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Biomedical subjects

J Zicha

Publications and source records attributed to J Zicha.

At least 91 records · Page 5Linked to original sources
PubMed1992

Platelet aggregation in spontaneous hypertension: genetic determination and correlation analysis.

OBJECTIVE: Hyper-responsive platelets are often found in essential hypertension. It has also been suggested that in hypertensive patients platelets may serve as an easily accessible indicator of abnormalities in contractile cell function. To test these suggestions, we analysed the relationship between platelet aggregation and genetic hypertension in the rat. METHODS: Linear regression analysis of mean values of recombinant inbred strains was used to evaluate the relationship between blood pressure and ADP-induced platelet aggregation. RESULTS: ADP-induced platelet aggregation in platelet-rich plasma in spontaneously hypertensive rats (SHR) was significantly decreased compared with in normotensive Brown Norway (BN) rats. However, in recombinant inbred strains, derived from (SHR x BN) F2 hybrids, correlation analysis revealed that platelet aggregation and blood pressure are independent traits. CONCLUSIONS: The present results suggest strongly that spontaneous hypertension and platelet hypo-aggregability in SHR were linked together by chance due to drift during selective inbreeding. The absence of a correlation between the two traits also indicates that alterations in platelet function in essential hypertension, often found in population-based studies, may have to be reaffirmed in genetically better-defined situations, e.g. by pedigree analysis.

Animals↗
PubMed1992

The influence of high salt intake and/or chronic blood volume expansion on renin-angiotensin system in Brattleboro rats.

The influence of chronic saline drinking and/or DOCA-salt treatment on plasma renin activity and renal renin concentration was studied in vasopressin-deficient homozygous (DI) Brattleboro rats and their vasopressin-secreting heterozygous (non-DI) littermates. The activity of renin-angiotensin system (RAS) can be suppressed even in the absence of vasopressin under the conditions of a sufficiently high salt intake that is achieved in DI rats by consumption of 0.6% saline instead of water. An almost complete RAS suppression in both plasma and kidney was observed in young animals in which high salt intake induced not only blood volume expansion but also blood pressure elevation, i.e. in mildly hypertensive unilaterally nephrectomized saline drinking DI rats as well as in moderately hypertensive DOCA-salt treated DI rats and in non-DI rats with a severe DOCA-salt hypertension. Our results indicate that intravascular expansion and blood pressure changes are important factors for the modulation of plasma and renal renin activity even in the absence of vasopressin.

Animals↗
PubMed1992

Association of red blood cell sodium leak with blood pressure in recombinant inbred strains.

Red blood cell Na+ content as well as ouabain-resistant Na+ and Rb+ (K+) transport (susceptible or resistant to inhibition by loop diuretics) were determined in spontaneously hypertensive rats (SHR) and normotensive Brown Norway (BN) rats the erythrocytes of which were incubated in either saline or Mg(2+)-sucrose medium. Elevated ouabain-resistant Na+ net uptake contrasted with slightly decreased red blood cell Na+ content in SHR compared with BN rats. Acceleration of furosemide- and bumetanide-sensitive Na+ fluxes contributed to enhanced ouabain-resistant Na+ influx into SHR erythrocytes in saline medium, whereas higher furosemide- or bumetanide-resistant Na+ efflux caused greater ouabain-resistant Na+ efflux in Mg(2+)-sucrose medium. Furosemide- and bumetanide-resistant Rb+ leaks were augmented in SHR erythrocytes. The association of the disclosed ion transport alterations with blood pressure was examined in 20 recombinant inbred strains derived from F2 SHR x BN hybrids. Ouabain-resistant Na+ uptake as well as furosemide- and bumetanide-resistant Na+ inward leaks (but not red blood cell Na+ content or furosemide- and bumetanide-sensitive Na+ net uptake) cosegregated with systolic and pulse pressures but not diastolic pressure of the recombinant inbred strains. In contrast, neither ouabain-resistant Na+ efflux nor any component of ouabain-resistant Rb+ uptake correlated positively with blood pressure of the recombinant inbred strains. Increased ouabain-resistant Na+ influx was compensated for by accelerated ouabain-sensitive Na+ extrusion because red blood cell Na+ content was not elevated in the hypertensive strains. Thus, high cell Na+ turnover rates might be related to genetic hypertension if an altered Na+ inward leak would be less effectively compensated for in tissues involved in cardiovascular regulation.

