Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tubular overwork is thought to be a promoter of the tubular hypertrophy and renal failure that occur in response to renal mass reduction. Because Na-K-adenosinetriphosphatase (Na-K-ATPase) is an index of tubular work, we evaluated the effects of subtotal nephrectomy and of enalapril therapy, which delays the evolution of renal lesions, on tubular hypertrophy and Na-K-ATPase activity along the rat nephron. Within 6 wk, 70% reduction of renal mass engendered hypertrophy of the proximal convoluted tubule (PCT), thick ascending limb (TAL), and collecting duct (CD), as well as parallel increments in Na-K-ATPase activity per millimeter tubule length (Na-K-ATPase activity per unit surface area was not modified by subtotal nephrectomy). Chronic enalapril therapy prevented part of the hypertrophy (but not Na-K-ATPase stimulation) of the PCT and the whole stimulation of Na-K-ATPase (but not hypertrophy) in the CD, whereas it had no effect on the TAL. Enalapril effect on Na-K-ATPase in CD might result from reduced bradykinin metabolism, as the reduction in urinary excretion of bradykinin observed in subtotally nephrectomized rats was prevented by enalapril therapy.
 ...
PMID:Na-K-ATPase along rat nephron after subtotal nephrectomy: effect of enalapril. 876 19

We have isolated a labile, specific sodium pump inhibitor or digitalis-like factor from the peritoneal dialysate of volume-expanded renal failure patients whose levels correlated closely with volume status and blood pressure. This study characterizes the inhibitory profile of this agent compared with that of ouabain against the three alpha-isoforms of the sodium pump. We prepared microsomal Na,K-ATPase from rat tissues representing the highest proportion of one of the alpha-isoforms. Both Northern and Western blot analyses confirmed that kidney had predominantly the alpha1-isoform, skeletal muscle the alpha2-isoform, and fetal brain the alpha3-isoform. Ouabain (5 x 10(-6) mol/L) produced little inhibition of kidney Na,K-ATPase (3.4+/-2.0%) but significant inhibition of skeletal muscle (37.2+/-3.7%, P<.001) and fetal brain (38.8+/-3.5%, P<.001) activity. In contrast, the labile digitalis-like factor, causing comparable inhibition of fetal brain Na,K-ATPase activity (33.3+/-4.7%), produced markedly greater inhibition of kidney (42.5+/-5.6%, P<.001) and moderately greater inhibition of skeletal muscle pump activity (57.7+/-6.3%, P<.05). In addition, the labile digitalis-like factor produced a marked concentration-dependent inhibition of the alpha2- and alpha3-isoforms (r=.79, P=.00005). Experiments combining the labile digitalis-like factor and ouabain confirmed that digitalis-like factor, unlike ouabain, was an effective inhibitor of all three isoforms in rat, in particular alpha2. The different pattern of isoform sensitivity displayed by the labile digitalis-like factor and ouabain further differentiates the two agents and raises some interesting possibilities about the functional implications of the endogenous factor.
 ...
PMID:Sodium pump isoform specificity for the digitalis-like factor isolated from human peritoneal dialysate. 936 92

Looking for causes or consequences of primary hypertension much attention is drawn to the ion transport systems of the cellular membrane. The existence of endogeneous digitalis-like factors, that lower the activity of Na+/K(+)-ATPase and result in a complex change of electrolyte balance of cells are discussed as a reaction of the organism to salt and volume retention. The measurement of passive permeability of erythrocyte membranes for potassium is an easy and useful method for the detection of disturbances of Na+/K(+)-transport, especially for extensive screening investigations. We examined the potassium permeability of erythrocytes in healthy individuals (GR1, n = 48), patients with compensated renal insufficiency (GR2, n = 36) and diabetics (GR3, n = 25) as well as a group of diabetics with renal failure (GR4, n = 47). The relative change of potassium concentration in the whole blood, based on the efflux of potassium during a 4-hour-incubation at 37 degrees C, is defined as a measure for K(+)-permeability. K(+)-concentrations are determined every 60 minutes with ion sensitive electrodes. K(+)-permeability was significantly increased in patients with compensated renal insufficiency compared to the control group and to diabetics. Diabetics differed markedly in their erythrocyte reaction regarding K(+)-permeability. Whereas patients with renal insufficiency show an efflux of potassium during investigation there is a decrease of potassium in plasma in diabetics. The K(+)-permeability results of patients with both diseases are intermediate between the GR2- and GR3 results and are significantly different from the control group. When g-strophanthin is added to inhibit the sodium pump, the differences between the groups are abolished. The decreased K+permeability in diabetics compared to the control group could be explained by the increased supply of energy-rich substrates for the Na+/K(+)-ATPase.
 ...
PMID:K(+)-permeability in diabetics and nondiabetics with and without renal insufficiency. 928 37

