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Biomedical subjects

W Zidek

Publications and source records attributed to W Zidek.

At least 181 records · Page 10Linked to original sources
PubMed1994

Effect of inhibition of sarcoplasmic Ca(2+)-ATPase on vasoconstriction and cytosolic Ca2+ in aortic smooth muscle from spontaneously hypertensive and normotensive rats.

To evaluate the influence of the sarcoplasmic Ca(2+)-ATPase, isometric vasoconstrictions of aortic strips from spontaneously hypertensive rats from the Münster strain (SHR) and normotensive Wistar-Kyoto rats (WKY) were measured after inhibition of Ca(2+)-ATPase by thapsigargin. Inhibition of Ca(2+)-ATPase by thapsigargin caused a biphasic contractile response of the aorta in both SHR and WKY (maximum increase of tension: 1.7 +/- 0.3 x 10(-3) Newton and 2.1 +/- 0.3 x 10(-3) Newton, respectively; mean +/- SE). The second peak of the contractile response was abolished in the absence of external calcium or by inhibition of transplasmamembrane calcium influx by nifedipine, indicating that the second peak occurs as a consequence of calcium influx from the extracellular space. The initial peak of the contractile response after thapsigargin administration was abolished in the presence of an intracellular calcium antagonist, 8-(diethylamino-)-octyl-3,4,5-trimethoxybenzoate (TMB-8), indicating that the initial response was due to calcium release from intracellular stores. Measurements using the fluorescent dye fura2 showed that thapsigargin increased the cytosolic free calcium concentration ([Ca2+]i) in SHR by 72.6 +/- 7.3 nmol/l (n = 34) and in WKY by 53.3 +/- 6.6 nmol/l (n = 39), showing no significant differences between the two strains. The inhibition of Ca(2+)-ATPase increases [Ca2+]i and causes vasoconstriction. The vasoconstriction produced by thapsigargin is not significantly different between SHR and WKY.

Animals↗
PubMed1994

Effect of Na,K-ATPase inhibition on cytosolic free calcium ions in vascular smooth muscle cells of spontaneously hypertensive and normotensive rats.

OBJECTIVE: To investigate the role of Na(+)-Ca2+ exchange in the regulation of cytosolic free Ca2+ and the pathogenesis of primary hypertension. METHOD: Cytosolic free Ca2+ ([Ca2+]i) in cultured vascular smooth muscle cells from normotensive and spontaneously hypertensive rats of the Münster strain was measured using the fluorescent dye fura-2 after inhibition of Na+,K+ATPase by ouabain and after addition of angiotensin II. RESULTS: [Ca2+]i showed a rapid increase together with a depolarization of membrane potential as measured by merocyanine 540. The ouabain-induced increase in [Ca2+]i was blocked in Ca(2+)-free medium and by nifedipine, but incubation with the inhibitor of the Na(+)-Ca2+ exchange, NiCl2, did not diminish the effect of ouabain. Likewise, in Na(+)-free medium the response to ouabain was not suppressed. The angiotensin II-induced changes in [Ca2+]i were diminished in Ca(2+)-free medium and by nifedipine, but enhanced by NiCl2. CONCLUSION: The increase in [Ca2+]i after Na+,K+ ATPase inhibition is not due to a modulation of Na(+)-Ca2+ exchange, but to a Ca2+ influx through Ca2+ channels. Changes in Na(+)-Ca2+ exchange caused by Na+,K+ ATPase inhibition may not play an important role in vascular smooth muscle cells of spontaneously hypertensive rats.

Animals↗
PubMed1994

Different calcium storage pools in vascular smooth muscle cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats.