Analysis of Variance↗
PubMed1991

Adrenergic innervation of blood vessels in Dahl rats with salt hypertension.

The adrenergic innervation of major arteries and veins was examined in Dahl salt-sensitive (DS) and salt-resistant (DR) rats using a histochemical fluorescent technique to detect the intraneuronal catecholamine content. Under the conditions of low salt intake the density of adrenergic plexus tended to be higher in DR than in DS rats. A decrease of catecholamine content with a subsequent reduction in the density of visible adrenergic plexus was observed in mesenteric and renal but not in femoral vascular beds of salt hypertensive DS rats. The adrenergic innervation was more altered in veins than in respective arteries. Pronounced alterations of vascular sympathetic innervation induced by high salt intake in DS rats contrasted with negligible changes occurring in DR animals. Observed changes of adrenergic innervation in particular vascular beds of salt hypertensive DS rats could reflect the enhanced catecholamine turnover and sympathetic hyperactivity which is important for the pathogenesis and/or maintenance of salt hypertension in Dahl salt-sensitive rats.

Adrenergic Fibers↗
PubMed1991

Ion transport systems in erythrocyte membrane of spontaneously hypertensive rats (SHR) as compared with normotensive rats of the Brown Norway (BN.lx) strain.

The activity of Na+, K(+)-ATPase in SHR erythrocytes treated with saponin is increased by 30-40% as compared to the Brown Norway (BN.lx) strain whereas the activity of Ca(2+)-ATPase is decreased by 20-30%. Passive permeability of SHR erythrocytes determined by 86Rb influx is increased by 20-30%. In the presence of orthovanadate erythrocytes of SHR accumulate 45Ca by 80% more than BN.lx red cells. There was no difference in Na+/H+ exchange between erythrocytes of SHR and BN.lx animals.

Animals↗
PubMed1991

Cation transport and adenosine triphosphatase activity in rat erythrocytes: a comparison of spontaneously hypertensive rats with the normotensive Brown-Norway strain.

The activity of transport adenosine triphosphatases (ATPases) in saponin-treated erythrocytes as well as the passive membrane permeability for 86Rb+ (K+), 45Ca2+ uptake (in the presence of orthovanadate) and the rate of Na(+)-H+ exchange in intact erythrocytes were studied in spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) and Brown-Norway (BN.lx) rats. Higher Na+,K(+)-ATPase activity, lower Ca(2+)-ATPase activity, increased passive K+ permeability and greater 45Ca2+ uptake were observed in erythrocytes from SHR compared with BN.lx rats. Similar differences in the last two parameters were also disclosed by a comparison of SHR and WKY rats. The rate of Na(+)-H+ exchange in SHR erythrocytes was greater than in WKY rats but equal to that of BN.lx rats. A genetic analysis did not reveal a significant correlation between Na(+)-H+ exchange rate and blood pressure in F2 SHR x WKY hybrids.

Adenosine Triphosphatases↗
PubMed1991

The lack of cardiac hypertrophy in newborn Prague hypertensive rats.

Newborn rats of four different strains with spontaneous hypertension show heart enlargement mainly due to cardiac hyperplasia. To determine whether this anomaly is common in all genetically hypertensive rats, we have compared newborns of Prague hypertensive rats (PHR) with their respective normotensive controls (PNR). The heart ventricles, kidneys and livers of newborn animals were analyzed for their weight, protein and DNA content. The total heart weight and the heart/body weight ratio were significantly lower in PHR than in PNR. On the other hand, there were no differences in total or relative kidney weight and in total liver weight. The relative protein content was significantly lower in kidney and liver of PHR but there were no differences between hypertensive and normotensive animals in relative DNA content of all organs studied. Our results suggest a possible dissociation of genes which determine organ weights from those responsible for blood pressure determination.

Animals↗
PubMed1990

Effects of a chronic high salt intake on blood pressure and the kinetics of sodium and potassium transport in erythrocytes of young and adult subtotally nephrectomized Sprague-Dawley rats.

