[Combination therapy with ACE inhibitors and angiotensin receptor antagonists].
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Biomedical subjects
Publications and source records attributed to K Kisters.
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Intracellular Mg2+ measurements were performed in erythrocyte membranes of 18 untreated normotensive and 19 untreated essential hypertensive patients. Mg2+ concentrations were determined by atomic absorption spectroscopy using a Video 12 apparatus. The results show that in patients with essential hypertension total Mg2+ content in erythrocyte membranes was significantly decreased as compared with the control group (0.28 +/-0.05 v 0.52+/-0.15 mmol/g membrane protein; mean+/-SD, P < .001). Additionally, plasma and free intracellular Mg2+ content of lymphocytes and platelets showed no significant difference in normotensives and hypertensives. Lowered total membrane Mg2+ concentrations in a subgroup of primary hypertensives may contribute to the development of this disorder, perhaps due to different buffering or membrane transport systems.
The mechanisms responsible for reduced arterial distensibility in renal transplant recipients remain to be evaluated. The present longitudinal study was aimed to evaluate the effect of hypertension on the evolution of vessel wall properties in renal transplant recipients. The mechanical properties of the common carotid artery were determined in 24 normotensive and 24 treated hypertensive renal transplant recipients 6-12 weeks after transplantation. The measurements were repeated after 2 years. Arterial distension was determined by using a multigate pulsed Doppler system, blood pressure (BP) was measured by a mercury sphygmomanometer. BP was 127 +/- 3/80 +/- 2 mm Hg at entry and 133 +/- 3/82 +/- 2 mm Hg after 2 years in the normotensive group, 146 +/- 4/90 +/- 3 mm Hg at entry and 145 +/- 3/87 +/- 2 mm Hg after 2 years in the hypertensive group (P < 0.01, normotensives vs hypertensives). The distensibility coefficient (DC) decreased significantly after 2 years in the hypertensive group (DC 18.3 +/- 1.3 10(-3)/kPa before, 15.1 +/- 1.2 10(-3)/kPa after 2 years, P < 0.05) whereas no significant change was observed in the normotensive group (DC 19.0 +/- 1.4 10(-3)/kPa before, DC 17.8 +/- 1.3 10(-3)/kPa after 2 years, NS). There was a significant correlation between the change of the distensibility coefficient after 2 years and mean arterial pressure (n = 48, r = 0.42, P < 0.01). The results show that the decrease of arterial distensibility after 2 years is accelerated in hypertensive renal transplant recipients despite effective anti-hypertensive treatment. Since BP levels were not different at entry into the study and after 2 years, differences in distending pressure along cannot explain the more pronounced decrease of arterial distensibility over time in hypertensive renal transplant recipients.
1. Although in blood cells decreased magnesium concentrations and increased sodium concentrations in essential hypertension have often been described, only sparse data exist on cellular magnesium or sodium content and exchange in vascular smooth muscle cells.2. Therefore in aortic smooth muscle cells from 10 spontaneously hypertensive rats (SHR) of the Münster strain and 10 normotensive Wistar-Kyoto rats (WKY) aged 3 and 8-10 months, the intracellular magnesium and sodium content was measured.3.Electron-probe X-ray microanalysis was used to determine intracellular Mg2+ and Na+ concentrations in aortic cryosections 3 micron thick. The Mg2+ content was 47+/-13 mmol/kg dry weight in SHR versus 48+/-19 mmol/kg dry weight in WKY aged 3 months, and 37+/-6 mmol/kg dry weight in SHR versus 47+/-4 mmol/kg dry weight in WKY aged 8-10 months (P<0. 05). Vascular smooth muscle Na+ content was 283+/-59 mmol/kg dry weight in WKY and 402+/-123 mmol/kg dry weight in SHR aged 3 months (P<0.05), and 289+/-17 mmol/kg dry weight in WKY versus 548+/-39 mmol/kg dry weight in SHR aged 8-10 months (P<0.05).4. Aortic smooth muscle cells from SHR are characterized by a markedly lower intracellular Mg2+ content in 8-10-month-old animals and increased Na+ concentrations compared with normotensive cells in 3- and 8-10-month-old rats. The results may be due to genetically determined disturbances in transmembrane Mg2+ and Na+ transport. Cellular magnesium and sodium handling may be disturbed in SHR aortic smooth muscle as it is in hypertensive blood cells. In addition, it is concluded that vascular smooth muscle cell Mg2+-Na+ exchanger can be altered in a subgroup of SHR.