OBJECTIVE: To evaluate whether the distribution of intracellular free calcium may be impaired in primary hypertension. DESIGN: Cytosolic free calcium and stored calcium were investigated in cultured vascular smooth muscle cells from spontaneously hypertensive rats (SHR). METHODS: The concentrations of intracellular and stored calcium were investigated in cultured vascular smooth muscle cells from spontaneously hypertensive rats aged 6 months from the Münster strain (SHR) and from age-matched normotensive Wistar-Kyoto (WKY) rats. Vascular smooth muscle cells were grown on coverslips, and fluorescence measurements of the intracellular calcium concentration were performed using fura-2. The different effects of thapsigargin, a selective Ca-ATPase inhibitor, and of angiotensin II (Ang II) on the calcium storage pools were investigated. RESULTS: In the absence of external calcium thapsigargin produced a dose-dependent transient increase in the concentration of intracellular calcium in vascular smooth muscle cells. The thapsigargin-induced maximum peak increase in the concentration of intracellular calcium was not significantly different in SHR and WKY rats. After depletion of the thapsigargin-sensitive calcium pools the addition of 100 nmol/l Ang II produced a rise in the concentration of intracellular calcium in vascular smooth muscle cells from SHR and WKY rats. Using vascular smooth muscle cells from the SHR the Ang II-induced increase in the concentration of intracellular calcium was not significantly different in the presence and absence of thapsigargin, indicating that the calcium pools depleted by thapsigargin and Ang II do not overlap significantly in vascular smooth muscle cells from SHR. In contrast, in the WKY rats the response to Ang II was significantly diminished after depletion of the thapsigargin-sensitive pool. When Ang II and thapsigargin were administered in the reverse order, i.e. Ang II before thapsigargin, the thapsigargin response was diminished in the WKY rats but not in the SHR. CONCLUSION: SHR differ from WKY rats in having vascular smooth muscle cells that contain thapsigargin-sensitive calcium storage pools that are distinct from the Ang II-sensitive calcium pools.

Angiotensin II↗
PubMed1994

Increased cytosolic free sodium in platelets from patients with early-stage chronic renal failure.

Cytosolic free sodium concentration ([Na+]i) and sodium transport systems were measured in intact platelets from 19 patients with early-stage chronic renal failure and 33 healthy control subjects using the novel fluorescent dye sodium-binding-benzofuran-isophthalate. Resting [Na+]i was significantly greater in patients with chronic renal failure compared to control subjects (40.8 +/- 3.1 mmol/l versus 32.2 +/- 2.0 mmol/l, mean +/- SEM, P < 0.05). After inhibition of Na-K-ATPase by 1 mmol/l ouabain a higher net sodium influx was observed in platelets from patients with chronic renal failure compared to control subjects (49.8 +/- 8.7 mmol/l versus 28.5 +/- 5.2 mmol/l, P < 0.05). The platelet Na-H exchanger was similar in the two groups. Cytosolic free calcium concentration ([Ca2+]i) was measured using fura2 and did not show significant differences between the two groups. To evaluate whether a circulating factor may be associated with elevated [Na+]i, a linked-enzyme Na-K-ATPase assay was included. Compared to control subjects plasma from patients with chronic renal failure produced a significant inhibition of steady-state Na-K-ATPase activity by 11.2 +/- 3.0% (P < 0.01). It is concluded that early-stage renal failure is associated with significant impairment of platelet sodium metabolism.

Adult↗
PubMed1993

Partial purification and characterization of a circulating hypertensive factor in spontaneously hypertensive rats.

Parabiosis and cross-circulation experiments with spontaneously hypertensive and normotensive rats gave indications for a previously unidentified circulating hypertensive agent. In this study, plasma from normotensive and hypertensive rats was fractionated and the vasopressor action of the corresponding fractions was measured in the isolated perfused rat kidney. One of three vasoactive fractions obtained by gel filtration (Biol-Gel P2) from hypertensive rats showed a significantly higher activity (increase in perfusion pressure by 1502.9 +/- 438.9 Pa) than that from normotensive rats (increase in perfusion pressure by 505.4 +/- 186.2 Pa, P < 0.01). Further chromatographic separations of this fraction revealed that the hypertensive factor is hydrophilic and has no ionic groups or vicinal diol groups. The molecular mass was estimated by dialysis and the matrix-assisted laser desorption/ionization mass spectrometry to be in the range of 1 kDa. The vasopressor is heat resistant and not degradable with trypsin or carboxypeptidase Y. The vasopressor action was not inhibited with the angiotensin-II-receptor antagonist saralasin, the alpha-receptor antagonist phentolamine, the thromboxane-receptor antagonist carbocyclic thromboxane A2 or the serotonin antagonist ketanserin. The results confirm the existence of a vasopressor factor in the plasma of hypertensive rats and, in a lower concentration, of normotensive rats, which is possibly related to the pathogenesis of essential hypertension. The chromatographic behavior suggests that this factor is different from the parathyroid hypertensive factor described recently.