Erythrocyte Na+ and K+ transport mediated by the Na(+)-K+ pump, the Na+,K+ cotransport system and cation leaks, together with blood pressure, were determined in young and adult rats subjected to either chronic salt deprivation or chronic salt loading combined with subtotal nephrectomy. The kinetics of ion transport were studied in Na+ media as a function of extracellular K+, replaced by extracellular Rb+, and intracellular Na+ varied around the physiological range. A high salt intake increased blood pressure in young but not in adult subtotally nephrectomized rats. Erythrocyte Na+ or K+ contents of salt-deprived and salt-loaded rats did not differ. There were no major changes in Na+,K+ cotransport or cation leaks in salt-loaded rats. Chronic salt loading caused some alterations in the kinetics of the Na(+)-K+ pump, which were greater in young than in adult rats. The most pronounced change was a decreased affinity of the Na(+)-K+ pump for intracellular Na+, which was partially balanced by an increased maximal velocity. At physiological (in vivo) ion concentrations these kinetic alterations caused a slight reduction in total ouabain-sensitive Rb+ uptake [partly due to a decrease in intracellular K+:extracellular Rb+ (1:1) exchange] but no changes in Na+ net extrusion in salt-loaded rats. The erythrocyte Na+ and K+ transport systems showed no changes in intrinsic properties that would favour the development or maintenance of salt hypertension in young over adult rats if similar alterations occurred in tissues relevant for blood pressure control.

Age Factors↗
PubMed1990

Genetic determination of heart and kidney weights studied using a set of recombinant inbred strains: the relationship to blood pressure.

The effects of genetic factors and blood pressure levels on heart and kidney weights were estimated in a set of recombinant inbred (RI) strains obtained by crossing normotensive rat (BN.lx) and genetically hypertensive rat (SHR) progenitor strains. Renal or cardiac hypertrophy in several normotensive RI strains, together with low organ weights in some hypertensive strains, indicate that genetic factors play an important role in heart and kidney weight determination. In RI strains, there was a slight positive correlation between systolic blood pressure and relative heart weight, while relative kidney weight correlated negatively with blood pressure. Indeed, the analysis of the degree of genetic determination in RI strains revealed higher values for the relative kidney weight than for the relative heart weight. Blood pressure has a lower degree of genetic determination than both organs. Several polymorphic loci were found to be associated with organ weight determination. Thus, the analysis of organ weights in RI strains revealed the influence of primary genetic factors rather than secondary blood pressure effects.

Analysis of Variance↗
PubMed1990

Kinetics of Na+ and K+ transport in red blood cells of Dahl rats. Effects of age and salt.

Blood pressure response to chronic high salt intake and kinetics of red blood cell Na+ and K+ (Rb+) transport were studied in salt-sensitive (DS) and salt-resistant (DR) Dahl rats fed a high salt diet (8% NaCl) for 7 weeks from the fifth (young), 12th (adult), or 23rd (old) week of age. The kinetics of ouabain-sensitive Rb+ uptake and Na+ extrusion were determined in Na+ media as a function of both intracellular Na+ (Na+i, 2-8 mmol/l cells) and extracellular Rb+ (Rb+o). In addition, the kinetics of furosemide-sensitive Rb+ uptake (related to Rb+o) and the magnitude of the Na+ and Rb+ leaks were assessed. High salt induced hypertension in young and adult but not in old DS rats although red blood cell Na+ was slightly increased in all age groups of DS rats fed a high salt diet. The kinetic parameters of the Na(+)-K+ pump were similar in DS and DR rats fed a low salt diet. Ouabain-sensitive transport rates were not suppressed in erythrocytes of salt hypertensive Dahl rats. Maximal velocities of the Na(+)-K+ pump (related to Na+i) decreased significantly with age in all groups except in DS rats fed a high salt diet. This was compensated by an age-dependent increase in the affinity for Na+i so that no substantial differences in transport rates between young and old rats were seen at physiological cell Na+ and plasma K+ levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1990

Kinetics of red cell Na+ and K+ transport in Prague hypertensive rats.