BACKGROUND: The cushioning function of the arterial system is altered in patients with end-stage renal failure. The role of hyperparathyroidism for the altered vessel wall properties of large arteries not known. METHODS: To exclude the confounding effects of fluid volume changes and hypercirculation as well as uremic toxicity on vessel wall properties from those of hyperparathyroidism, the present study was conducted in 54 normotensive renal transplant recipients with good graft function, three to six months after transplantation. The vessel wall properties of the common carotid artery were investigated in 32 of them, who had increased plasma intact parathyroid hormone (iPTH) levels (136 +/- 12 ng/liter, SEM), and compared to those of 22 control recipients of same age with normal plasma iPTH levels (34 +/- 4 ng/liter). Arterial distension was measured by Doppler analysis of the vessel wall movements, blood pressure was determined by sphygmomanometry. RESULTS: Blood pressure was 140 +/- 3/85 +/- 2 mm Hg in renal transplant recipients with hyperparathyroidism, 135 +/- 3/83 +/- 1 mm Hg in patients with normal plasma iPTH levels (NS). There was no difference in enddiastolic diameter of the common carotid artery (7.4 +/- 0.2 mm) in renal transplant recipients with hyperparathyroidism as compared with the control patients (7.3 +/- 0.2 mm; NS). Renal transplant recipients with hyperparathyroidism had a lower distension (389 +/- 27 microns vs. 486 +/- 28 microns, P < 0.05) and distensibility coefficient of the common carotid artery (15.1 +/- 1.1 10(-3)/kPa vs. DC 19.0 +/- 1.0 10(-3)/kPa, P < 0.001) when compared with the control patients. Multiple regression analysis showed that the distensibility coefficient of the common carotid artery was negatively correlated with age (P < 0.001), mean arterial blood pressure (P < 0.05) and plasma iPTH levels (P < 0.05). The effects of plasma iPTH levels were not related to serum calcium concentrations or to differences in the enddiastolic diameter of the common carotid artery. CONCLUSIONS: The data suggest that secondary hyperparathyroidism can affect the cushioning function of larger arteries in patients with end-stage renal failure independently of high blood pressure.
OBJECTIVE: Changes in intracellular Ca2+ and Mg2+ concentrations seem to be involved in the pathogenesis of preeclampsia, whereas the role of cell membranes has not been studied in detail yet. To investigate the changes in Ca2+ and Mg2+ metabolism in normal pregnancy and preeclampsia, plasma and membrane Ca2+ and Mg2+ concentrations were determined in a clinical study as compared to healthy subjects. STUDY DESIGN: 25 healthy female subjects, 22 untreated healthy pregnant and 20 preeclamptic women were investigated. In each patient, plasma and membrane Ca2+ and Mg2+ content were measured. Ca2+ and Mg2+ concentrations were measured by atomic absorption spectroscopy. Erythrocyte membranes were chosen for membranous Ca2+ and Mg2+ determination. RESULTS: Plasma Mg2+ concentrations were significantly lowered in the healthy pregnant group and the preeclamptic group as compared to controls (p < 0.0001). In erythrocyte membranes, Mg2+ content was found significantly decreased in the preeclamptic women as compared to healthy subjects (p < 0.001). In plasma Ca2+ concentrations there was a significant decrease in the preeclamptic group as compared to controls or healthy pregnant women (p < 0.05). Membranous Ca2+ content was significantly increased in the preeclamptic group versus controls or healthy pregnant women (p < 0.001). CONCLUSION: Lowered plasma and membrane Mg2+ concentrations in preeclampsia may contribute to the development of hypertension in pregnancy. Additionally, a disturbed Ca2+ homeostasis is observed in preeclampsia.
