Direct effect of erythropoietin on rat vascular smooth-muscle cell via a putative erythropoietin receptor

BACKGROUND.: The treatment of uraemic patients with recombinant human erythropoietin(rHuEpo) often leads to an increase in blood pressure. Indirectand direct effects of the hormone are probably involved. Weexplored the possibility of a direct action on the vascularsmooth muscle cell (VSMC). METHODS.: Rat VSMC were isolated from aortas of spontaneously hypertensiverats (SHR) and normotensive control rats (WKY) and maintainedin culture. They were exposed to rHuEpo under various experimental conditions, and cells proliferative index was measuredby [³H]-thymidine incorporation. Binding studies and Northernblots were performed in an attempt to identify a specific erythropoietinreceptor (EpoR). In the latter experiment, Epo-responsive RauscherReds cells (Reds cells) were used as a positive control formRNA EpoR expression. RESULTS.: VSMC growth index of SHR was enhanced up to 1.6-fold by rHuEpoconcentrations of 16 U/ml or more, in the presence of 1% fetalcalf serum. No such stimulation was observed in VSMC of WKY.Binding studies with radiolabelled rHuEpo showed either extremelylow or no specific binding of radio-labelled rHuEpo by VSMC.However, Northern blot analysis revealed the expression of EpoRmRNA in VSMC of either rat strain. CONCLUSION.: The present report provides preliminary evidence in favour ofa direct action of the hormone on vascular smooth muscle viaa specific EpoR.     

Optimal dialysate calcium and vascular calcification.

Sir, Yamada et al. [1] report that the rate of progression of aorticcalcification is related to the increase of serum calcium duringthe haemodialysis session (Ca), using a stepwise multivariateregression     

Parathyroid hormone receptor

Nephrology Dialysis Transplantation 1994; 9: 129–130. P. 594, para. 2, line 6: should read 3p21.1-p22 (Pausova etal., Genomics, 1994; 20:20–26).     

Influence of various calcium intakes on calciuin-oxalate crystalluria in rats on sodium-oxalate diet

Forty adult male Wistar rats were placed in metabolic cageson a Ca-deficient diet (0.1%) for 7 days and then on a Ca-deficient,Na-oxalate (NaOx) enriched diet (20 mg/100 g) for another 14days. The animaLs were subdivided into three groups receivingthree different types of mineral water: group I (n=13), Badoit(Ca 222 mg/i); group II (n=14), Contrexéville (Ca 467mg/l);and group III (n=13), Evian (Ca 78 mg/l). Another series of25 rats (group I, n=9; group II, n=8; group III, n=8) underwentthe same study protocol, except that they received a normalCa diet (1%). On the low-Ca diet, urinary Ca-Ox monohydrate(COM) crystals were observed only under the Na-Ox diet, witha mean crystal number significantly greater in group III (16.7±4.5crystals/mm ) than in group I or II rats (2.5 ± 1.5 or4.1 ± 1.5 crystals/mm respectively). Urinary Ca concentrationsdecreased in all groups (/<0.001) under the Na-Ox diet, whileurinary oxalate concentrations increased in all groups (P<0.001).On the normal Ca diet, COM crystal excretion was observed onlywith the Na-Ox-enriched diet, but in this case feeding the Na-Oxdiet did not modify urinary oxalate excretion. Ca/Ox ratio wassignificantly lower under 0.1% Ca diet than under normal Cadiet, related with the type and the number of crystals observed,demonstrating that assessment of crystalluria can provide anindex of disease severity. Moreover, the hardness of the drinkingwater influ ences urinary COM crystal excretion only under alow-Ca, oxalate-rich diet, suggesting that the total calciumintake rather than the water calcium content is an importantfactor in the occurrence of Ca-Ox nephrolithiasis.     

Aluminium-related osteodystrophy and desferrioxamine treatment: role of phosphorus

