Biomedical subjects

J Zicha

Publications and source records attributed to J Zicha.

At least 19 recordsLinked to original sources

PubMed1996

Cell calcium handling and intracellular pH regulation in hereditary hypertriglyceridemic rats: reduced platelet response to thrombin stimulation.

Multiple cell membrane alterations have been described in humans and animals with various genetic forms of hypertension and/or dyslipidemia. The aim of our study was to characterize some properties of platelets and/or erythrocytes (cytosolic calcium handling, intracellular pH regulation and thrombin responsiveness) in a new model of genetic hypertension associated with hyperlipidemia-Prague hereditary hypertriglyceridemic (HTG) rats. There were no differences in basal cytosolic Ca2+ values in platelets or erythrocytes of HTG rats and control Wistar rats. Ca2+ influx into erythrocytes was also similar in HTG and control rats. In both strains Ca2+ influx correlated positively with plasma triglycerides. The slope of this relationship was less steep in HTG than in Wistar rats. Cytosolic Ca2+ response to thrombin stimulation was smaller in HTG platelets, which were also characterized by a major reduction of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels. Platelets of HTG rats had the same basal intracellular pHi values and similar buffering capacity as control rats but their pHi response to thrombin stimulation was substantially reduced. It can be concluded that reduced responsiveness to thrombin stimulation is a major alteration found in platelets of hypertensive hereditary hypertriglyceridemic rats.

Animals↗

PubMed1996

Major histocompatibility complex in the rat and blood pressure regulation.

The objective of this study was to evaluate whether the major histocompatibility complex of the rat can be related to blood pressure (BP) level and BP response to stress. Blood pressure was determined under light ether anesthesia or during moderate restraint stress in normotensive Lewis rats, in rat strains congenic with respect to their RT1 haplotype [LEW.1A (RT1a) and LEW.1W (RT1u)], and in their recombinant lines LEW.1AR1 (RT1ar1), LEW.1AR2 (RT1ar2), LEW.1WR1 (RT1wr1), and LEW.1WR2 (RT1wr2). Under light ether anesthesia, systolic blood pressure was similar in Lewis, LEW.1A, and LEW.1W rats. There were also no significant differences in blood pressure in LEW.1AR1 and LEW.1AR2 animals when compared with Lewis or LEW.1A rats. In contrast, BP was significantly increased in LEW.1WR2 rats. On the other hand, moderate restraint stress induced a BP increase in animals of all recombinant lines compared to the respective congenic strains. These results confirmed our previous finding in recombinant inbred strains about the significant role of RT1 complex in BP regulation. Moreover, our data indicated that BP can be influenced by interaction of individual regions of the RT1 complex on the genetic background of Lewis strain.

Anesthesia, Inhalation↗

PubMed1996

Platelet calcium handling is different in rats with salt-dependent and spontaneous forms of genetic hypertension.

Increased platelet cytosolic free calcium concentration ([Ca2+]i) has been demonstrated in both human essential hypertension and spontaneous hypertension of the rat. The present study was designed to extend the investigation on platelet Ca2+ handling to two models of salt-dependent genetic hypertension (Sabra and Dahl rat strains). No major [Ca2+]i elevation was seen in salt hypertensive SBH Sabra or SS/Jr Dahl rats. This contrasts with the data obtained in Lyon hypertensive rats (a spontaneous form of genetic hypertension) in which basal platelet [Ca2+]i was clearly increased and correlated positively with diastolic blood pressure. In these two strains, basal platelet [Ca2+]i correlated with pulse pressure but not with diastolic pressure. The absence of a significant relationship between platelet [Ca2+]i and diastolic pressure in both Sabra and Dahl rats indicates that, at least in young rats with developing salt hypertension, platelet cytosolic calcium need not reflect calcium changes occurring in the vascular smooth muscle or resistance arterioles. In contrast to the high values seen in Lyon hypertensive rats, the [Ca2+]i rise induced by thrombin was unchanged in salt-sensitive SS/Jr Dahl rats and substantially reduced in hypertension-prone SBH rats (irrespective of salt intake). The initial rate of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels was similar in SBN and SBH as well as in SR/Jr and SS/Jr rats kept on a low-salt diet but was reduced by high salt intake in platelets of salt-resistant (SBN and SR/Jr) animals only. Since platelets of Lyon hypertensive rats are also characterized by greater initial rate of thrombin-induced Mn2+ entry, this parameter was always higher in rats with established hypertension compared to their respective normotensive controls. Our study demonstrated that alterations of platelet Ca2+ handling are different in salt-dependent than in spontaneous forms of genetic hypertension.