From July 1996 to November 1997 13 patients underwent "two-in-one"-kidney transplantation from marginal donors. Up to now all renal grafts show a stable function measuring an average creatinin of 1.73 mg/dl after an average follow up of 8.2 month. To take the decision between "one-in-one" or "two-in-two" transplantation in marginal donors we developed a specific score. This score needs more evaluation because of the still small amount of patients undergoing double-kidney-transplantation.
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A new method to determine total Mg2+ content in lymphocytes was developed, offering advantages for routine measurements as compared to fluorescence methods. Intracellular Mg2+ measurements were performed in lymphocytes of 18 untreated normotensive and 19 untreated essential hypertensive patients. Mg2+ content was referred to lymphocytic protein, which was determined according to Bradford's method. Mg2+ measurements were performed by atomic absorption spectroscopy using a Video 12 apparatus from Thermo Electron Instrumentation Laboratory, Andover, MA, USA. The results show that in patients with essential hypertension, total intralymphocytic Mg2+ content is significantly lower (0.07 +/- 0.05 mmol/g lymphocytic protein, mean +/- s.d.) as compared to controls (0.11 +/- 0.04 mmol/g lymphocytic protein, mean +/- s.d., P < 0.05). Free intracellular Mg2+ content was measured in lymphocytes by the fluorescent indicator mag-fura-II, showing no significant difference in normotensives and hypertensives (0.30 +/- 0.16 vs 0.38 +/- 0.17 mmol/l). In platelets free intracellular Mg2+ concentrations were not found of significant difference in normotensive and hypertensive patients (0.52 +/- 0.23 vs 0.47 +/- 0.27 mmol/l) using mag-fura-II. In plasma Mg2+ concentrations there was no significant difference in the normotensive and hypertensive group (0.92 +/- 0.07 vs 0.88 to 0.07 mmol/l). There was no correlation between plasma, free or total cellular magnesium concentrations in each group. Furthermore this method also seems suitable for routine measurements of total intracellular Mg2+ concentrations in even larger groups of patients in comparison with fluorescent indicator measurements like mag-fura-II. Lowered total intracellular Mg2+ concentrations in a subgroup of primary hypertension may contribute to the development of this disorder, perhaps due to different buffering systems.
The effects of oral glucose challenge on plasma glucose concentration, plasma insulin concentration, arterial blood pressure, cytosolic pH (pHi), cytosolic free Na+ concentration ([Na+]i), and cellular Na(+)-H+ exchange activity were investigated in 16 healthy subjects. The pHi, [Na+]i, and Na(+)-H+ exchange activity were measured in intact lymphocytes by using the fluorescent dye technique. The oral glucose challenge significantly increased plasma glucose, plasma insulin, and the lymphocytic Na(+)-H+ exchange activity, measured as change of pHi per second (control [0 hours], 5.20 +/- 0.53 x 10(-3) dpHi/s; 1 hour after glucose administration, 8.28 +/- 1.07 x 10(-3) dpHi/s; 2 hours after glucose administration, 8.15 +/- 1.18 x 10(-3) dpHi/s; P = .002). The lymphocytic Na(+)-H+ exchange was significantly correlated with plasma glucose concentration (r = .357, P = .041). During steady state euglycemic hyperinsulinemic clamp, the Na(+)-H+ exchange activity was not significantly changed compared with baseline values. The study shows that changes of blood glucose levels can induce an acute increase in Na(+)-H+ exchange activity. Systolic blood pressure and Na(+)-H+ exchange activity were significantly (P < .001) but weakly correlated during an oral glucose challenge.
Plasma magnesium, cytosolic (lymphocytic) and membrane (erythrocytic) magnesium concentrations were determined in 15 controls with normal renal function compared to 12 patients with renal insufficiency (chronic glomerulonephritis, serum creatinine 2.5 +/- 0.8 mg/dl, mean +/- SD). Plasma magnesium concentrations were determined by atomic absorption spectroscopy (AAS), cytosolic free magnesium with the fluorescent indicator Mag-Fura-2, and membrane magnesium by AAS, referred to membrane protein content which was determined according to Bradford's method. Plasma magnesium was 0.91 +/- 0.08 mmol/litre in controls versus 0.95 +/- 0.09 mmol/litre in renal-insufficient patients. Cytosolic free magnesium content was 2.38 +/- 0.75 mmol/litre in controls and 2.61 +/- 0.35 mmol/litre in the renal-insufficient group. In the renal-insufficient group membrane magnesium concentrations were found to be significantly increased as compared to the control group (2.85 +/- 0.62 vs 0.53 +/- 0.22 mmol/g membrane protein, mean +/- SD, P < 0.05). The results show that cell membranes may be of special importance in renal insufficiency in avoiding magnesium overload of the cell and in keeping free cytosolic magnesium stores stable.