We investigated (1) the prevalence of aluminium overload among96 patients with symptomatic bone disease haemodialysed from1987 to 1989 in the Sao Paulo area, Brazil; (2) the effect of6 months desferrioxamine (DFO) treatment (1–2 g/week).All patients underwent a first bone biopsy. Aluminium overload(extent of stainable bone aluminium more than 20% trabecularsurface) was observed in 74 of 96 patients. Forty overloadedpatients were divided into patients with high bone formationrate (BFR) (group 1; n=17) and patients with low BFR (group2; n=23), and had a second biopsy after DFO therapy. In bothgroups aluminium surface was reduced after treatment (P<0.001),osteoblast surface (P<0.02-P<0.01) and plasma parathyroidhormone (iPTH) (P<0.01) increased. In group 1 BFR remainedhigh. In group 2 BFR remained low in 16 patients (2a) and increasedin seven (P<0.02) (2b). In group 2a plasma phosphorus wasbelow that in group 2b patients, before (P<0.03) and after(P<0.01) DFO. The histological features of group 2a patientsresembled hypophos-phataemic osteomalacia, those of group 2bpatients aluminium osteodystrophy. These data show a high prevalence of aluminium overload in Brazilianpatients. Low-dose DFO therapy was safe, decreased bone pain,prevented fractures, and reduced stainable bone aluminium. Bonelesions only partially improved, suggesting that low phosphorusintake and/or plasma calcitriol concentrations may have preventedimprovement of bone formation and mineralization.     

Dietary salt restriction accelerates atherosclerosis in apolipoprotein E-deficient mice

BACKGROUND: Whether a general reduction in salt intake reduces or actually enhances cardiovascular mortality in man remains an issue of controversy. Low sodium diets may lead to adverse side effects by stimulating the renin-angiotensin and sympathetic nervous systems. The present study was designed to investigate the effects of low dietary salt on atherosclerotic lesion progression in apolipoprotein E deficient (apoE(-/-)) mice. METHODS AND RESULTS: We fed 7-week-old apoE(-/-) mice on low (0.036% NaCl; n=28) or regular (0.64% NaCl; n=26) salt diets for 16 weeks. At the age of 23 weeks, the cross-section surface area of atherosclerotic plaques was measured in aortic root and thoracic aorta. Serum total cholesterol, triglycerides, plasma angiotensin levels and urinary protein/creatinine concentrations were assessed. Exposure to low salt caused significant increases in atherosclerotic lesion surface area in thoracic aorta, but did not alter lesion area in aortic root. Low-salt mice also had higher serum total cholesterol and higher plasma angiotensin II (ANG-II) concentrations. Atherosclerotic lesion area was correlated with ANG-II levels in low-salt but not in regular-salt animals, and with total cholesterol concentration in all mice. Mean arterial pressure was comparable in both groups. CONCLUSIONS: Dietary salt restriction accelerated atherosclerotic lesion formation in apoE(-/-) mice through a mechanism that is probably related to ANG-II formation. Whether these findings are relevant to human cardiovascular disease remains to be evaluated.     

Vascular changes in hemodialysis patients in response to recombinant human erythropoietin

The partial correction of anemia with recombinant human erythropoietin (rHuEpo) is frequently associated with an increase in arterial pressure and could oppose the beneficial effect of anemia correction on myocardial function. In order to analyze the influence of rHuEpo therapy on the vessels and the heart, we performed systemic and regional hemodynamics studies in 11 hemodialysis patients before and 10 to 35 weeks after initiation of rHuEpo therapy, when hemoglobin concentration was 6.8 +/- 0.9 and 10.6 +/- 0.66 g/dl (mean +/- SD), respectively. The mean arterial pressure remained unchanged during this period (88 +/- 21 vs. 88 +/- 15 mm Hg). Echocardiographic study showed that rHuEpo treatment led to a decrease in left ventricular end-diastolic diameter (4.9 +/- 0.5 vs. 5.1 +/- 0.6 cm; P less than 0.03), left atrial diameter (3.22 +/- 0.30 vs. 3.43 +/- 0.33; P less than 0.03), and left ventricular mass index (109.8 +/- 30.6 vs. 133 +/- 30.8 g/m2; P less than 0.05). Left ventricular ejection volume decreased from 86 +/- 24 to 75 +/- 19 ml (P less than 0.03) and heart rate from 76 +/- 9 to 70 +/- 10 beats/min (P less than 0.05). Cardiac index decreased from 4715 +/- 700 to 3635 +/- 444 ml/min/m2 (P less than 0.01) and peripheral resistances rose from 1480 +/- 162 to 1943 +/- 250 dynes.sec.cm-5.m2 (P less than 0.01). Fractional ejection and mean circumferential fiber shortening remained unchanged. The treatment with rHuEpo did not change the aortic diameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brenner & Rector's The Kidney. 7th edition by Barry M. Brenner

The first edition of this highly esteemed textbook of nephrologydates back to 1976. Regular updates have taken into accountthe steady, remarkable progress made in this discipline of internalmedicine in the last quarter of the 20th century. The most recent,7th edition has became available this year. As previously, itlargely reflects the advances of the last few years and presentsthe state of the art in the field of interest.