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Biomedical subjects

M Tepel

Publications and source records attributed to M Tepel.

At least 127 records · Page 7Linked to original sources
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

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

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 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

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↗
PubMed1992

Erythropoietin induced transmembrane calcium influx in essential hypertension.

The effects of erythropoietin (EPO) on cytosolic free calcium concentration ([Ca2+]i) in platelets of 20 essential hypertensive patients (HT) and of 25 normotensive subjects (NT) were investigated using the fura2 technique. In resting platelets [Ca2+]i were not significantly higher in HT compared to NT (74.3 +/- 7.8 nM vs 59.8 +/- 7.0 nM, mean +/- SEM). Addition of EPO significantly increased [Ca2+]i in HT compared to NT (13.8 +/- 5.3 nM vs 0.9 +/- 1.9 nM, p less than 0.01). EPO increased the amount of calcium in intracellular stores. This was confirmed independently using thrombin-induced changes of [Ca2+]i in a calcium-free medium and using chlorotetracycline as a marker of stored calcium. After preincubation with EPO thrombin-induced changes of [Ca2+]i were significantly lower in HT compared to NT (306.1 +/- 30.0 nM vs 407.7 +/- 35.7 nM, p less than 0.05). In a calcium-free medium after preincubation with EPO thrombin-induced changes of [Ca2+]i were significantly lower in HT compared to NT (54.7 +/- 11.8 nM vs 100.9 +/- 10.5 nM, p less than 0.05) indicating lower storage capacity in HT. It is concluded that elevated response to EPO may provide a powerful tool to evaluate diagnosis and underlying pathophysiological mechanisms in essential hypertension.

Adult↗
PubMed1992

Effect of inhibition of Na, K-ATPase on cytosolic free sodium and calcium in platelets of spontaneously hypertensive rats.

Cytosolic free sodium concentrations ([Na+]i) in intact platelets of 18 spontaneously hypertensive rats (SHR) and of 18 age-matched normotensive Wistar-Kyoto rats (WKY) were measured using the sodium-sensitive fluorescent dye sodium-binding-benzofuran-isophthalate. In resting platelets [Na+]i tended to be higher in SHR compared to WKY (20.5 +/- 3.5 mmol/L v 15.1 +/- 1.9 mmol/L, mean +/- SEM), but the differences were not statistically significant. Stimulation of the Na-H-exchange by 1.0 U/mL thrombin increased [Na+]i in SHR by 22.9 +/- 4.3 mmol/L and in WKY by 35.0 +/- 5.6 mmol/L in a similar way. After inhibition of Na, K-ATPase by 1 mmol/L ouabain there was a significant rise of [Na+]i both in platelets of SHR to 38.0 +/- 5.1 mmol/L (P < .01 compared to resting platelets) and in platelets of WKY to 26.5 +/- 4.3 mmol/L (P < .01). However, no significant difference could be observed between these two groups. Using the calcium-sensitive dye fura-2, resting cytosolic free calcium concentrations ([Ca2+]i) were found to be significantly higher in platelets of SHR compared to WKY (171.9 +/- 21.5 nmol/L v 93.14 +/- 19.7 nmol/L, P < .05). After the addition of ouabain [Ca2+]i was significantly higher in SHR compared to WKY (245.5 +/- 32.6 nmol/L v 159.6 +/- 22.5 nmol/L, P < .05). The results do not support the hypothesis that altered sodium-calcium exchange causes elevated cytosolic free calcium in SHR.

Animals↗
PubMed1992

Reduced cytosolic free Na+ concentration in intact platelets of essential hypertensives.

OBJECTIVE: The role of intracellular Na+ concentration in the pathogenesis of essential hypertension is a point of considerable discussion. DESIGN: Since the novel fluorescent dye technique offers the possibility of measuring cytosolic free Na+ concentration in intact living cells, the role of Na+ was reinvestigated in resting and stimulated human platelets. METHODS: Cytosolic free Na+ concentration was measured in intact blood platelets of 20 essential hypertensive patients and 21 age- and sex-matched normotensive control subjects using the fluorescent dye Na(+)-binding benzofuran isophthalate. RESULTS: Cytosolic free Na+ concentration was significantly reduced in hypertensives compared with normotensives. Inhibition of Na+,K(+)-adenosine triphosphatase by ouabain elevated cytosolic free Na+ concentration in hypertensives and normotensives in a similar way. Addition of thrombin increased cytosolic free Na+ concentration both in hypertensives and normotensives. CONCLUSIONS: Previous concepts concerning the role of Na+ in the pathogenesis of essential hypertension based upon measurements in destructed cells need to be reinvestigarted using new techniques in living cells.

Adult↗