The activity of the plasma membrane Ca2+ ATPase of chronic renal failure patients is decreased by circulating inhibitors yet to be characterized. In this study, inhibitors of Ca2+ ATPase were isolated from ultrafiltrate of patients with end-stage renal failure. They were identified as dimethylguanosine, phenylethylamine, and phenylacetic acid by chromatography and mass spectrometry. Ca2+ ATPase activity was measured spectrophotometrically as the difference in hydrolysis of ATP in the presence and absence of Ca2+ with different concentrations of ATP and the isolated substances. All of the identified compounds are sufficiently lipophilic to penetrate the blood-brain barrier and to accumulate in cerebral tissue. The inhibitory effects of these agents were additive. The apparent K(m) values for ATP and Ca2+ were not altered by these substances, suggesting a noncompetitive mechanism of inhibition. In plasma of healthy subjects, the substances were not detectable. The Ca2+ ATPase inhibitors identified may play a role in the pathophysiology of end-stage renal failure and, potentially, in monitoring toxic effects on cellular Ca2+ metabolism in renal failure.
 ...
PMID:Characterization of dimethylguanosine, phenylethylamine, and phenylacetic acid as inhibitors of Ca2+ ATPase in end-stage renal failure. 964 35

The renal functional changes following infusion of dopamine are well documented. The most pronounced effect is the increase in renal blood flow and a marked natriuretic response. Due to its specific renal effects, dopamine has become one of the most frequently used drugs in the treatment of critically ill patients with low cardiac output states and/or acute oliguric renal failure. Pharmacological effects of dopamine are dose dependent. Low doses of dopamine predominantly stimulate dopaminergic receptors, but with increasing doses actions secondary to stimulation of adrenergic beta(1) and alpha receptors also appear. Dopamine receptors are classified into the D1 and the D2 subtype families. Stimulation of D1 receptors increases adenylate cyclase activity and intracellular levels of cAMP, whereas D2 receptor activation decrease or do not change adenylate cyclase activity. In the kidney, dopamine receptors have been localized in the renal vasculature except in glomeruli and in the tubules (the proximal tubule > macula densa > the loop of Henle > the distal tubule > collecting ducts). The postsynaptic D1 receptor mediates vasodilation by a direct mechanism, whereas the presynaptic D2 receptor indirectly may dilate the vessels by inhibition of norepinephrine release. Consistent with previous results in animals, the present haemodynamic studies revealed that dopamine in normal subjects elicits a dose dependent biphasic effect on the mean arterial blood pressure. With 1 and 2 micrograms/kg/min, a depressor effect resulted from a decrease in the diastolic pressure, whereas a pressor effect, seen with doses at and above 7.5 micrograms/kg/min, was mainly caused by elevations of the systolic pressure. The studies indicated that the increase in cardiac output at low doses of dopamine is secondary to a decrease in peripheral vascular resistance, independent of effects of beta(1) receptors on cardiac contractility and heart rate. Dose-response studies demonstrated that the dopamine-induced increase in effective renal plasma flow (ERPF) reaches its maximum at 3 micrograms/kg/min. The increase in ERPF remained unchanged by pretreatment with metoprolol, and a comparison of dopamine and dobutamine in doses producing similar increases in cardiac output demonstrated that only dopamine increased ERPF. These findings indicate that indirect haemodynamic effects secondary to increases in cardiac contractility and cardiac output do not contribute significantly to the increase in renal perfusion caused by dopamine. In normal subjects, acute hypoxaemia attenuated the renal vasodilating effect of dopamine. The well known natriuretic effect of dopamine was significantly expressed in all of our studies, in which doses ranging from 1 to 5 micrograms/kg/min caused about a two-fold increase in sodium excretion. At doses at and above 7.5 micrograms/kg/min which increased mean arterial pressure, dopamine further increased sodium clearance (CNa) while ERPF was decreasing, indicating the contribution of pressure natriuresis at these high doses. Although not affecting the percentage increase in CNa, metoprolol suppressed the absolute, maximal response to non-pressor doses of dopamine, suggesting that a reduced adrenergic beta(1) receptor activity may indirectly affect the natriuretic response, probably by decreasing renal perfusion pressure. Previous studies in animals demonstrated that dopamine natriuresis can occur independent of increases in ERPF and GFR, and, furthermore, that the response can be abolished by specific D1 receptor antagonists. Evidence obtained by in vitro studies indicated that dopamine via D1 receptors may inhibit the Na(+)-H+ antiport at the brush-border membrane of proximal tubular cells and the Na(+)-K(+)-ATPase activity at basolateral membranes of both the proximal tubule and the medullary thick ascending limb of the loop of Henle. (ABSTRACT TRUNCATED)
 ...
PMID:Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans. 967 40