Animals↗

PubMed1996

[Personal clinical experience in the treatment of arterial hypertension using amlodipine].

In 15 centres of the Czech Republic the antihypertensive effect of Amlodipine-Norvasc of Pfizer Co. was tested in 155 patients with mild or medium severe hypertension. The patients were treated by monotherapy, using doses of 5 mg (92%) and 10 mg (8%) per day. In all investigated hypertensive subjects a statistically significant decline of the systolic and diastolic blood pressure occurred in the course of the 12-week investigation (P smaller than 0.01) without affecting the heart rate. The rate of undesirable effects of treatment was very low: only three patients (1.9%) discontinued treatment on account of undesirable effects. The most frequent ones included perimalleolar oedema, the sensation of fullness, headache, cardiac palpitations, vertigo and insomnia. Evaluation of the antihypertensive effectiveness and tolerance of the preparation by the physician and patient is positive, and Amlodipine-Norvasc of Pfizer Co. holds therefore, because of its pharmacokinetic and pharmacodynamic properties, an important place among calcium channel inhibitors of the second generation.

Adolescent↗

PubMed1996

[The effect of chemical sympathectomy on the adrenergic innervation of the blood vessels belonging to different organs in salt-sensitive and salt-resistant Dahl-strain rats].

The action of chemical desympathization by 6-hydroxydophamine influencing adrenergic innervation in different organs vessels (mesenterial, renal and femoral) was studied using histochemical fluorescent method in salt susceptible and salt-resistant Dahl rats kept on a low- and high-salt diet. Heterogeneity of adrenergic innervation of different region vessels was established to display and 6-hydroxydophamine caused complete desympathization only in mesenterial artery and in all veins, while in renal artery retained adrenergic plexus its certain branching and femoral artery-in two thirds of its surface. The process of reinnervation in vessels running with different intensity in different animals and in different vessels was found to start in vessels of majority of animals on day 5-6 after the chemical desympathization. 6-hydroxydophamine had greater impact on the vessels of salt-susceptible high salt rat (hypertension) and salt-resistant high-salt-diet (normension) rats. Thus, the state of arterial and venous adrenergic apparatus in hypertension Dahl rats is determined not by the increased blood pressure itself but by the natrium metabolism disturbance.

Adrenergic Fibers↗

PubMed1996

Abnormal regulation of cytosolic calcium and pH in platelets of Sabra rats in early phases of salt hypertension development.

