[Energy-dependent pathogenesis in chronic hypertension].

The review compiled mainly from the works of the author's laboratory continues to develop a new area in arterial hypertension studies. The author considers the major manifestation of the pathology, i. e.

[Mitochondrial energy conversion disturbance with decrease in ATP production as a source of systemic arterial hypertension].

This review deals with the cellular mechanisms underlying decreased energy status documented in different tissues from experimental rat models of primary and secondary hypertension as well as the involvement of these abnormalities in the pathogenesis of the disease. Such analyses allow us to hypothesize that dysfunction of mitochondrial energy conversion, caused by distinct stimuli, including generalized disturbances of intracellular Ca2+ handling and mitochondria calcium overload found in primary hypertension, leads to uncoupling of oxidation and phosphorylation and attenuated ATP synthesis. Examples of arterial hypertension accompanied by mitochondrial uncoupling and cell ATP depletion (hyperthyroidism, cold hypertension, cyclosporine A intake, etc.

[Insufficient ATP production due to mitochondrial calcium overload as a source of blood pressure elevation in primary hypertension].

The author develops previously expressed hypothesis of causative relationship between primary hypertension and altered mitochondrial energy production, reduced ATP synthesis and tissue energy deficit. These deviations in energy metabolism originate on the basis of generalized alteration of membrane regulation of intracellular Ca(2+) distribution leading to mitochondrial calcium overload and lowering of ATP synthesis. Critical factor determining mitochondrial calcium overload is the development of functional insufficiency of mPT pores of inner mitochondrial membrane facilitate Ca(2+) outflow from matrix of organelles.

[Calcium induced calcium release from liver mitochondria of spontaneously hypertensive rats].

Background: Disturbances of ionic homeostasis of cells and recently discovered cellular energy deficiency due to reduced ATP-synthesizing ability of mitochondria are the most important components of pathogenesis of primary hypertension. Therefore it is essential to elucidate relationship between functioning of ionic transport systems especially that of calcium transport and ATP-synthesizing ability of mitochondria.

Aim: To study calcium induced calcium release from liver mitochondria of spontaneously hypertensive rats at various initial calcium concentrations in medium.

[Decreased ATP-synthesis ability of brain mitochondria in spontaneously hypertensive rats].

Unlabelled: It has been shown previously that a decrease of ATP amount and changed balance of other macroergic phosphates occurs in different tissues of spontaneously hypertensive rats (SHR) compared with control normotensive rats (WKY).

Aim: To assess the ability of SHR brain isolated mitochondria to synthesize ATP and to elucidate its relation to extramitochondrial calcium concentration.

Results: The present work shows for the first time that SHR brain mitochondria initially differ from WKY ones by decreased (by 30%) ATP synthesis rate.

[On the role of insufficient mitochondrial energy production in primary hypertension: the neurogenic constitutive of the pathogenesis].

There are accumulated evidences on existence of an imbalance between energy production and consumption in tissues in primary hypertension resulting in insufficient compensation of energy and its deficiency in cells (human essential hypertension, spontaneous hypertension in rats, SHR). An origin of these abnormalities resides in an alteration of cell mitochondrion ATP-synthetic function which ground is calcium overload of mitochondria due to increased cytosolic calcium redundantly entering into mitochondria and development of insufficiency of mPT pore removing calcium from matrix of the organells. There is an energy production deficiency in brain tissue of individuals with primary hypertension that is not initially caused by alteration of cerebral blood circulation of ischemic type.

[Decreased ATP-synthesis ability of liver mitochondria in spontaneously hypertensive rats (SHR): role of calcium overload of the mitochondria].

It has been shown previously, that a decrease of ATP amount and changed balance of the other macroergic phosphates are observed in different tissues of spontaneously hypertensive rats (SHR) compared with the normotensive controls (WKY). The aim of the present study was to assess the ability of SHR liver isolated mitochondria to synthesize ATP and to clarify its dependence on extramitochondrial calcium concentration. Macroergic phosphate concentrations were measured by high performance liquid chromatography (HPLC).

[The role of mitochondrial calcium overload and energy deficiency in pathogenesis of arterial hypertension].