Endogenous Na, K pump inhibitors may contribute to the pathogenesis of hypertension, and could do so by causing direct vasoconstriction and/or enhancing sensitivity to other vasoconstrictor agents. These effects of the Na, K pump inhibitors are likely due to inhibition of Na-K-ATPase. In turn, cells become depolarized, internal sodium concentration increases and internal calcium is increased by exchange for sodium via the sodium/calcium exchange carrier. This extra calcium is sequestered, increasing the size of the releasable intracellular calcium pool. Both depolarization and the increase in cytosolic calcium can cause vasoconstriction. Both depolarization and the increased size the intracellular calcium pool can sensitize the blood vessel to other vasoconstrictor agents. Endogenous pump inhibitors may also stimulate the release of catecholamines from the intramural sympathetic nerve terminals. Studies of a variety of candidate endogenous Na, K pump inhibitors are reviewed. These include presently unidentified substances extracted from human urine, from peritoneal dialysate of hypertensives with renal failure, and from bovine and rat hypothalamus. Additional candidate compounds include ouabain, selected pregnanes and marinobufagenin, a steroid originally identified in the venom of the frog, Bufo marinus.
 ...
PMID:Summary of studies of changes in vascular reactivity caused by natriuretic hormones. 968 26

Potassium bromate (KBrO3) is known to be an oxidizing agent that is used not only as a food additive, mainly in the bread-making process, but also as a neutralizer in thioglycolate containing hair curling set. Although it has been shown that bromate poisoning could cause severe and irreversible sensorineural hearing loss as well as renal failure, the action mechanism of bromate-induced otoneurotoxicity especially its combination with thioglycolate remains to be studied. In this study, we attempted to investigate the toxic effects of KBrO3 in combination with or without thioglycolate on the auditory brainstem response (ABR) system in the guinea-pigs which was claimed to be very susceptible to the xenobiotics. In a preliminary test, we have found that after consecutive 2 weeks administration, KBrO3 caused a significant prolongation of wave I-III and the interwave latencies of ABR as well as significantly elevated the threshold of hearing, suggesting that the conduction velocity of the peripheral auditory nerve was delayed. By contrast, the absolute latency of wave IV/V and the interwave latency of wave III-V were not significantly prolonged, suggesting that KBrO3 had no effect on the brainstem. This oto-neurotoxic effect of KBrO3 was markedly enhanced by combining with thioglycolate. Our data also indicated that KBrO3 combined with thioglycolate but not KBrO3 alone prominantly caused a decrease of body weight. However, enzymatic activities (including Na+/K+-ATPase and Ca2+-ATPase) and the level of nitric oxide (NO) was significantly affected in the brainstem. Based on these findings, we tentatively conclude that whether KBrO3 alone or KBrO3 combined with thioglycolate induced oto-neurotoxicity majorly through the peripheral auditory nerve rather than via the central brainstem intoxication.
 ...
PMID:The detrimental effects of potassium bromate and thioglycolate on auditory brainstem response of guinea pigs. 1099 99