Animals↗
PubMed1993

Effect of spironolactone on cytosolic free sodium concentration in platelets from hypertensive patients with primary aldosteronism.

Cytosolic free sodium concentration ([Na+]i) was investigated in intact platelets from 5 hypertensive patients with primary aldosteronism (unilateral adenoma in 3 patients, and adrenal hyperplasia in 2 patients) and 21 normotensive control subjects. [Na+]i was measured using a novel sodium-sensitive fluorescent dye technique. [Na+]i was significantly decreased in platelets from patients with primary aldosteronism compared to control subjects (21.9 +/- 4.1 mM vs 35.8 +/- 2.2 mM, mean +/- SEM, P < 0.05). After administration of the mineralocorticoid antagonist spironolactone in 4 patients [Na+]i tended to be higher in platelets although the differences did not reach statistical significance (26.3 +/- 7.2 mM vs 18.2 +/- 2.4 mM, P = 0.125). From the present results it may be concluded that intracellular sodium is decreased by aldosterone-induced activation of Na-K-ATPase. That activation may be partly blocked by spironolactone.

Aged↗
PubMed1993

Concentration-dependent effects of insulin on Ca2+ influx in vascular smooth muscle cells of normotensive and spontaneously hypertensive rats.

1. The effect of insulin on cytosolic free Ca2+ concentration was measured using fura-2 in vascular smooth muscle cells of normotensive and spontaneously hypertensive rats. 2. In both strains, insulin increased cytosolic free Ca2+ concentration in a concentration range between 10(-6) and 10(-3) units/ml. The maximum increase in cytosolic free Ca2+ concentration was observed with 10(-5) units/ml insulin (107 +/- 25 and 82 +/- 27 nmol/l in spontaneously hypertensive rats and normotensive rats, respectively). 3. The effect of insulin was dependent on extracellular Ca2+ and was enhanced by stimulation of protein kinase C. 4. Thus insulin appears to induce a Ca2+ influx in vascular smooth muscle cells only over a certain range of concentrations. No significant difference in the response to insulin of cells from normotensive and hypertensive rats was observed.

Angiotensin II↗
PubMed1993

Effect of cytokines on cytosolic-free calcium in human platelets from essential hypertensives.

The different effects of cytokines on cytosolic-free calcium concentration ([Ca2+]i) and intracellular stored calcium were investigated in platelets from 35 essential hypertensive patients (HT) and 45 age- and sex-matched normotensive control subjects (NT). Erythropoietin (EPO) and interleukin 2 significantly increased platelet [Ca2+]i, whereas platelet-derived growth factor, and fibroblast growth factor had no significant effect on [Ca2+]i. The EPO-induced rise of [Ca2+]i was significantly higher in HT compared to NT (15.2 +/- 4.3 nmol/L v 1.3 +/- 1.7 nmol/L, P < .01). Preincubation with EPO significantly increased calcium in intracellular stores in platelets from HT and NT. Inhibition of protein kinase C significantly enhanced EPO-induced rise of stored calcium. It is concluded that an increased response of HT to EPO may be associated with essential hypertension.

Adult↗
PubMed1993

Erythropoietin increases cytosolic free calcium concentration in vascular smooth muscle cells.

