific indicator for a group of patients with inherited hypertension than the standard sodium-lithium countertransport activity assay.     

Management of difficult-to-control hypertension

Hypertension is a primary risk factor for heart disease and stroke, the first and third most common causes of death in the United States. The National Health and Nutrition Examination Survey (NHANES) revealed an increase in awareness of hypertension from 51% to 73%, and, among persons with hypertension, the treatment rate has increased from 31% to 55% (from 1976-1980 vs 1988-1991). Of importance, the rate of those achieving goal blood pressure (< 140/90 mm Hg) has only improved from 10% in NHANES-II (1976-1980) to 29% in NHANES-III (1988-1991). Thus, more than 70% of persons with hypertension in whom good blood pressure control has not been achieved are termed "difficult hypertensives." Failure to achieve treatment blood pressure goals of less than 140/90 mm Hg is usually attributed to the presence of resistant hypertension, a resistant physician, secondary causes of hypertension such as renovascular disease, medication adverse effects, or a nonadherent patient. A practical understanding of the pathophysiology of resistant hypertension, appropriate screening techniques for secondary forms of hypertension, and alternative management strategies for a chronic disease such as hypertension can result in treatment goals being achieved in most difficult hypertensives.     

Short-term blood pressure variability in renovascular hypertension and in severe and mild essential hypertension

This study was designed to examine short-term blood pressure variability (BPV) in patients with different severity and forms of chronic medically treated hypertension. Power spectral analysis of BPV was performed from continuous finger blood pressure (Finapres) recordings. Ten patients with renovascular hypertension (RVHT), 34 with severe essential hypertension (SEHT) and 29 with mild essential hypertension (MEHT) as well as healthy age- and sex-matched control subjects were studied. The RVHT group was characterized by reduced low frequency (LF) power of both systolic and diastolic BPV (P =0.004 and P =0.003 respectively) when compared with the control group. There was also a tendency to lower total power of diastolic BPV (P =0.094). On the contrary, the SEHT group had increased total power of diastolic BPV (P =0.044). However, in the SEHT group, we found no differences in the LF and high frequency power of systolic and diastolic BPV when compared with controls. The MEHT group presented with lower LF power of systolic and diastolic BPV (P =0.028 and P =0.003 respectively) and, in addition, high frequency power of diastolic BPV was lower than in the control group (P =0.020). When the hypertensive groups were compared with each other, total power and LF power of diastolic BPV (P =0.043 and P =0.039 respectively) were lower in the RVHT group than in the SEHT group. In addition, total power of diastolic BPV was lower (P =0.030) in the MEHT group than in the SEHT group. No differences were observed in BPV between the RVHT and MEHT groups. The results show that BPV in hypertensive patients groups behaved differently. This suggests that both the aetiology and severity of hypertension have a significant influence on short-term BPV measured in laboratory conditions and that different control mechanisms are operating in these clinically distinctly different hypertension groups.