Kinetics of ouabain-sensitive, furosemide-sensitive (FS), bumetanide-sensitive (BS) and -resistant Na+ and K+ transport were studied in erythrocytes of Prague hypertensive rats (PHR) and Prague normotensive rats (PNR). Maximal transport rates (Vmax) and apparent affinities for either intracellular Na+ or extracellular K+ (replaced by Rb+) were determined in red cells in which Na+ content varied around the physiological range and that were incubated in Na+ media. No major differences between PHR and PNR were disclosed in the kinetics of ion transport mediated by the Na(+)-K+ pump or BS inward Na(+)-K+ cotransport. FS Rb+ uptake was higher (due to a greater Vmax) in red cells of PHR as compared to PNR. In cells with a lowered Na+ content this elevation of FS Rb+ uptake was largely due to an augmented K(+)-Cl- cotransport which exhibits a low affinity for Rb+o and is blocked by 1 mM furosemide but not by 10 microM bumetanide. Red cells of PHR and PNR strains did not differ in either Na+ or Rb+ leaks. A slight increase of red cell Na+ content in PHR was evaluated in terms of the pump-leak concept. The present study did not reveal any obvious kinetic abnormalities of red cell cation transport the presence of which in tissues involved in blood pressure regulation would favor the development or the maintenance of genetic hypertension in PHR.

Animals↗
PubMed1990

Reversibility and partial reactions of the Na(+)-K+ pump of rat erythrocytes.

An assay was developed to characterize the kinetic parameters of the Na(+)-K+ pump of rat erythrocytes under conditions as physiological as possible. Changes in the red cell Na+ and Rb+ content were determined in Na+ media (containing 2.5 mM inorganic phosphate (PO4) as a function of cell Na+ (2-8 mmol/l) and extracellular Rb+ (0.2-5 mM). Evaluation of the data revealed that under these conditions the Na(+)-K+ pump mediates, in addition to forward running 3 Nai+: 2 Rbo+ exchange, 1 Ki+:Rbo+ exchange and pump reversal (3 Nao+:2 Ki+ exchange). The two latter modes of Na(+)-K+ pump operation are accelerated by PO4 and lowering of cell Na+. At physiological cation and PO4 concentrations, 1Ki+:Rbo+ exchange contributes by 30-60% to total ouabain-sensitive Rb+ uptake. Thereby, the stoichiometry of ouabain-sensitive Na+ net-extrusion to Rb+ uptake is reduced to values between 1.0 and 0.5. Only at cell Na+ contents above 20 mmol/l the Na+:Rb+ stoichiometry approaches the value of 3:2 = 1.5. At certain constellations of Nai+ and Rbo+ the Na(+)-K+ pump cannot perform any net-transport of Na+ and K+ (Rb+). These equilibrium points are not far from those expected from thermodynamic considerations. The results demonstrate that in normal rat erythrocytes the reversible reaction cycle of the Na(+)-K+ pump runs in several modes of operation. The "abnormal" modes complicate the interpretation of unidirectional fluxes mediated by the Na(+)-K+ pump.

Animals↗
PubMed1990

Influence of chronic alterations of salt intake and aging on the kinetic of red cell Na+ and K+ transport in Sprague-Dawley rats.

The kinetics of Na+ and K+ (Rb)+ transport mediated by the Na(+)-K+ pump and Na(+)-K+ cotransport system (assessed as a function of Rb+o and Na+i) as well as the magnitude of cation leaks were determined in red cells of young male rats subjected to chronic salt deprivation or salt loading (0.1% and 8% NaCl diet). These salt intake alterations induced moderate kinetic changes of the Na(+)-K+ pump which did not result in significant changes of ouabain-sensitive (OS) Rb+ uptake or Na+ net extrusion at in vivo Na+i and K+o concentrations because a decreased affinity for Na+i in salt-loaded animals was compensated by an increased maximal transport rate. High furosemide-sensitive (FS) Rb+ uptake in red cells of salt-deprived rats was caused by an increase of both the maximal transport rate and the affinity for Rb+o. Cation leaks were also higher in salt-deprived than in salt-loaded rats. In three age groups of rats fed a 1% NaCl diet FS Rb+ uptake (but not FS Na+ net uptake) rose with age due to an increasing maximal transport rate whereas the affinity of the cotransport system for Rbo+ did not change. The age-dependent changes in the kinetics of the Na(+)-K+ pump resulted in a slight decrease of OS Rb+ uptake with age that was not paralleled by corresponding Na+ net extrusion. No major age-related changes of cation leaks were found. Thus some intrinsic properties of red cell transport systems can be altered by salt intake and aging.

Aging↗
PubMed1990

Body fluids and their distribution in experimental hypertension.

