In-vivo induction of monocyte chemotactic and activating factor in patients with chronic renal failure

SummaryThe formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the micro vasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1α (6-keto-PGF1α) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the a-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is - at least partially - due to an acquired defect of the platelet a-granule release and an increased generation of PGI2 in the micro vasculature.

Download Full-text

Endogenous vasopressin regulates Na-K-ATPase and Na+-K+-Cl− cotransporterrbsc-1 in rat outer medulla

AJP Renal Physiology ◽

10.1152/ajprenal.00354.2000 ◽

2002 ◽

Vol 282 (2) ◽

pp. F265-F270 ◽

Cited By ~ 11

Author(s):

Claudia A. Bertuccio ◽

Fernando R. Ibarra ◽

Jorge E. Toledo ◽

Elvira E. Arrizurieta ◽

Rodolfo S. Martin

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Atpase Activity ◽

Receptor Antagonist ◽

The Other ◽

Outer Medulla ◽

Physiological Conditions ◽

Increased Activity ◽

Expression And Activity

Previous reports have shown a stimulatory effect of vasopressin (VP) on Na-K-ATPase and rBSC-1 expression and activity. Whether these VP-dependent mechanisms are operating in vivo in physiological conditions as well as in chronic renal failure (CRF) has been less well studied. We measured ATPase expression and activity and rBSC-1 expression in the outer medulla of controls and moderate CRF rats both before and under in vivo inhibition of VP by OPC-31260, a selective V2-receptor antagonist. OPC-31260 decreased Na-K-ATPase activity from 11.2 ± 1.5 to 3.7 ± 0.8 in controls ( P < 0.05) and from 19.0 ± 0.8 to 2.9 ± 0.5 μmol Pi · mg protein−1 · h−1 in moderate CRF rats ( P < 0.05). CRF was associated with a significant increase in Na-K-ATPase activity ( P < 0.05). Similarly, CRF was also associated with a significant increase in Na-K-ATPase expression to 164.4 ± 21.5% compared with controls ( P < 0.05), and OPC-31260 decreased Na-K-ATPase expression in both controls and CRF rats to 57.6 ± 9.5 and 105.3 ± 10.9%, respectively ( P < 0.05). On the other hand, OPC-31260 decreased rBSC-I expression in both controls and CRF rats to 60.8 ± 6.5 and 30.0 ± 6.9%, respectively ( P < 0.05), and was not influenced by CRF (95.7 ± 5.2%). We conclude that 1) endogenous VP modulated Na-K-ATPase and rBSC-1 in both controls and CRF; and 2) CRF was associated with increased activity and expression of the Na-K-ATPase in the outer medulla, in contrast to the unaltered expression of the rBSC-1. The data suggest that endogenous VP could participate in the regulation of electrolyte transport at the level of the outer medulla.

Download Full-text

Increased Inward Passive Permeability in Vitro to Sodium in Uraemic Erythrocytes

Clinical Science ◽

10.1042/cs0900003 ◽

1996 ◽

Vol 90 (1) ◽

pp. 3-8 ◽

Cited By ~ 2

Author(s):

Dalila B. Corry ◽

Charma C. Ellis ◽

Michael L. Tuck

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Cytosolic Calcium ◽

Na Efflux ◽

The Mean ◽

86Rb Influx ◽

Cell Defect ◽

External K

1. We have reported a normal sodium (Na) pump, but decreased loop-diuretic-sensitive Na efflux in erythrocytes from patients with chronic renal failure on haemodialysis, suggesting a different mode of co-transport in uraemia. 2. The present work extends these findings and examines in vitro simultaneous unidirectional and radiolabelled Na and K fluxes through the Na/K/Cl co-transport and the Na/K pump in washed erythrocytes from seven subjects with chronic renal failure and seven controls. Erythrocyte cytosolic calcium was also examined. 3. Ouabain-sensitive 86Rb influx was similar in patients and controls (1.76 ± 0.19 versus 1.72 ± 0.13 mmol h−1 litre−1 of erythrocytes) as was ouabain-sensitive 22Na efflux (3.62 ± 0.36 versus 4.04 ± 0.39 mmol h−1 litre−1 of erythrocytes). 4. Bumetanide-sensitive 86Rb and 22Na influx and 22Na efflux were measured at three concentrations (4, 8 and 12 mmol/l) of external K. In chronic renal failure, mean bumetanide-sensitive 22Na efflux was decreased at all external K concentrations compared with controls, and at physiological concentrations (4 mmol/l) external K was lower than controls (0.14 ± 0.01 versus 0.38 ± 0.05 mmol h−1 litre−1 of erythrocytes, P < 0.01). Mean bumetanide-sensitive 86Rb influx was also reduced in chronic renal failure at all external K concentrations, and at 4 mmol/l external K was lower than controls (0.13 ± 0.04 versus 0.34 ± 0.04 mmol h−1 litre−1 of erythrocytes, P < 0.01). Conversely, bumetanide-sensitive 22Na influx was markedly increased at all external K levels in chronic renal failure, and at 4 mmol/l external K values were elevated compared with controls (0.64 ± 0.18 versus 0.34 ± 0.04 mmol h−1 litre−1 of erythrocytes, P < 0.001). The mean cytosolic calcium concentration was higher in erythrocytes in chronic renal failure than controls (134.4 ± 8.6 versus 63.7 ± 5.8 nmol/l, P < 0.001). 5. Thus, in washed erythrocytes incubated in artificial media there is a markedly increased ouabain-insensitive Na influx in subjects with chronic renal failure which might be explained in part by the higher levels of cytosolic calcium. In vivo, this cell defect combined with suppression of the Na/K pump could lead to intracellular Na accumulation and play a role in uraemic complications.