OBJECTIVES: The underlying pathophysiological mechanism leading to raised blood pressure after treatment with erythropoietin is a point of much discussion. Direct vasopressor effects of erythropoietin have been shown recently. The aim was to determine whether erythropoietin effects cytosolic free calcium concentration ([Ca2+]i in vascular smooth muscle cells. METHODS: The effect of erythropoietin on ([Ca2+]i was measured with the fluorescent dye fura2 in cultured vascular smooth muscle cells from Wistar Kyoto rats. RESULTS: Mean resting [Ca2+]i was 90.8(SEM 5.6) nM (n = 32). Addition of erythropoietin at concentrations of 100 U.ml-1 and 250 U.ml-1 increased [Ca2+]i to 112.3(5.0) nM (n = 23, p < 0.05) and 128.4(4.0) nM (n = 10, p < 0.01), respectively. Preincubation with erythropoietin caused a dose dependent increase in angiotensin II induced changes of [Ca2+]i in vascular smooth muscle cells. CONCLUSIONS: One mechanism of erythropoietin induced hypertension may be an increase in [Ca2+]i in vascular smooth muscle cells.

Animals↗
PubMed1993

Progression of distal-symmetric polyneuropathy in HIV infection: a prospective study.

OBJECTIVE: To investigate progression of distal-symmetric sensory polyneuropathy and its correlation to immunological development. METHODS: Clinical, neurophysiological and immunological parameters were followed in 42 HIV-infected patients for 13 +/- 6 months. Neurophysiological investigations were performed in the sural and peroneal nerve. Initially, 14 patients showed clinical signs of polyneuropathy (paresthesia, hypesthesia, diminution of vibration and deep ankle reflexes) compared with 28 patients at the end of the follow-up, 13 +/- 6 months later. RESULTS: All neurophysiological parameters deteriorated during the observation period. In 20 patients changes of plasma immunoglobulin (Ig) G, IgM, IgA levels, T-helper-, T-suppressor-, natural killer cell counts and plasma beta 2-microglobulin were determined. There was a significant correlation between the development of IgG, IgM, IgA and paired stimulation and conduction velocity of the sural nerve (Spearman's rank-correlation coefficient, P < 0.05). CONCLUSION: These results show that distal-symmetric polyneuropathy during HIV infection is rapidly progressive and related to immunological factors. It is assumed that immunological mechanisms play an important part in the pathogenesis of polyneuropathy during HIV infection.

Adult↗
PubMed1993

Angiotensin II responses after protein kinase C activation in vascular smooth muscle cells of spontaneously hypertensive rats.

To examine the interaction of protein kinase C (PKC) with agonist-induced calcium fluxes in hypertension, cytosolic free calcium ([Ca2+]i) was measured in vascular smooth muscle cells (vSMC) of normotensive and spontaneously hypertensive rats (SHR) after incubation with phorbol,-12 myristate,-13 acetate (PMA) and application of angiotensin II (AII). To distinguish between calcium influx through voltage-dependent calcium channels and calcium mobilization from intracellular stores, the calcium agonist BayK 8644 was used. Resting [Ca2+]i was 108.0 +/- 10.6 nM (mean +/- SEM, n = 25) in normotensive and 102.0 +/- 11.4 nM (n = 21) in hypertensive cells. After pretreatment with PMA 10(-7) M for 60 min, resting [Ca2+]i of normotensive vSMC increased to 145.0 +/- 13.8 nM (n = 17) while the resting level of the hypertensive cells decreased to 68.0 +/- 2.4 nM (n = 14, p < 0.05 as compared with normotensive cells) in hypertensive vSMC. Maximum increase in [Ca2+]i induced with 10 M AII for normotensive and hypertensive vSMC was similar: 230.5 +/- 34.4 nM (n = 14) and 212.5 +/- 26.7 nM (n = 17). After pretreatment with PMA 10(-7) M, the maximum increase in [Ca2+]i induced by AII in hypertensive cells was limited to 108.0 +/- 6.2 nM (p < 0.05 as compared with normotensive cells), whereas the increase in [Ca2+]i in normotensive vSMC remained the same as before: 211.5 +/- 23.4 nM. After administration of 10(-5) M BayK 8644, [Ca2+]i increased by 54.3 +/- 12.2 nM (n = 4) and 43.4 +/- 17.4 nM (n = 5) in normotensive and hypertensive vSMC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Effect of long-term hemodialysis on arterial compliance in end-stage renal failure.