A sodium pump inhibitor (digitalis-like factor), isolated from the peritoneal dialysate of volume-expanded, hypertensive patients with kidney failure who were treated with this dialysis modality, was further purified and characterized by means of supercritical fluid chromatography, a separation technique whose application to very-low-concentration biomolecules is new. Previous studies suggested that after high-performance liquid chromatography (HPLC) purification, this inhibitor was the only factor correlated with volume status and blood pressure in these patients. When this same HPLC fraction was furthered purified on 2-dimensional supercritical fluid chromatography, a single peak coeluted with [Na,K]ATPase inhibitory activity. When split specimens were used, there was a strict correlation between the peak area, measured by flame ionization detection, and activity (n=10, R=0.98, P=0.00001). Inhibitory activity after supercritical fluid chromatography was still correlated with the degree of volume expansion of donor patients (P=0.01). After HPLC purification, this volume-sensitive inhibitor was chemically labile. With further purification on supercritical fluid chromatography, the active peak was still labile with comparable half-life. Supercritical fluid chromatography coupled with flame ionization detection provided an estimate of the amount of the inhibitor present. Again using split specimens, we determined that the labile digitalis-like factor was approximately 30-fold more effective than ouabain in inhibiting renal [Na,K]ATPase activity and >/=500 times more effective than ouabain in causing vascular smooth muscle contraction. The data suggest that we have purified to homogeneity a labile digitalis-like factor that is readily distinguished from ouabain or bufalin, based on chromatographic characteristics, chemical lability, and a much lower effective concentration for its biological activity.
 ...
PMID:Application of supercritical fluid chromatography to characterize a labile digitalis-like factor. 1111 25

In patients with chronic renal failure (CRF), the reduction of dietary protein intake may correct uremic symptoms, slow the rate of progression of renal failure, and delay the onset on dialysis. Concerns have been made on the nutritional consequences of protein-restricted diets. Over 15 years, 239 patients were treated with a very-low-protein diet providing 0.3 g vegetable protein/kg/day supplemented (SLPD) with essential amino acids and keto analogs. Many adverse consequences of uremia were corrected by this regimen, such as metabolic acidosis, secondary hyperparathyroidism, resistance to insulin, decreased Na(+)-K(+)-ATPase activity. A joint physician-dietitian monitoring contributed to the maintenance or obtention of a satisfactory nutritional status, even in patients at risk, diabetics, patients with the nephrotic syndrome and with renal allograft chronic rejection. The outcome of these patients when treated by hemodialysis or transplantation was favorable, their nutritional status being preserved. Results from the present study and results of other studies show that SLPD can be used in patients with advanced CRF without adverse effects in carefully selected and monitored patients.
 ...
PMID:Are supplemented low-protein diets nutritionally safe? 1115 66

Aberrant gene-environment interactions are implicated in the pathogenesis of congenital renal dysgenesis (CRD), a leading cause of renal failure in infants and children. We have recently developed an animal model of CRD that is caused by gestational salt stress (5% NaCl diet; HS) of bradykinin B2R null mice [B2R(-/-)CRD; El-Dahr SS, Harrison-Bernard LM, Dipp S, Yosipiv IV, and Meleg-Smith S. Physiol Genomics 3: 121-131, 2000.]. Developing B2R(-/-)CRD mice exhibit tubular and glomerular cysts, stromal expansion, and loss of corticomedullary differentiation. In addition, B2R(-/-)CRD mice exhibit transient hypertension from 2 to 4 mo of age. The present study was designed to determine the long-term consequences of CRD on renal morphology and salt sensitivity of blood pressure in B2R(-/-)CRD mice. One-year- and 18-mo-old B2R(-/-)CRD mice exhibited stunted renal growth, glomerular cystic abnormalities, and collecting duct ectasia. Moreover, tumors of mesenchymal cell origin emerged in the dysplastic kidneys of 90% of 1-yr-old and 100% of 18-mo-old B2R(-/-)CRD mice but not in age-matched B2R(-/-) or wild-type mice. When challenged with an HS diet, 18-mo-old B2R(-/-)CRD exhibited a significant rise in systolic and diastolic blood pressures and more pronounced natriuresis and diuresis compared with salt-loaded 18-mo-old wild-type mice. Kidney aquaporin-2 expression was decreased by 50%, whereas renin, ANG type 1 receptor, and Na+-K+-ATPase levels were not different in B2R(-/-)CRD mice compared with controls. In conclusion, this study demonstrates that B2R(-/-)CRD mice exhibit permanent phenotypic and functional abnormalities in renal growth and differentiation. This novel model of human disease links gene-environment interactions with renal development and blood pressure homeostasis.
 ...
PMID:Renal and blood pressure phenotype in 18-mo-old bradykinin B2R(-/-)CRD mice. 1280 91


<< Previous 1 2 3 4 5 6 7 8 9 Next >>