Download Full-text

Role of nitric oxide resistance in erythropoietin-induced hypertension in rats with chronic renal failure

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.271.1.e113 ◽

1996 ◽

Vol 271 (1) ◽

pp. E113-E122 ◽

Cited By ~ 11

Author(s):

N. D. Vaziri ◽

X. J. Zhou ◽

F. Naqvi ◽

J. Smith ◽

F. Oveisi ◽

...

Keyword(s):

Nitric Oxide ◽

Renal Failure ◽

Chronic Renal Failure ◽

Angiotensin Ii ◽

Pressor Response ◽

Magnesium Concentration ◽

Induced Hypertension ◽

Group A

We studied the mechanism of erythropoietin (EPO)-induced hypertension (HTN) in rats with chronic renal failure (CRF). After partial nephrectomy, rats were randomized into four groups. Group A received EPO, 150 U/kg, two times weekly for 6 wk to prevent anemia; group B received placebo injections and became anemic; group C received EPO but was kept anemic by dietary iron deficiency; and group D received placebo and regular transfusions to match hematocrit (Hct) in group A. Blood pressure (BP), Hct, platelet cytosolic calcium ([Ca2+]i) and magnesium concentration, and pressor and vasodilatory responses were determined. By design, Hct in groups A and D were comparable and significantly greater (P < 0.01) than in groups B and C. Despite divergent Hct values, the EPO-treated groups A and C showed a significant rise in BP compared with the placebo-treated groups B and D. HTN occurred whether EPO therapy was begun immediately or 4 wk after nephrectomy. EPO therapy augmented the elevation of basal [Ca2+]i and restored the defective thrombin-mediated rise of platelet [Ca2+]i in CRF animals. EPO therapy did not alter caudal artery contraction in response to either 68 mM K(+)-induced depolarization, angiotensin II or alpha 1-agonist, methoxamine in vitro, or the pressor response to angiotensin II in vivo. However, EPO therapy impaired the hypotensive response to nitric oxide (NO) donors, sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine, and reversed the CRF-induced upregulation of guanosine 3',5'-cyclic monophosphate production by thoracic aorta in vitro. Thus EPO-induced HTN in CRF rats is Hct independent and is associated with and perhaps causally related to increased basal and stimulated [Ca2+]i and impaired vasodilatory response to NO.

Download Full-text

Renal synthesis of arginine in chronic renal failure: In vivo and in vitro studies in rats with 5/6 nephrectomy

Kidney International ◽

10.1038/ki.1993.300 ◽

1993 ◽

Vol 44 (4) ◽

pp. 676-683 ◽

Cited By ~ 37

Author(s):

Nadine Bouby ◽

Christine Hassler ◽

Philippe Parvy ◽

Lise Bankir

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

In Vitro Studies

Download Full-text

IN VITRO ANESTHETIC DEPLUORINATION AND IN VIVO LIVER FUNCTION IN FISCHER 344 RATS WITH CHRONIC RENAL FAILURE

Anesthesiology ◽

10.1097/00000542-198009001-00253 ◽

1980 ◽

Vol 53 (3 Suppl) ◽

pp. S253-S253 ◽

Cited By ~ 3

Author(s):

S. A. Rice ◽

T. S. Sievenpiper ◽

R. I. Mazze

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Liver Function ◽

Fischer 344 Rats ◽

Fischer 344

Download Full-text

Cation transport abnormalities in vivo in untreated essential hypertension

Clinical Science ◽

10.1042/cs0700611 ◽

1986 ◽

Vol 70 (6) ◽

pp. 611-616 ◽

Cited By ~ 9

Author(s):

Nicholas A. Boon ◽

Jeffrey K. Aronson ◽

Keith F. Hallis ◽

David G. Grahame-Smith

Keyword(s):