The relation between blood pressure level and extracellular fluid volume and its distribution was studied in rats subjected to the following hypertensive stimuli--1K1C and 2K1C renal artery constriction, subtotal nephrectomy-salt and DOCA-salt. In all experimental groups the blood pressure increase was accompanied by increased extracellular fluid volume which was not always distributed proportionally between intravascular (PV) and interstitial (IFV) compartments. The blood pressure rise was further potentiated by plasma volume expansion so that the increased PV/IFV ratio was associated with a more pronounced hypertensive response (1K1C vs 2K1C, DOCA-salt vs subtotal nephrectomy-salt). However, adequate expansion of interstitial fluid is a necessary prerequisite for the hypertensive response. In DOCA-salt treated DI Brattleboro rats (lacking antidiuretic vasopressin action) plasma volume expansion per se was not accompanied by severe DOCA-salt hypertension. It is concluded that the expansion of both compartments of extracellular space, i.e. plasma volume and interstitial fluid volume, was necessary for a full development of severe hypertension. The expansion of only one of these compartments was accompanied by a mild blood pressure increase or blood pressure did not change significantly.

Animals↗
PubMed1989

Vasopressin and water distribution in rats with DOCA-salt hypertension.

The role of vasopressin in the regulation of body water volume and its distribution to intravascular, interstitial and intracellular compartments, and the importance of particular body water compartments in the pathogenesis of DOCA-salt hypertension were studied in young Brattleboro rats. Vasopressin-deficient, vasopressin-synthesizing and vasopressin-deficient rats chronically supplemented with deamino-8-D-arginine vasopressin (dDAVP) were compared with water-drinking controls. The chronic DOCA-salt treatment caused a marked hypertension in vasopressin-synthesizing animals; in these animals body water was slightly increased due to the expansion of extra-cellular fluid volume whereas intracellular water tended to decrease, so that the ratio of extracellular fluid volume to intracellular water rose significantly. The development of DOCA-salt hypertension was attenuated in the vasopressin-deficient rats, which had a similar level of total body water, slightly increased intracellular water and significantly decreased extracellular fluid volume compared with the hypertensive vasopressin-synthesizing rats. Consequently, in the vasopressin-deficient rats, the ratio of extracellular fluid volume to intracellular water did not differ from that of controls. A vasopressin deficiency was associated with a failure to expand the interstitial fluid volume although plasma volume was increased. Unaltered total body water together with elevated plasma osmolality indicated an extracellular water deficiency in DOCA-salt-treated vasopressin-deficient rats. Chronic dDAVP supplementation restored the body fluid pattern and the hypertensive response of the DOCA-salt-treated vasopressin-deficient rats. In conclusion, the antidiuretic effects of vasopressin are necessary for the interstitial fluid volume expansion that is essential for a full development of DOCA-salt hypertension.

Animals↗
PubMed1989

Antidiuretic and pressor actions of vasopressin in age-dependent DOCA-salt hypertension.

The role of antidiuretic and pressor effects of vasopressin (VP) in deoxycorticosterone acetate (DOCA)-salt hypertension was studied in young and adult Brattleboro rats. The antidiuretic VP action was a necessary prerequisite for the development of severe DOCA-salt hypertension. The insufficient expansion of extracellular fluid volume in DOCA-salt-treated VP-deficient (DI) rats was associated with the attenuation of their hypertensive response, although they had highly increased blood volume and extracellular sodium. Chronic [deamino]-D-arginine vasopressin supplementation that restored volume and distribution of body fluids in DI rats permitted the full development of DOCA-salt hypertension. Blood pressure response to DOCA-salt treatment was always greater in young than in adult Brattleboro rats (even in animals lacking pressor or both VP effects). In animals in which antidiuretic VP effects were present, the pattern of body fluid response to DOCA-salt treatment was also age dependent. There was a tendency to intravascular expansion in young hypertensive rats, whereas an increase of interstitial fluid volume was found in adult animals. The elimination of VP pressor action lowered systemic resistance much more in adult than in young hypertensive rats. We conclude that 1) in adult but not in young rats antidiuretic VP effects are essential for the occurrence of blood pressure response to DOCA-salt treatment, 2) the restoration of body fluids due to antidiuretic VP action enables the development of hypertension in both age groups of DI rats, and 3) pressor VP effects contribute to the maintenance of hypertension, especially in adult animals.

Aging↗