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.
1. Calcium concentration and Ca(2+)-ATPase activity under basal conditions and after maximal stimulation with calmodulin were measured in erythrocytes from 32 patients with end-stage renal failure on haemodialysis and from 27 healthy subjects. 2. In patients with renal failure the Ca2+ concentration in erythrocytes was elevated compared with healthy subjects (4.27 +/- 1.02 versus 2.86 +/- 0.57 mumol/l, P less than 0.05). 3. Basal Ca(2+)-ATPase activity was lower in the patients with renal failure than in healthy subjects (4.62 +/- 1.34 versus 5.43 +/- 1.23 pmol of phosphate min-1 10(-6) erythrocytes). After maximal stimulation, Ca(2+)-ATPase activity reached 6.93 +/- 2.81 pmol of phosphate min-1 10(-6) erythrocytes in the patients with renal failure, whereas in healthy subjects stimulation yielded a Ca(2+)-ATPase activity of 32.54 +/- 8.48 pmol of phosphate min-1 10(-6) erythrocytes. 4. Incubation of erythrocytes from healthy subjects with plasma from uraemic patients caused inhibition of Ca(2+)-ATPase. Likewise, the ultrafiltrate from plasma obtained by haemofiltration treatment inhibited Ca(2+)-ATPase. 5. Gel chromatography of the ultrafiltrate and laser desorption/ionization mass spectroscopy revealed that a fraction containing substances with a molecular mass of about 300 Da inhibited Ca(2+)-ATPase. 6. It is concluded that, in uraemia, a Ca(2+)-ATPase inhibitor accumulates in the plasma, and this could contribute to the toxicity of uraemia by inhibiting cellular Ca2+ transport in erythrocytes and possibly other tissues.
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Plasma and intra-erythrocytic magnesium concentrations were determined in 27 patients with pre-eclampsia and in 22 healthy pregnant women. In the pre-eclamptic women, the Mg2+ concentrations were measured before and after treatment with Mg2+ salts and after delivery. The plasma Mg2+ concentration was not significantly different in the pre-eclamptic and the healthy pregnant women. The intra-erythrocytic Mg2+ concentration before treatment with Mg2+ was significantly lower in the pre-eclamptic patients than in the healthy pregnant women [1.33 +/- 0.29 versus 1.01 +/- 0.16 mmol/l (means +/- s.d.); P less than 0.05] and increased after treatment with Mg2+ to 1.19 +/- 0.24 mmol/l. Lowered cellular Mg2+ concentrations in pre-eclampsia may contribute to the development of hypertension in this disorder.
While diuretic-induced changes of plasma electrolyte concentrations have often been described, comparatively few data exist on intracellular electrolyte concentrations under diuretic treatment. Therefore, we studied the effect on intracellular Mg2+, Na+ and K+ concentrations of a thiazide diuretic (trichlormethiazide 4 mg/d) in red blood cells of 14 patients with mild essential hypertension, and of a combination of a thiazide diuretic and a potassium-sparing diuretic (trichlormethiazide and amiloride 2 mg/d each) in red blood cells of 11 patients with mild essential hypertension. Measurements were performed by atomic absorption spectroscopy and flame photometry before starting treatment and after 4 and 8-12 weeks' diuretic treatment. There was no significant change in intracellular Na+ and K+ concentrations under either form of diuretic treatment. Intracellular Mg2+ concentrations decreased significantly under thiazide therapy, whereas there was a significant increase in intracellular Mg+ concentrations under thiazide and potassium-sparing combined diuretic therapy. The results show that the combination of a thiazide diuretic and a potassium-sparing diuretic is a useful means to avoid intracellular Mg2+ loss.