To assess the influence of long-term hemodialysis on arterial compliance, the elastic vessel wall properties of the common carotid artery were determined in 20 normotensive renal transplant recipients (age 44.7 +/- 4.1 years) 8-12 weeks after first transplantation and in 10 healthy controls (age 45.9 +/- 5.2 years). Arterial distension was measured by using a multigate pulsed Doppler system, blood pressure curve was recorded by finger-plethysmography. 10 patients with a prior long-term hemodialysis of 51 +/- 11 months were compared to 10 patients with a prior short hemodialysis of 18 +/- 7 months. The patients and controls had been matched in respect of age, sex and blood pressure. In the long and short-term hemodialysis group, the proportion of patients (n = 10) with a history of mild hypertension was similar--mild hypertension for 25 +/- 10 months (n = 5) and for 27 +/- 9 months (n = 5). In the group with long-term hemodialysis, the cross-sectional compliance and the distensibility coefficient was significantly reduced in comparison to the group with short-term hemodialysis (p < 0.005) and to the control group (p < 0.001). A significant inverse correlation between the hemodialysis period and the distensibility coefficient (r = -0.59; p < 0.005) showed a decrease in arterial compliance with the length of hemodialysis treatment. The results demonstrate that vessel wall elasticity decreases with the length of hemodialysis treatment and is reduced by hemodialysis-dependent factors, which are detached from sustained arterial hypertension. As cause of reduced arterial compliance in long-term hemodialysis hypervolemia, hypercirculation and disturbed calcium-phosphate metabolism is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of captopril on vasoconstriction and Ca2+ fluxes in aortic smooth muscle.

The effects of captopril on the response of cytosolic free Ca2+ concentration in cultured vascular smooth muscle cells of aortas from Wistar-Kyoto and spontaneously hypertensive rats to angiotensin II (Ang II) and bradykinin were studied using fura 2. Incubation with captopril for longer than 10 minutes caused a decreased response of cytosolic free Ca2+ to Ang II and bradykinin. Maximal effects of captopril were observed after a 40-minute incubation. The inhibitory effect of captopril was abolished in Ca(2+)-free medium, suggesting that captopril acts by blocking Ca2+ influx. Similar effects were observed with enalaprilat. Isometric contraction of aortic strips induced by Ang II in normotensive rats was reduced from 6.5 +/- 2.5 to 1.8 +/- 0.6 mN by a 40-minute incubation with 1 mumol/L captopril (P = .016). Enalaprilat similarly decreased the Ang II-induced contraction. Besides the inhibition of the angiotensin converting enzyme, direct effects of Ang II converting enzyme inhibitors on vascular contraction and Ca2+ influx in vascular smooth muscle cells may be of therapeutic relevance.

Analysis of Variance↗
PubMed1993

Increased cytosolic free sodium concentrations in platelets from type 2 (non-insulin-dependent) diabetic patients is associated with hypertension.

Cytosolic free sodium concentrations ([Na+]i) in intact platelets from 32 type 2 (non-insulin-dependent) diabetic patients and from 27 age- and sex-matched non-diabetic control subjects were measured with the novel sodium-sensitive fluorescent dye sodium-binding-benzofuran-isophthalate. [Na+]i was significantly higher in platelets from type 2 diabetic patients compared with control subjects (40.6 +/- 2.4 vs 32.0 +/- 2.0 mmol/l, means +/- S.E.M., P < 0.03). Both systolic and diastolic blood pressure were significantly elevated in diabetic patients compared with control subjects. Analysis of diabetic patients showed a significant association between [Na+]i and diastolic blood pressure (P = 0.026). Stimulation of Na/H exchange by thrombin increased [Na+]i in both groups. After inhibition of Na/K/ATPase by ouabain (1 mmol/l), [Na+]i was significantly increased both in diabetic patients and non-diabetic subjects in a similar way (by 40.2 +/- 7.3 and 31.7 +/- 5.3 mmol/l respectively). It is concluded that increased [Na+]i in cells from type 2 diabetic patients may be related to hypertension.

Adult↗
PubMed1993

Circadian blood pressure variations in endocrine disorders.

