Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum cystyl aminopeptidase (CAS) activity was estimated at 36 weeks' gestation in 209 normotensive pregnancies. The highest activity was found in 31 women who had spontaneous deliveries before 38 weeks' gestation and the lowest in 76 women who were induced after term. The enzyme levels in 117 women who developed hypertension of pregnancy were higher than for normotensives; the highest levels were found in 32 women with pre-eclampsia. A correlation was found between serum CAS activity at 36 weeks' gestation and the birth weight of babies of women who went into spontaneous labour at term (277 to 283 days' gestation).
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PMID:Serum cystyl aminopeptidase activity in the 36th week of pregnancy. 44 65

A variety of tubular marker proteins, as compared to healthy controls, are excreted at an increased rate in the urine of patients with renal damage. Beside cytoplasmic glutathione-S-transferase and lysosomal beta-N-acetyl-glucosaminidase (beta-NAG) the majority of kidney-related urine proteins derives from membrane surface components of the most vulnerable proximal tubule epithelia, among them ala-(leu-gly)-aminopeptidase, gamma-glutamyl transpeptidase (GGT), the tubular portion of angiotensinase A, the major brush border glycoprotein 'SGP-240' and adenosine-deaminase-binding protein. Urinary tissue proteins, e.g. brush border (BB) microvilli, are immunologically identical with those antigens prepared from cell membranes of the human kidney itself. BB antigens are shed into the urine of patients with glomerulonephritis, interstitial nephritis, systemic diseases, e.g. systemic lupus erythematosus (SLE), diabetes mellitus and multiple myeloma, arterial hypertension, infectious diseases (malaria, AIDS) and after operations, renal grafting and administration of X-ray contrast media, aminoglycosides or certain cytostatics (cis-platinum). Tissue proteinuria of tubular proteins is determined by enzyme-kinetic or quantitative immunological assays applying either poly- or monoclonal antikidney antibodies. Clinical, ultrastructural and histochemical studies support the idea that both 'soluble' and high-molecular-weight membrane particles (vacuolar blebs, greater than 10(6) dalton) as well as microfilamental components of the epithelial cytoskeleton contribute to tubular 'histuria' which appears as a sensitive parameter in monitoring tubular damage under clinical conditions at a very early phase.
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PMID:Urinary proteins of tubular origin: basic immunochemical and clinical aspects. 225 76

Excretion patterns of kidney related urinary proteins such as lysosomal beta-N-acetylglucosaminidase (beta NAG), brush-border Ala-(Leu-Gly)-aminopeptidase (AAP), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (AP) as well as of IgG, albumin, and alpha-1-microglobulin, were assessed in patients with chronic glomerulonephritis (n = 53), pyelonephritis (n = 27), systemic lupus erythematodes (n = 5), and patients with essential arterial hypertension (n = 18). Excretion of tubular marker enzymes and serumproteins (related to urine creatinine concentration = protein creatinine index) in spontaneously voided second morning urine was significantly higher as compared to the controls (n = 2). Alpha-1-microglobulin was markedly elevated in both pyelonephritis and glomerulonephritis indicating disturbance in tubulointerstitial handling of microglobulins also in cases with primary glomerulopathy. Rise of albumin, IgG, and alpha-1-microglobulin as well as of tubular kidney markers AAP, AP, GGT, and beta NAG in cases with arterial hypertension without preexisting nephropathy support the hypothesis of a defect in charge and size permselectivity in these patients which is probably due to an increase in glomerular capillary perfusion pressure and hyperfiltration.
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PMID:Kidney- and serum derived proteins in urine of patients suffering from renal diseases or arterial hypertension. 247 9

alpha-Human atrial natriuretic peptide (hANP) is secreted by the heart and acts on the kidney to promote a strong diuresis and natriuresis. In vivo it has been shown to be catabolized partly by the kidney. Crude microvillar membranes of human kidney degrade 125I-ANP at several internal bonds generating metabolites among which the C-terminal fragments were identified. Formation of the C-terminal tripeptide was blocked by phosphoramidon, indicating the involvement of endopeptidase-24.11 in this cleavage. Subsequent cleavages by aminopeptidase(s) yielded the C-terminal dipeptide and free tyrosine. Using purified endopeptidase 24.11, we identified seven sites of hydrolysis in unlabelled alpha-hANP: the bonds Arg-4-Ser-5, Cys-7-Phe-8, Arg-11-Met-12, Arg-14-Ile-15, Gly-16-Ala-17, Gly-20-Leu-21 and Ser-25-Phe-26. However, the bonds Gly-16-Ala-17 and Arg-4-Ser-5 did not fulfil the known specificity requirements of the enzyme. Cleavage at the Gly-16-Ala-17 bond was previously observed by Stephenson & Kenny [(1987) Biochem. J. 243, 183-187], but this is the first report of an Arg-Ser bond cleavage by this enzyme. Initial attack of alpha-hANP by endopeptidase-24.11 took place at a bond within the disulphide-linked loop and produced a peptide having the same amino acid composition as intact ANP. The bond cleaved in this metabolite was determined as the Cys-7-Phe-8 bond. Determination of all the bonds cleaved in alpha-hANP by endopeptidase-24.11 should prove useful for the design of more stable analogues, which could have therapeutic uses in hypertension.
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PMID:Hydrolysis of alpha-human atrial natriuretic peptide in vitro by human kidney membranes and purified endopeptidase-24.11. Evidence for a novel cleavage site. 297 76