The author proceeds that increased arterial blood (BP) pressure, reflecting the shift of the threshold blood pressure controlling system, is conditioned by underlying energy deficiency at the cellular level, caused by a decrease of the mitochondrial energy generating function. Elevation of systemic BP in hyperthyroidism resultant from oxidation-phosphorylation uncoupling, leading to decrease of ATP production by mitochondria, is an example of energy dependence of the hypertension phenomenon. In primary hypertension (essential hypertension in humans and spontaneous hypertension in rats) one can speak about genetically determined characteristics of cell membranes (so-called membrane defect) leading to insufficient regulation of intracellular calcium and increased concentrations of free calcium in the cytosol under physiological actions on cell calcium homeostasis mechanisms.

[The role of genome repetitive sequences in primary hypertension].

Genetic determining factors of essential hypertension seems to involve a dynamic mutation or a similar process. The mobile elements of the genome: moderately recurrent sequences, play a special role in initiation of such a process. A possible molecular mechanism of the initiation and development of the dynamic mutation, is described.

Enhanced erythrocyte Na+/H+ exchange predicts diabetic nephropathy in patients with IDDM.

Diabetic nephropathy develops in a subset of patients with an apparently hereditary predisposition. Microalbuminuria and elevated arterial pressure have been proposed as predictors of nephropathy but both appear when renal damage is impending. Enhanced sodium-hydrogen exchange in the cell membranes of diabetic patients is an early marker of diabetic nephropathy but its predictive value has not been assessed.

[Age-related changes in the autonomic ganglia].

Ultrastructure of vegetative ganglions (neck-thoracic, intracardial and intestinal) of Wistar and SHR rats, 26-28 months of age was studied electron-microscopically. The most pronounced changes were found in the neck-thoracic ganglions where, apart from lipofuscin deposits, lamellar bodies were frequently found. Redistribution of neuromediators in the neuron body and an increase of the neuroactive substances release into the intercellular space of the ganglion occur with age.

Amiloride-sensitive Na+/H+ exchange in erythrocytes of patients with NIDDM: a prospective study.

Intensive treatment of non-insulin-dependent diabetes mellitus (NIDDM) decreases the rate of microvascular complications, but is associated with increased incidence of cardiovascular morbidity. Enhanced permeability of plasma membranes for sodium (e.g.

Spironolactone prevents Na+/H+ exchange enhancement in primary aldosteronism.

The study was undertaken to determine the possible effect of an aldosterone antagonist, spironolactone (SP), on red blood cell sodium-hydrogen exchange (NHE) enhancement in primary aldosteronism (PA) and essential hypertension (EH). NHE was measured as the amiloride-inhibited fraction of H+ efflux (V max) from erythrocytes (pHi 6.40 +/- 0.

Increased Na(+)-H+ exchange in red blood cells of patients with primary aldosteronism.

We measured Na(+)-H+ exchange as the amiloride-inhibited fraction of H+ efflux from red blood cells into a sodium-containing medium (pHo 7.95 to 8.05) at pHi values of 6.

[Varying expression of atherosclerosis in the aortic regions with high and low density of the adrenergic nervous plexuses].

The study was made of early autopsies of 20-55-year-old victims deceased because of trauma. Incubation of sections in 2% glyoxylic acid and luminescent microscopy were used. The density of the adrenergic fibers in the central aortic zones which are most frequently affected with atherosclerosis was 2.

Red cell Na+/H+ exchange and B cell alloantigen 883 (D8/17) in patients with acute rheumatic fever and inactive rheumatic heart disease.

The association of Na+/H+ antiport with 883 alloantigen was studied in patients with rheumatic disease. Simultaneous measurements were made of red cell Na+/H+ exchange and 883 alloantigen in microlymphocytotoxic test with D8/17 monoclonal antibodies in 20 patients with acute rheumatic fever, 20 patients with inactive rheumatic heart disease, 20 patients with atherosclerotic heart disease (stable anginal syndrome), and 20 healthy subjects. The number of 883(+) B cells and the Na+/H+ antiport activity were increased in rheumatic fever compared to healthy controls: 24.