Circadian rhythm of blood pressure and of heart rate was studied in patients with hyperthyroidism (n = 10), pheochromocytoma (n = 8), primary hyperaldosteronism (n = 7), and in a control group of essential hypertensive patients (n = 18) and of normotensive healthy subjects (n = 11). 24-hour blood pressure was monitored non-invasively using SpaceLabs (SL 90207) with 8-min intervals in the daytime (8 a.m. to 10 p.m.) and 30-min intervals during night-time (10 p.m. to 8 a.m.). To characterize circadian blood pressure rhythm the difference between the mean blood pressure during daytime and that during night-time was calculated. In patients with hyperthyroidism the day-night difference of the systolic and diastolic blood pressure and of the heart rate was significantly reduced when compared to the normotensive control group (p < 0.05). The day-night difference of the systolic and diastolic blood pressure was significantly lower in the group with pheochromocytoma and hyperthyroidism than in the essential hypertensive controls (p < 0.05); the day-night difference of the heart rate was similar. In the patients with primary hyperaldosteronism the day-night differences of the systolic and diastolic blood pressure and of the heart rate was similar to those in essential hypertensive controls. We conclude that endocrine disorders affecting sympathetic activity like pheochromocytoma or hyperthyroidism influence the circadian blood pressure rhythm, whereas the renin-aldosterone-system has no major impact on the diurnal blood pressure variation. The results therefore support the hypothesis that circadian blood pressure variation is mainly mediated by a modulation of the sympathetic tone.

Adrenal Gland Neoplasms↗
PubMed1993

Ca2+ ATPase activity in essential and renal hypertension.

In 15 patients with essential hypertension, 16 patients with renal hypertension and in 12 healthy subjects Ca2+ ATPase activity was determined in red blood cells both in the basal state and after maximal stimulation with calmodulin. Normal subjects showed a basal and maximal activity of 7.1 +/- 3.6 and 16.0 +/- 2.3 pmol phosphate/min.10(6) RBC, respectively. Renal hypertensives had a similar basal Ca2+ ATPase activity (5.4 +/- 4.1 pmol phosphate/min.10(6) RBC) and a lowered maximal Ca2+ ATPase activity (9.8 +/- 5.4 pmol phosphate/min.10(6) RBC, p < 0.05). In essential hypertensives basal and maximal Ca2+ ATPase activity was 9.0 +/- 5.3 and 35.4 +/- 14.4 pmol phosphate/min.10(6) RBC, respectively, the latter being significantly increased (p < 0.01). This finding, which is in contrast to earlier results indicating a lowered Ca2+ ATPase activity in essential hypertension, may be explained as a consequence of an increased Ca2+ influx in essential hypertension. A lowered Ca2+ ATPase activity does not seem to be involved in the pathogenesis of essential hypertension.

Adult↗
PubMed1993

New data about the effects of oral physiological magnesium supplementation on several cardiovascular risk factors (lipids and blood pressure).

In the present study the effect of oral physiological magnesium supplementation on atherogenic risk factors such as serum lipids and blood pressure was examined. Sixty-nine patients with hyperlipidaemia of Frederickson types IV and IIb were investigated with regard to renal function, blood pressure, serum cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol, and plasma and erythrocytic magnesium concentrations. All patients were on cholesterol-poor (< 90 mg cholesterol/d) and energy-restricted diet (< 1200 kcal/d). Thirty-seven patients received 500 mg magnesium (oral) daily as a supplement. All measurements were performed before and four weeks after starting treatment. The results of our study show that oral physiological magnesium supplementation in addition to the usual dietary measures can be beneficial with regard to serum triglycerides (values, means +/- SD, decreased from 198.17 +/- 47.01 to 163.20 +/- 40.55 mg/dl, P < 0.05), but exerts no positive effect on blood pressure or serum cholesterol. Furthermore, erythrocyte magnesium concentration increased significantly during oral physiological magnesium supplementation (values, means +/- SD, increased from 1.72 +/- 0.22 to 1.91 +/- 0.18 mmol/litre, P < 0.05), whereas plasma magnesium concentrations did not change significantly.

Blood Pressure↗