Patients with end-stage renal disease show disturbances of calcium metabolism, including calcification of arterial walls. Such patients show increased mortality, in particular due to increased cardiovascular-associated deaths. The association of calcium channel blockers and mortality in patients undergoing haemodialysis was investigated. A total of 188 patients who were receiving haemodialysis as of July 1998 were followed up for 30 months. Baseline characteristics, including age, sex, laboratory and clinical data, medication and dialysis prescription, were obtained. As of December 2000, 51 of the patients (27%) had died. In the deceased group, age was significantly higher, body mass index was significantly lower, and smoking was significantly more frequent compared with the survival group (each P <0.001). The percentage of patients taking calcium channel blockers was significantly higher in the survival group. Cox proportional hazard regression analysis showed that haemodialysis patients assigned calcium channel blocker therapy had a significantly lower risk of mortality [relative risk 0.33 (95% confidence interval 0.17–0.67); P <0.001]. Thus, in haemodialysis patients who were at high risk of cardiovascular events, administration of calcium channel blockers was associated with lower mortality.

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 Mg 2+ and Na + concentrations in aortic cryosections 3 ; μ m thick. The Mg 2+ 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 Mg 2+ 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 Mg 2+ 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 Mg 2+ –Na + exchanger can be altered in a subgroup of SHR.

1. Low ouabain concentrations in the nanomolar range significantly increased cytosolic free calcium concentration. 2. The ouabain-induced cytosolic free calcium concentration increase was due to transplasmamembrane calcium influx, which could be prevented in the absence of extracellular calcium or by addition of the calcium channel blocker nifedipine. 3. The amount of stored cellular Ca 2+ , as determined by the thapsigargin-induced cytosolic free calcium concentration increase, was also enhanced by 1 nmol/l ouabain. 4. It is concluded that low ouabain concentrations affect intracellular cytosolic free calcium concentration homoeostasis.

1. Cytosolic free sodium concentration and sodium transport systems were measured in intact cultured vascular smooth muscle cells from spontaneously hypertensive rats of the Münster strain and from normotensive Wistar—Kyoto rats using the sodium-sensitive fluorescent dye sodium-binding benzofuran isophthalate. 2. Resting cytosolic free sodium concentration was significantly lower in vascular smooth muscle cells from spontaneously hypertensive rats than from Wistar-Kyoto rats (10.2 ± 1.5 mmol/l, n = 26, versus 19.4 ± 2.5 mmol/l, n = 20, P < 0.01). 3. Inhibition of Na + , K + -ATPase by ouabain caused a dose-dependent increase in cytosolic free sodium concentration in spontaneously hypertensive rats and Wistar—Kyoto rats. 4. Activation of Na + -Ca 2+ exchange by ionomycin increased cytosolic free sodium concentration in both strains. However, the ionomycin-induced increase in cytosolic free sodium concentrations was significantly higher in vascular smooth muscle cells from spontaneously hypertensive rats than from Wistar—Kyoto rats (220 ± 35% of the resting cytosolic free sodium concentration versus 148 ± 27%; P < 0.05). The ionomycin-induced increase in cytosolic free sodium concentration was prevented in the absence of external sodium or by inhibition of Na + -Ca 2+ exchange by NiCl 2 . 5. Activation of Na + -H + exchange by intracellular acidification of vascular smooth muscle cells with propionic acid increased cytosolic free sodium concentration in each strain (19.6 ± 5.7 versus 16.3 ± 3.2 mmol/l). 6. It is concluded that concepts concerning the role of cytosolic free sodium concentration in the pathogenesis of primary hypertension need to be reinvestigated. However, the conclusions from results obtained in cultured vascular smooth muscle cells are limited with respect to conditions in vivo .

1. The effect of insulin on cytosolic free Ca 2+ 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 Ca 2+ concentration in a concentration range between 10 −6 and 10 −3 units/ml. The maximum increase in cytosolic free Ca 2+ 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 Ca 2+ and was enhanced by stimulation of protein kinase C. 4. Thus insulin appears to induce a Ca 2+ 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.

1. Isolated perfused rat kidneys were used to study the effects of plasma fractions obtained by gel filtration from essential hypertensive patients ( n = 40) and from normotensive subjects ( n = 36) on resistance vessels. Perfusion pressure was recorded at a constant flow. 2. Plasma fractions were obtained by gel filtration and contained substances with a molecular mass in the range 1000–1500 Da. The plasma fractions from hypertensive patients used in this study had been shown to increase blood pressure after intravenous injection in rats. 3. In the isolated rat kidneys, the hypertensive fractions increased perfusion pressure by 20 ± 17 mmHg (mean ± SD, range 5–58 mmHg, n = 40). The analogous fractions from normotensive subjects did not change perfusion pressure significantly. 4. In Ca 2+ -free medium containing 2 mmol/l ethyleneglycol bis-(aminoethyl ether)tetra-acetate, the change in perfusion pressure induced by active plasma fractions was reduced by 95.2 ± 6.3%. Addition of nifedipine to the perfusion medium reduced, but did not abolish, the pressure response of the kidneys. 5. In solutions containing phentolamine or saralasin, vasoconstriction was not reduced. 6. Thus in the active fractions from hypertensive plasma, a vasopressor agent with direct action on resistance vessels can be demonstrated. This substance probably acts by increasing Ca 2+ influx in vascular smooth muscle cells.

1. The effects of plasma fractions from essential hypertensive subjects ( n = 14) and normotensive subjects ( n = 14) on Ca 2+ transport in permeabilized human neutrophils was studied using an ion-selective electrode. 2. Plasma fractions were obtained by gel filtration and contained substances with a molecular mass in the range 1000–1500 daltons. This fraction isolated from essential hypertensive subjects has been shown to increase blood pressure after intravenous injection in the rat. 3. The rate of Ca 2+ uptake by permeabilized neutrophils after addition of extracellular Ca 2+ was significantly accelerated during incubation of the cells with the hypertensive fraction (1049.3 ±807.7% vs 242.5 ±320.9% of the control value, mean ± sd , P < 0.05). 4. It is concluded that the hypertensive plasma fraction increases Ca 2+ accumulation in subcellular particles, so that under excitatory conditions Ca 2+ release in arterial smooth muscle might be enhanced.