Platelet cytosolic free calcium concentration ([Ca2+]i) and pH (pHi) have been reported to be altered in both human essential and rat spontaneous hypertension. The aim of our study was not only to search for the occurrence of such alterations in platelets of rats with salt-induced hypertension but also to investigate whether these changes might precede blood pressure rise in this form of experimental hypertension. Using fluorescent probes fura-2 and BCECF, basal values and thrombin-induced changes of [Ca2+]i and pHi were determined in platelets of young hypertension-prone (SBH) and hypertension-resistant (SBN) Sabra rats fed either low-salt (0.3% NaCl) or high-salt (4% NaCl) diets. Under the conditions of low salt intake, basal [Ca2+]i values were similar in SBH and SBN rats, whereas pHi was significantly lower in SBH than in SBN animals. Thrombin induced smaller [Ca2+]i elevation but greater pHi rise in SBH rats compared with SBN animals. The initial rate of thrombin-induced Mn2+ entry, which reflects the opening of a particular subclass of thrombin-operated Ca2+ channels, was similar in both strains. The moderate hypertension elicited in SBH rats by high salt intake was not associated with major alterations of basal [Ca2+]i or pHi values. High salt diet feeding did not influence [Ca2+]i and pHi responses to thrombin in either strain. In contrast, high salt intake reduced thrombin-induced Mn2+ entry in SBN but not in SBH rats. Basal platelet [Ca2+]i values correlated positively with systolic but not with diastolic blood pressure. This could be ascribed to a very close relationship of basal [Ca2+]i values with pulse pressure. The abnormalities of [Ca2+]i and pHi handling in platelets of Sabra rats with salt-dependent genetic hypertension differ from those described in essential hypertensive patients or rat strains with spontaneous forms of genetic hypertension. Our study also indicated that alterations of platelet [Ca2+]i do not precede blood pressure elevation in salt hypertension.

Animals↗

PubMed1995

Alterations of cytosolic calcium in platelets and erythrocytes of Lyon hypertensive rats.

Platelet cytosolic free calcium concentration ([Ca2+]i) and intracellular pH (pHi) (including their responses to thrombin), as well as erythrocyte [Ca2+]i and 45Ca2+ influx, were studied in Lyon hypertensive (LH) and normotensive (LN) rats aged 3 months. Platelets of LH rats were characterized by substantially elevated basal [Ca2+]i values, higher [Ca2+]i levels after thrombin stimulation, and enhanced initial rate of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels. Basal platelet pHi values were not significantly different in LH and LN animals but thrombin elicited a significant alkalinization only in LH platelets. Erythrocytes of LH rats had an enhanced initial rate of 45Ca2+ and tended to elevated [Ca2+]i levels. Our data indicate profound alterations in cell Ca2+ handling in platelets and erythrocytes of LH rats, similar to those previously described in spontaneously hypertensive rats of the Okamoto-Aoki strain. The analysis of the relations between blood pressure, plasma lipids, and cell Ca2+ handling suggested that triglycerides, but not cholesterol, might be involved in altered platelet Ca2+ handling in LH rats.

Animals↗

PubMed1995

Hereditary hypertriglyceridemic rat: a new animal model of metabolic alterations in hypertension.

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na+ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.

Animals↗

PubMed1995

Body fluid alterations and organ hypertrophy in age-dependent salt hypertension of Dahl rats.

The relationship between possible alterations in the volume or distribution of extracellular fluid and the development of salt hypertension was studied in inbred salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats. Blood pressure, cardiac and renal hypertrophy as well as body fluid volumes were determined in young and adult SS/Jr and SR/Jr rats of both sexes that were subjected to low, normal or high salt intake for various periods of time. Salt hypertension in young salt-sensitive rats fed a 4% NaCl diet was not accompanied by any substantial intravascular or interstitial expansion as compared to salt-resistant rats that remained normotensive. There was no sex difference in the response of blood pressure or body fluids to high salt intake. Major expansion of plasma and blood volume, which was elicited by 8% NaCl diet feeding from prepuberty, was not accompanied by a further blood pressure rise (compared to salt hypertensive SS/Jr rats fed 4% NaCl diet). In conclusions, salt hypertension can occur in Dahl salt-sensitive rats without major salt and water retention. The degree of intravascular expansion is not directly related to blood pressure levels in salt-loaded Dahl rats. A high salt intake seems to exert its hypertensive effects in Dahl rats preferentially by influencing the balance of vasoconstrictor and vasodilator systems rather than by increasing the haemodynamically active intravascular volume.

Aging↗

PubMed1995

High blood pressure of hypertriglyceridaemic rats is related to metabolic disturbances.