Ninety-two primigravidas were screened biweekly by measurement of plasma cystyl aminopeptidase from 28 weeks' gestation until delivery. Fourteen developed hypertension with or without proteinuria after 36 weeks. The hypertensive group had significantly higher levels of the enzyme at 30 weeks, although this difference was not significant at 34 weeks. The rise in the hypertensive group was less than 50% between weeks 30-34 in all cases, whereas it was over 50% in all but two of the 43 controls. The difference in the rates of increase of the enzyme and its action on antidiuretic hormone may have some bearing on the subsequent development of hypertension.
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PMID:Change in plasma cystyl aminopeptidase (oxytocinase) between 30-34 weeks' gestation as a predictor of pregnancy-induced hypertension. 318 91

Intracarotid (IC) injection of bestatin produced a dose-dependent biphasic change in blood pressure (BP) of the rat, consisting of an initial short-lasting fall followed by a long-lasting increase. This effect was regularly depressed or abolished by IV injection of naloxone. IC injection of Leu-enkephalin also produced a biphasic BP response, with the same characteristics as that produced by IC injection of bestatin. This effect was also easily blocked by IV injection of naloxone. IC injection of bestatin significantly potentiated the BP response to IC injection of Leu-enkephalin. This potentiated response was blocked by naloxone. IC injection of both bestatin and phosphoramidon, whether separately or in combination, significantly depressed the hypertensive response to physostigmine. This depressive action of bestatin and phosphoramidon on physostigmine hypertension can be significantly antagonized or even reversed by IV injection of naloxone. IC injection of both bestatin and phosphoramidon did not affect the BP response to either acetylcholine or catecholamines. It is concluded that bestatin and phosphoramidon, injected into the carotid artery, inhibit the activity of aminopeptidase and "enkephalinase", thus producing an accumulation of enkephalins in the central nervous system. These enkephalins activate opioidergic receptors in the brain, but concomitantly produce a depression of the cholinergic-adrenergic interaction in the central nervous system, which is known to be a prerequisite for the hypertensive response to physostigmine in the rat.
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PMID:Effects of bestatin and phosphoramidon on the hypertensive response to physostigmine in the rat. 344 23

The effect of acute intracerebroventricular (i.c.v.) injections of angiotensin II and III (ANG II and ANG III; 0, 1, 10 and 100 pmol in 2 microliters artificial cerebrospinal fluid (CSF) on blood pressure and water consumption was investigated in Okamoto-Aoki spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive controls. Heightened sensitivity to i.c.v. ANG II and ANG III was observed in the SHR compared with the WKY and SD strains (P less than 0.001), for both pressor and drinking responses. In addition, i.c.v. treatment with an aminopeptidase B inhibitor, bestatin (20 nmol in 1 microliter artificial CSF) significantly potentiated the heightened pressor response to i.c.v.-injected ANG II and ANG III (100 pmol) in SHR and to a lesser degree in WKY animals compared with SD controls (P less than 0.001). These results suggest that a dysfunction in central aminopeptidase activity results in an extended life of endogenous angiotensins, and perhaps other peptides that may contribute to the high blood pressure seen in this animal model of human essential hypertension.
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PMID:Heightened pressor effect and dipsogenicity to intracerebroventricularly applied angiotensin II and III in spontaneously hypertensive rats. 347 26

