Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Renal handling of electrolytes, including calcium (Ca), in response to physiological saline infusion (20 mL/kg, i.v., for 2 h) as well as basal circulating levels of Ca-regulating hormones were compared in 27 hypertensive elderly females (mean age 80 +/- 9 years), in 44 normotensive elderly females (79 +/- 9 years) and in 19 young normotensive females (23 +/- 4 years). 2. The hypertensive elderly females showed excessive increase in urine volume and urinary excretions of sodium (Na), Ca and inorganic phosphate (P) in response to saline infusion, associated with slight but significant decrease in circulating levels of Na and ionized Ca compared with those in the other groups. These hypertensive elderly patients also showed characteristic features both in circulating blood pressure and Ca regulating factors; they showed significantly low levels of plasma renin activity and aldosterone concentration, significantly high plasma levels of atrial natriuretic peptide and noradrenalin, compared with those in young controls and normotensive elderly females. 3. Moreover they showed significant increase in basal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D, and significant decrease in basal serum levels of calcitonin, 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D, compared with those in the other groups. 4. These results suggest that the exaggerated natriuresis associated with excessive loss of Ca and P in urine may participate in the abnormality of Ca metabolism in low-renin hypertensive elderly patients.
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PMID:Calcium metabolism in elderly hypertensive patients: possible participation of exaggerated sodium, calcium and phosphate excretion. 183 82

Biologically active 125I-Bolton-Hunter-labeled recombinant human renin (BH-renin) was used to study hepatic processing of renin both in vivo in bile fistula rats and in vitro in isolated perfused rat livers. BH-renin was composed mainly (80%) of a form that bound to concanavalin A-agarose (CB-renin). Twenty minutes after femoral venous injection of CB-renin in vivo, 47% of injected radiolabel was present in liver. Hepatic uptake of CB-renin was inhibited in a dose-dependent manner by mannosylated bovine serum albumin (MBSA) and mannan, but was unaffected by asialofetuin and mannose 6-phosphate. MBSA also significantly inhibited the plasma disappearance of endogenous renin in kidney-ligated rats. Cell separation techniques and light microscopic autoradiography showed that CB-renin was preferentially cleared by hepatic nonparenchymal cells via the mannose receptor, but was also cleared by hepatocytes via an unidentified mechanism. Tissue fractionation demonstrated that after injection of CB-renin, radiolabel was concentrated in lysosome-enriched liver fractions. In the liver, CB-renin was rapidly degraded to trichloroacetic acid-soluble fragments, which accumulated in urine and bile. Leupeptin, an inhibitor of lysosomal proteases, decreased degradation of CB-renin by 60%; vinblastine and colchicine, microtubule binding agents, each inhibited CB-renin degradation by 40%. Our results show that the liver plays a major role in the regulation of plasma renin levels via clearance by the mannose receptor on nonparenchymal cells and subsequent degradation in lysosomes.
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PMID:Hepatic processing of recombinant human renin: mechanisms of uptake and degradation. 187 3

The extracellular and intracellular concentrations of electrolyte were maintained by various systems including kidney and endocrine system. Although concentrations of electrolyte in the extracellular fluid were maintained in normal ranges in healthy elderly subjects, the reserve ability for the maintenance of electrolyte balance decreases with physiological aging. Occurrence of abnormality in electrolyte concentrations in extracellular fluid is thought to be related to pathological aging. The frequency of subjects with abnormal circulating concentrations of electrolytes, as well as abnormal rates of severe such abnormalities increase with age. Clinical characterization and differentiation of physiological and pathological aging are not always easy. On the other hand, the kidney is the central organ for maintenance of electrolyte homeostasis. Decrease in renal ability to retain electrolytes sometimes affect the features of disorders such as hypertension and osteoporosis of elderly subjects. Intravenous infusion of physiological saline at a dose of 20 ml/kg over 2 hr evoked excessive excretion of sodium, calcium and inorganic phosphate in the urine in hypertensive elderly patients and in some patients with senile osteoporosis. These subjects showed decreased levels of plasma renin activity and increased serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. These features indicate that abnormal renal metabolization of electrolytes involving abnormality of endocrine system may be a cause of, and modulate the clinical features of, some disorders of elderly subjects.
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PMID:[Physiological and pathological aging and electrolyte metabolism]. 189 25