A set of 131 F2 hybrids, obtained from a cross between normotensive Lewis and hypertensive hypertriglyceridaemic (HTG) rats, was studied in order to assess the relationship between blood pressure, plasma triglycerides and plasma uric acid. In progenitors, the plasma levels of triglycerides and uric acid were twice as high in HTG rats than in the Lewis rats. It was observed in the F2 cohort that high mean arterial pressure (MAP) was unrelated to body weight and relative heart or kidney weights. On the other hand, there were significant correlations between MAP and plasma triglycerides (r = 0.420, n = 131, p < 0.0001) and between MAP and plasma uric acid (r = 0.325, p < 0.001). Plasma triglycerides of F2 hybrids were below the midparental values, suggesting a stronger influence of normotensive Lewis alleles. In conclusion, hypertension in hypertriglyceridaemic rats strongly cosegregated with plasma triglycerides and plasma uric acid. Our results indicated a linkage between high blood pressure and several metabolic alterations characteristic for the X syndrome.

Animals↗

PubMed1995

Plasma triglycerides cosegregate with erythrocyte sodium content in F2 rats of HTG x Lewis cross.

The possible association of plasma lipids (triglycerides and cholesterol) with erythrocyte Na+ content (Na+i) and/or with alterations in red cell Na+ and K+ (Rb+) transport was studied in a population of F2 hybrids obtained by crossing hypertensive Prague hereditary hypertriglyceridaemic (HTG) rats with normotensive Lewis rats. The obtained data indicated a strong cosegregation (p < 0.001) of plasma triglycerides with erythrocyte Na+ content. This was the cause for the close correlation of plasma triglycerides with the Na(+)-K+ pump activity (measured as ouabain-sensitive Na+ extrusion). On the contrary, there was only marginal association (p < 0.05) of erythrocyte Na+ content with plasma cholesterol which was significantly (p < 0.01) related to burnetanide-sensitive Rb+ uptake mediated by the Na(+)-K+ cotransport system. Na+ leak (bumetanide-resistant net Na+ uptake) correlated positively with blood pressure in female but not in male F2 rats. The close association between plasma triglycerides and erythrocyte Na+ content suggests that ion transport alterations might contribute to mechanisms responsible for the cosegregation of blood pressure with plasma triglycerides in HTG x Lewis F2 hybrids.

Animals↗

PubMed1994

Angiotensin AT1 receptor blockade by specific antibody prevented two-kidney, one-clip renal hypertension in the rat.

The effect of chronic angiotensin AT1 receptor blockade by a specific antibody on the development of two-kidney, one-clip renal hypertension was studied in Wistar rats. Renal artery constriction resulted in a fast and large increase in blood pressure in comparison with that of control rats. On the other hand, the pre-immunization of rats with a small part of the angiotensin AT1 receptor completely prevented the development of renal hypertension. We conclude that the development of two-kidney, one-clip renal hypertension can be blocked by a specific antibody raised against a part of the angiotensin AT1 receptor.

Amino Acid Sequence↗

PubMed1994

Alterations of membrane properties in erythrocytes of salt hypertensive Sabra rats.