[Primary hypertension--cellular resetting and kidney shifting].

Developing the idea of the membrane origin of primary hypertension, we proceed from the following: this form of hypertension is based on widespread (i.e., not limited to one type of cells) abnormalities in the ion transport function of the plasma membrane and its structure, leading to changes in the values of several constraints regulated by the plasma membrane (in particular, pHi, Cai2+); plasma membrane alterations apparently have a genomic source and are initiated by a factor whose impact is mediated by the protooncogenes of the genome: the specific functions of the cell are preserved in these conditions by means of a mechanism of cell adaptation, revealed in the example of adipose tissue and called "cell resetting"; the development of cell resetting simultaneously initiates changes in hormone-target relations which manifest themselves, in particular, in augmented corticosteroid secretion (adrenal cortex hypertrophy), in increased activity of the sympathetic nervous system, and in the phenomenon of hyperinsulinemia; considering membrane alterations as the source of primary hypertension, the author proceeds from the assumption of the role of the blood circulation system as an "intermediate link" between two basic systems (effectors) of water-salt homeostasis at the cellular level and at the level of the whole body, i.

[Effects of La3+ on calcium binding to erythrocyte cytoskeleton].

When the whole erythrocytes were exposed to LaCl3, A--23187, ionomycin, orthovanadate and saponin, there was Ca2+ binding only following La3+ treatment of the cells. The binding was evident at a wide range (0.1 microM--1.

[Calcium binding to the erythrocyte cytoskeleton in spontaneously hypertensive rats].

The paper outlines a new La(3+)-induced mechanism of Ca2+ binding to rat red blood cells. Other compounds elevating intracellular Ca2+ concentrations, such as A-23187, ionomycin, and orthovanadate, and some activators of phosphotransferases (TPA, dibutyryl cAMP) fail to initiate the binding. Inhibitors of calmodulin-dependent processes, such as calmidazolium and trifluoroperazine, diminish La-dependent Ca2+ binding.

[Diagnostic value of the endomyocardial biopsy in the cardiologic therapeutic clinic].

Literature and authors' own data on the diagnostic value of endomyocardial biopsy in cases with clinical diagnosis of dilatation cardiomyopathy are analysed. It is shown that due to this biopsy the diagnosis of more than 20 heart diseases becomes possible. Myocarditis, the diagnosis of which is particularly difficult, is most frequently masked under dilatation cardiomyopathy.

[Differences in metabolic rate of Na+/H+ in the erythrocyte membrane in hypertension and symptomatic hypertension of renal origin].

Na+/H+ turnover rate in the erythrocyte membranes were measured in 20 patients with Stages II and III essential hypertension, 11 patients with renal hypertension and 10 healthy subjects. The patients with essential hypertension showed a two-fold increase in Na+/H+ turnover rate as compared to the controls. Those with renal hypertension displayed no changes in the rate.

[C-src locus determines increased rate of Na+,K+-cotransport and increased calcium content in erythrocytes of (SHR x WKY) F2 hybrids].

26 male F2 hybrids between spontaneously hypertensive (SHR) and normotensive control (WKY) rats (SHRxWKY)F2 were segregated according to their c-src genotype into SS and WW homozygous groups, corresponding to SHR or WKY and WS heterozygous group. Na, K cotransport in erythrocytes in the WW group was equal to that of WKY and differs significantly from that of WS and SS groups (the rate of Na, K cotransport in latter groups was close to that of SHR). Ca content of RBC in WW group was equal to that of WKY, lower than that of WS and SS groups which in turn was significantly lower than in SHR, indicating polygenic control of the trait.

Na+-H+ exchange and other ion-transport systems in erythrocytes of essential hypertensives and spontaneously hypertensive rats: a comparative analysis.

The activity of ion-transport systems and Ca2+-induced erythrocyte haemolysis were compared between patients with essential hypertension and two strains of spontaneously hypertensive rats. Previous data on the increased rate of Na+-Li+ countertransport in erythrocytes of essential hypertensives were confirmed in this study. However, identification of Na+-Li+ countertransport in rat erythrocytes remained a complicated person because of the high rate of sodium-independent efflux of Li+.