Renal Failure ◽

Essential Hypertension ◽

Chronic Renal Failure ◽

Oral Administration ◽

Matched Control ◽

Cation Transport ◽

Short Term ◽

Sodium Potassium ◽

Digoxin Therapy

1. In order to study cation transport in vivo we have measured the changes in plasma and intra-erythrocytic rubidium concentrations after the oral administration of rubidium chloride. 2. In this paper we describe our findings in 22 patients with untreated essential hypertension, compared with the findings in 22 carefully matched control subjects. Our findings in patients receiving short-term digoxin therapy and in patients with chronic renal failure are also included for comparison. 3. Whereas the findings in patients receiving digoxin and in patients with chronic renal failure are compatible with a widespread reduction in sodium, potassium-ATPase activity in vivo, the findings in patients with untreated essential hypertension are not. 4. Further analysis of the data and a similar study of the disposition of 42K after the intravenous administration of 42KC1 suggest that in vivo net cation transport is enhanced in the erythrocytes of patients with untreated essential hypertension.

Download Full-text

Chronic parathyroid hormone excess in vivo increases resting levels of cytosolic calcium in brain synaptosomes: studies in the presence and absence of chronic renal failure.

Journal of the American Society of Nephrology ◽

10.1681/asn.v1101162 ◽

1991 ◽

Vol 1 (10) ◽

pp. 1162-1168

Author(s):

M Smogorzewski ◽

P Koureta ◽

G Z Fadda ◽

A F Perna ◽

S G Massry

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Chronic Administration ◽

Cytosolic Calcium ◽

Phospholipid Metabolism ◽

Brain Synaptosomes ◽

Presence And Absence

It has been suggested that excess parathyroid hormone (PTH) in chronic renal failure (CRF) or chronic administration of PTH to normal rats caused derangements in norepinephrine and phospholipid metabolism of brain synaptosomes, because of an increase in their resting levels of cytosolic calcium which may induce a decrease in synaptosomal content of ATP. In the study presented here, the resting levels of cytosolic calcium in brain synaptosomes were measured in six groups of rats including: (1) normal rats; (2) rats with CRF of 21-days duration; (3) normocalcemic parathyroidectomized rats with CRF of 21-days duration; (4) rats with CRF of 21-days duration treated with verapamil from day 1 of CRF; (5) normal rats treated with verapamil for 21 days; and (6) normal rats treated with PTH for 21 days. Resting levels of cytosolic calcium of brain synaptosomes of CRF rats (437 +/- 18.0 nM) and normal rats treated with PTH (428 +/- 5.6 nM) were significantly (P less than 0.01) higher than those of normal rats (345 +/- 9.0 nM), normal rats treated with verapamil (354 +/- 8.7 nM), CRF rats treated with verapamil (361 +/- 12.9 nM), or CRF-parathyroidectomized rats (363 +/- 8.2 nM). There were no significant differences between the values of the last three groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

A Method for the Study of Cation Transport in vivo: Effects of Digoxin Administration and of Chronic Renal Failure on the Disposition of An Oral Load of Rubidium Chloride

Clinical Science ◽

10.1042/cs0660569 ◽

1984 ◽

Vol 66 (5) ◽

pp. 569-574 ◽

Cited By ~ 15

Author(s):

N. A. Boon ◽

J. K. Aronson ◽

K. F. Hallis ◽

N. J. White ◽

A. E. G. Raine ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Cation Transport ◽

The Body ◽

Control Group ◽

Loading Dose ◽

Rubidium Chloride ◽

Body Tissues

1. In order to study cation transport in vivo we have measured the changes in plasma and intra-erythrocytic rubidium concentrations following an oral load of rubidium chloride. The changes in plasma rubidium concentration are related to the distribution of rubidium to all the body tissues and the changes in intra-erythrocytic rubidium concentrations provide an example of rubidium uptake by one particular tissue. 2. In eight healthy volunteers pretreatment with a loading dose of digoxin (20 μg/kg) enhanced the rise in plasma rubidium concentrations and attenuated the rise in intra-erythrocytic rubidium concentrations after the oral load of rubidium chloride. 3. Ten patients with chronic renal failure, compared with a well-matched control group, were found to have changes similar to, but more marked than, those caused by digoxin, i.e. a much greater rise in plasma rubidium concentrations and a much smaller rise in intra-erythrocytic rubidium concentrations, after the oral load of rubidium chloride. 4. These findings are consistent with widespread reduction in Na+,K+-ATPase activity in subjects who have taken a loading dose of digoxin and patients with chronic renal failure. They are, therefore, consistent with the findings of previous studies in vitro and show that it is possible to demonstrate changes in cation transport in vivo.

Download Full-text