This study was designed to investigate the effects of a hypertensive stimulus, high salt intake, in hypertension-prone (SBH) and -resistant (SBN) Sabra rats on erythrocyte Na+ content (Na+i), Ca2+ influx and cytosolic Ca2+ concentration ([Ca2+]i). The relationships of these parameters to plasma lipids, circulating digoxin-like immunoreactivity and membrane microviscosity, determined by the fluorescence anisotropy of trimethylamino-diphenylhexatriene (TMA-DPH) and diphenylhexatriene (DPH), were also evaluated. Erythrocytes of SBH rats were characterized by increased [Ca2+]i, unchanged Ca2+ influx and reduced Na+i. There were no significant differences in the plasma digoxin-like immunoreactivity between the two strains. High-salt intake decreased membrane microviscosity (DPH anisotropy) in SBH rats but did not alter the above parameters. Erythrocyte [Ca2+]i correlated positively with diastolic blood pressure and negatively with erythrocyte Na+i. Membrane dynamics evaluated by the two fluorescent probes did not correlate with [Ca2+]i, Ca2+ influx or Na+i whereas DPH anisotropy was inversely related to blood pressure. These relationships were independent of plasma cholesterol or triglycerides. It can be concluded that 1) similarly to earlier observations in essential hypertension and spontaneously hypertensive rats, erythrocyte [Ca2+]i correlates positively with blood pressure in salt-dependent hypertension, and 2) increased erythrocyte Na+ content need not be a hallmark of hypertension.

Animals↗

PubMed1994

Erythrocyte ion transport alterations in hypertriglyceridaemic rats.

1. Hypertension appears to be associated with both abnormalities in ion transport and disturbances in lipid metabolism. The aim of the present study was to search for alterations in erythrocyte ion transport in hereditary hypertriglyceridaemic rats. This strain is characterized by a pronounced elevation of blood pressure which correlates with the plasma triacylglycerol level. 2. Erythrocyte Na+ content was elevated in hypertriglyceridaemic rats due to an increased ouabain-resistant Na+ net uptake. This was caused not only by the acceleration of bumetanide-sensitive Na+ inward co-transport, but also by the augmentation of bumetanide-resistant Na+ inward leak. A moderate enhancement of bumetanide-sensitive Rb+ uptake was seen in hypertriglyceridaemic animals, but there were no changes in bumetanide-resistant Rb+ leak. 3. The plasma triacylglycerol level correlated positively not only with blood pressure (P < 0.001) but also with ouabain-resistant Na+ transport (P < 0.002), bumetanide-sensitive Na+ and K+ (Rb+) co-transport (P < 0.01 and P < 0.001, respectively), bumetanide-resistant Na+ leak (P < 0.02) and erythrocyte Na+ content (P < 0.05). 3. Thus the association of augmented ouabain-resistant Na+ transport with elevated blood pressure in this form of experimental hypertension might be mediated by genetic disorders of lipid metabolism.

Animals↗

PubMed1994

Platelet membrane microviscosity in Sabra rats with early salt hypertension.

1. To investigate the possibility that arterial hypertension is associated with changes in the physicochemical properties of cell membranes, we have studied the effects of dietary salt loading on platelet membrane microviscosity in hypertension-prone and -resistant Sabra rats. 2. Sixteen hypertension-prone and 14 hypertension-resistant Sabra rats were submitted to either a low-salt (0.25% NaCl) or a high-salt (4% NaCl) diet for 3-4 weeks. Platelet membrane anisotropy was determined, in the presence and absence of extracellular Na+, using two fluorescent probes, diphenylhexatriene and trimethylamino-diphenylhexatriene, inserted in different areas of the cell membranes. 3. A decrease in diphenylhexatriene anisotropy was demonstrated when platelets of hypertension-prone (but not hypertension-resistant) Sabra rats were suspended in a Na(+)-free medium. This alteration in membrane dynamic properties is localized within the hydrophobic core of the platelet membranes and is independent of salt intake. It reflects an abnormal fluidizing effect of extracellular Na+ removal. 4. Platelets of hypertension-prone and hypertension-resistant Sabra rats did not differ significantly in trimethylamino-diphenylhexatriene fluorescence anisotropy, irrespective of the incubation media used. Extracellular Na+ removal caused an increase in trimethylamino-diphenylhexatriene fluorescence anisotropy in all groups, the change being greatest in salt-loaded rats. 5. This study indicates that platelet membrane microviscosity is specifically altered in the hypertension-prone Sabra rat irrespective of salt intake. This raises the question of the relation of this inherited defect with the susceptibility of this strain to dietary salt loading.