Ditekiren is a pseudo-octapeptide being developed as an inhibitor of human renin. Preclinical drug safety studies with this drug involved continuous i.v. infusions through indwelling catheters in the right internal jugular vein of the cynomolgus monkey for up to 30 days. The following physiocochemical properties of ditekiren make it susceptible to intravascular precipitation immediately following iv infusion: (1) the water solubility of ditekiren is high at acidic pH where the drug is formulated (pH 4) but low at physiologic pH, and (2) the water solubility of ditekiren decreases by roughly 50% from room temperature (25 degrees C) to physiologic temperature (37 degrees C). Studies of 28- and 30-day infusion durations revealed intravascular precipitation in monkeys using drug solutions and rates of infusion that were expected to be precipitation-free, based on the solubility of ditekiren and assumptions about blood flow in the monkey right internal jugular vein. Therefore, an in vitro apparatus was used to study the relationship among the drug concentration in the infusate, the rate of infusion, and the occurrence of precipitation in a fluid stream of phosphate-buffered bovine serum albumin solution (a facsimile of plasma). Maximum rates of infusion without precipitation were determined for a range of concentrations of drug in two separate formulations. Infusion conditions identified by the in vitro method as precipitation-free were then tried in a definitive 14-day monkey study. Of 24 monkeys infused with solutions of ditekiren, none showed evidence of intravascular precipitation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Precipitation of the renin inhibitor ditekiren upon i.v. infusion; in vitro studies and their relationship to in vivo precipitation in the cynomolgus monkey. 201 12

Endothelin, a 17-DKa peptide originally described as a potent vasoconstrictor, also stimulates the release of important regulators of glomerular hemodynamics such as atrial natriuretic factor and renin. In the present study we investigated the role of endothelin in the release of another potent vasoconstrictor and mitogen of human mesangial cells, the platelet-derived growth factor. Endothelin stimulated PDGF release at 12 hours and the effect was sustained for 36 hours. This effect was associated with the enhanced induction of mRNAs encoding PDGF A- and B-chain. Endothelin also induced mitogenesis in human mesangial cells which was accompanied by activation of phospholipase C with increased inositol phosphate turnover. These data suggest a mechanism by which endothelin may regulate mesangial cell function in disease states.
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PMID:Endothelin stimulates PDGF secretion in cultured human mesangial cells. 207 61

Conformation of the renin inhibitor peptide, Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys (RIP) has been studied in aqueous solution and in lipid bilayers using 500 MHz 1H NMR spectroscopy. Analysis of the NMR parameters indicates that in aqueous solution, RIP exists as a random coil. On incorporation into lipid bilayers, the peptide adopts a rigid and well defined conformation. The N-terminal end is stabilized by the hydrophobic environment of the lipid bilayer. The C-terminal end is located near the lipid-water interface and attains rigidity due to interaction with the phosphate groups of lipids. The observations emphasize the role of environment in stabilizing significantly different conformations of RIP in three different media--D2O, DMSO and lipid bilayers.
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PMID:Solvent induced conformational changes in renin inhibitor polypeptide. 210 4

Several serum hormone concentrations, enzyme activities, and inorganic phosphate complexes were investigated in 13 hemodialyzed children, 7 kidney-transplanted children, and in 15 healthy controls. Prior to kidney transplantation 10 of the 14 tested hormone levels of hemodialyzed children differed significantly from those of healthy controls; however, after kidney transplantation most of them normalized, only the angiotensin-converting enzyme and alkaline phosphatase activities were significantly elevated in comparison with the control group. Among the different inorganic phosphate complexes, dialysis had the least effect on the CaHPO4 complex. In the hemodialyzed group the plasma renin activities were decreased and the amylase and lipase activities were increased.
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PMID:Hormone, inorganic phosphate concentrations and enzyme activity in hemodialyzed and kidney-transplanted children. 213 65