The particulate enzyme that degrades angiotensin I (ANG I) to [des-aspartate1]angiotensin I ([des-Asp1]ANG I) in the hypothalamic homogenate of the rat has been established as a specific aminopeptidase. The major characteristics is its resistance to inhibition by 10(-4) M amastatin, bestatin and EDTA. Among the four amino acyl-beta-naphthylamides (aspartyl, glutamyl-, arginyl- and leucyl-beta-naphthylamide), aspartyl-beta-naphthylamide is the most susceptible substrate of the enzyme; being degraded at twice the rate of arginyl-, and leucyl-beta-naphthylamide, and six times that of glutamyl-beta-naphthylamide. Although the precise role of this aminopeptidase has yet to be determined, its presence establishes the existence of a specific pathway for the degradation of ANG I that bypasses the formation of ANG II. The relationship between degradation and hypertension is shown by our recent findings that the formation of [des-Asp1]ANG I form ANG I in the hypothalamic homogenate of the spontaneously hypertensive rat (SHR) is significantly enhanced, and the findings of other investigators that the production of ANG II by neuronal cultures of the SHR is significantly decreased.
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PMID:Degradation of angiotensin I to [des-Asp1]angiotensin I by a novel aminopeptidase in the rat hypothalamus. 809 92

Rats of the Milan Hypertensive Strain (MHS) may be considered a useful model for understanding the genetic molecular mechanism underlying a primary form of hypertension in at least a subgroup of patients. Many differences between MHS and its normotensive control strain (MNS) were found at the organ, cellular and biochemical level. In the present investigation renal cell membrane proteins (BBMV) were analysed by two-dimensional electrophoresis and a difference between MHS and MNS was shown in a polypeptide of 32 kDa, subsequently identified as the C-terminal fragment of aminopeptidase M (APM). The activity of the enzyme was higher in MHS. Genetic relationships between this enzyme and the other biochemical cellular abnormalities of MHS, namely sodium transport in BBMV and renin activity in kidney cortex were investigated in MHS, MNS and in two inbred recombinant strains. This analysis showed that faster sodium transport, low kidney levels of renin and hypertension, but not differences in two-dimensional electrophoretic pattern and in aminopeptidase M activity, cosegregated in recombinant strains. These results are consistent with the hypothesis that the faster sodium transport can be considered a primary cellular abnormality responsible for hypertension in MHS and that the aminopeptidase difference is not involved in the cellular abnormalities.
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PMID:Relationships among alterations in renal membrane sodium transport, renin and aminopeptidase M activities in genetic hypertension. 810 53

In most cases of glomerulonephritis (GN) long-term course lead to chronic renal failure. The cause of inevitably gradually progress of GN to end-stage renal disease (ESRD) is unclear. The histological abnormalities seen in patients with progressive renal failure consist of focal and segmental glomerulosclerosis and tubulointerstitial nephritis. At present it is considered that tubulointerstitial changes attends almost all forms of progressive glomerular and vascular injury. It was known that chronic tubulointerstitial nephritis is characterized morphologically by tubular atrophy, interstitial fibrosis and interstitial inflammation of variable severity. The pathomechanism of this changes is complicated. Tubular ischaemia results from obliteration of peritubular capillaries, adaptation of tubular function with increased oxygen consumption and increased glomerular capillary permeability to macromolecules are reasons of chronic tubular damage. Injured tubules release growth factors and cytokines, which induce interstitial fibroblast proliferation, chemo-attraction and proliferation of infiltrating cells, and disruption of the balance between synthesis and degradation of cellular constituents. The consequences of these processes are tubular atrophy and interstitial fibrosis. Because of many studies concurred that tubulointerstitial changes determinant the progression of GN, tubular injury markers were searched for. Although over 50 enzymes were detected in human urine, only a few have been used for diagnosis in renal disease. The most widely used are lysosomal enzyme N acetyl-beta-D-glucosaminidase (NAG) and brush border enzymes alanine-aminopeptidase (AAP) and gamma-glutamyltransferase (GGT). tubular damage in hypertension, diabetes and in diagnostics of renal disease. AAP and GGT, brush border enzymes seem to be sensitive markers of renal injury too. Pathological value of GGT was observed even in the early stage of disease. Measurement of urinary excretion of low molecular weight proteins was valuable supplement in estimation of tubulointerstitial system malfunction. These proteins are readily filtered by normal glomeruli and virtually completely reabsorbed by normal proximal tubules. Favour are alpha-1-microglobulin (alpha-1-m) and retinol-binding protein (RBP) because they are less affected than beta-2-microglobulin (beta-2-m) by low urine pH. Above presented review confirm that further research in correlation between activity of disease, histological picture, deterioration in renal function and changes in urinary excretion of markers proteins (for example alpha-1-m, AAP, NAG, GGT) is advisable, and can contribute to use in clinic diagnostics of GN.
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PMID:[The role of tubulointerstitial changes in progression of kidney function failure in patients with chronic glomerulonephritis (GN)]. 875 11


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