Animals↗

PubMed1994

Platelet and erythrocyte membrane microviscosity in Lyon hypertensive rats.

The altered membrane microviscosity demonstrated in various cells of spontaneously hypertensive rats (SHR) and essential hypertensive (EH) patients has been proposed to play an important role in the pathogenesis of genetic forms of hypertension. The aim of this study was to evaluate possible changes of membrane microviscosity in platelets and red cell ghosts of Lyon hypertensive (LH) and normotensive (LN) rats. Both erythrocyte and platelet membranes of LH rats had a clear tendency to reduced DPH fluorescence anisotropy reflecting the decreased core membrane microviscosity. On the other hand, there were no changes in TMA-DPH fluorescence anisotropy that characterizes the dynamic properties of the outer membrane leaflet. DPH, but not TMA-DPH, anisotropy correlated negatively with blood pressure. This was true for both red cell ghosts and platelets. Membrane microviscosity had no significant relationship to plasma cholesterol or triglycerides. In platelets, TMA-DPH anisotropy correlated positively with cytosolic free calcium concentration ([Ca2+]i). A similar trend was observed in erythrocytes. In contrast, DPH anisotropy had an inverse relationship to platelet [Ca2+]i. It can be concluded that the alterations of membrane microviscosity seen in LH rats are completely different from those reported in SHR animals and that surface and core membrane microviscosity differ in their relationship to blood pressure and [Ca2+]i.

Animals↗

PubMed1994

Use of recombinant inbred strains for evaluation of intermediate phenotypes in spontaneous hypertension.

1. The HXB/BXH recombinant inbred (RI) strains, derived from the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway (BN.1x) rat, represent a very useful system for gene mapping and for genetic analysis of certain model diseases, such as spontaneous hypertension. 2. These RI strains were genotyped in multiple genetic polymorphisms and characterized in blood pressure and some intermediate phenotypes. 3. The analysis of RI strains has revealed that (i) a gene in the vicinity of the major histocompatibility complex (RT1) on chromosome 20, a kallikrein-related gene on chromosome 4 and the renin gene on chromosome 13 were significantly associated with blood pressure, and (ii) Na+ leak in red blood cells correlated with blood pressure whereas relative heart and kidney weights as well as platelet aggregation did not.

Animals↗

PubMed1994

Haemodynamic changes induced by short- and long-term sodium chloride or sodium bicarbonate intake in deoxycorticosterone-treated rats.

The contribution of chloride to the haemodynamic changes of salt-dependent deoxycorticosterone (DOC) hypertension was studied in young Wistar rats subjected to dietary loading with sodium chloride (NaCl) or sodium bicarbonate (NaHCO3). Mean arterial pressure (MAP), cardiac output, systemic resistance (TPR) and arterial rigidity (estimated from pulse pressure/stroke volume ratio, PP/SV) were determined in conscious chronically cannulated rats. DOC-induced increase of MAP and TPR appeared earlier in NaCl-loaded than in NaHCO3-loaded rats. After 4-6 weeks of hypertensive treatment MAP, TPR and PP/SV ratio were higher in DOC-treated rats fed NaCl diet than in those fed NaHCO3 diet. In contrast, after a long-term hypertensive regimen (lasting for 7-9 weeks) there was no significant difference in either MAP or TPR between rats loaded with NaCl or NaHCO3. On the other hand, DOC hypertension induced by a long-term feeding of NaHCO3 diet was not associated with an increase of arterial rigidity which was characteristic for DOC-NaCl hypertensive rats. Thus, a sufficiently long selective dietary sodium loading is capable to increase the systemic resistance but not to alter the arterial rigidity. This was also confirmed by a comparison of blood pressure-matched DOC hypertensive rats fed NaCl or NaHCO3 diets. These animals did not differ in the degree of systemic resistance elevation but the arterial rigidity was increased only in NaCl-loaded rats.

Animals↗