Renal function was evaluated in six patients with fetal alcohol syndrome (FAS) and eight control subjects before and after fluid restriction and acute acid loading. Baseline serum electrolytes, creatinine clearance, fractional sodium excretion, tubular reabsorption of phosphate, urine and blood pH and osmolalities, plasma renin activity, and plasma aldosterone level were normal in all subjects, but fractional potassium excretion (FEK) was lower in FAS patients than in control subjects (P less than 0.001). Despite equivalent plasma osmolalities (295 +/- 3 vs 293 +/- 2 mosmol/kg, P = 0.2), the maximum urinary osmolality after 12 h of water deprivation in patients with FAS was significantly lower compared with controls (560 +/- 107 vs 965 +/- 77 mosmol/kg; P less than 0.001) and increased to only 578 +/- 101 mosmol/kg after vasopressin administration. After ammonium chloride loading, minimum urine pH was significantly higher in patients than in controls (5.7 +/- 0.17 vs 4.81 +/- 0.19; P less than 0.001). Net acid excretion and FEK were also lower in patients than in controls (102 +/- 11 vs 139.6 +/- 11.3 microEq/min per 1.73 m2 and 23.5 +/- 1.3 vs 29 +/- 1.6%, respectively; P less than 0.001). The data indicate a subclinical renal tubular defect in urine concentration and acidification in patients with FAS.
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PMID:Renal tubular dysfunction in fetal alcohol syndrome. 220 81

The numerous metabolic abnormalities encountered in chronic purgative abusers were investigated and the new concept of autonomous pseudo-Bartter's syndrome documented. Detailed metabolic screening tests were performed in 9 women aged 17-54 years. Two patients underwent further studies, including serum renin and aldosterone, blood volume, total body potassium, urinary chloride and prostaglandin determinations, and each underwent renal biopsy on admission and after 1 year free from laxative abuse. Clinical complications included confusion, convulsions, coma, skeletal muscle weakness with or without paralysis or rhabdomyolysis, cardiac failure, urinary tract infections and bone disease (osteomalacia, secondary hyperparathyroidism and osteoporosis). Hypokalaemia, hypomagnesaemia, hypocalcaemia and hypophosphataemia were frequent findings. Serum creatine kinase correlated inversely with the product of the potassium and serum phosphate (r = -0.86; P less than 0.03), suggesting that hypokalaemia and hypophosphataemia act synergistically to produce muscle damage. After laxative withdrawal, oedema and weight gain, followed by diuresis, ensued in 7 patients. In the other 2, ongoing chloruresis, kaliuresis, hyper-reninaemia and raised urinary prostaglandin secretion persisted. Renal biopsies in these 2 patients showed the features of juxtaglomerular apparatus hyperplasia as well as medullary interstitial cell hyperplasia. In conclusion, pseudo-Bartter's syndrome was documented in 9 chronic laxative abusers. Because patients often indulged in more than one aberrant habit, e.g. laxative and/or diuretic abuse or bulimia, the clinical syndrome produced a myriad of confounding metabolic derangements, which we termed 'metabolic madness'. Laxative withdrawal was complicated by temporary pseudo-idiopathic oedema, which persisted in 2 patients. Further studies in these 2 women strongly supported the concept of 'autonomous pseudo-Bartter's syndrome'.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic laxative abusers with pseudo-idiopathic oedema and autonomous pseudo-Bartter's syndrome. A spectrum of metabolic madness, or new lights on an old disease? 225 4

The effects of angiotensin converting enzyme inhibitors (ACEIs), CGS 14831 (CAS 86541-78-8) and captopril, on the mechanical function and energy metabolism were studied in isolated rat hearts using global ischemia-reperfusion model. The myocardial tissue levels of ATP, creatine phosphate (CP) and pH were determined with 31P-nuclear magnetic resonance (31P-NMR). Global ischemia was induced by cross-clamping of the inflow line for 40 min. While thiol containing ACEI, captopril, significantly inhibited the ATP depletion and pH fall produced by ischemia, non-thiol compound, CGS 14831, did not have any influence on the ATP degradation and pH fall during ischemia. Both CGS 14831 (20 micrograms/ml) and captopril (80 micrograms/ml) have little influence on the mechanical function during the ischemia-reperfusion period. L-Cysteine (44.6 micrograms/ml) inhibited the pH fall significantly during the ischemia without exerting influence on the ATP degradation. These data suggest that local renin-angiotensin-aldosterone system does not play an important role in maintenance of the myocardial mechanical function during ischemia-reperfusion. The thiol residue of captopril is not responsible for the inhibitory effect of this compound on ischemia-induced ATP degradation. Some specific effect of captopril may play a role in the protective effect.
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PMID:Effects of two angiotensin converting enzyme inhibitors on the mechanical function and energy metabolism of isolated rat hearts. A nuclear magnetic resonance study with an active form of benazeprilat and captopril. 229 44


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