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)

Dipeptidyl peptidase IV (EC 3.4.14.5) and angiotensinase A (EC 4.4.11.7) were purified to homogeneity from pooled urine concentrate of patients with renal damage, using ultrafiltration, ammonium sulphate precipitation, lectin affinity chromatography, FPLC-ion-exchange(Mono-Q-)chromatography, and FPLC-gel filtration (Superdex). Based on the specific enzyme activity of the starting material, dipeptidyl peptidase IV was enriched 1629 fold, angiotensinase A 1183 fold. The relative molecular masses, Michaelis constants and isoelectric points were determined. Negative staining of the purified enzymes revealed globular proteins (5-7 nm). Antisera raised against dipeptidyl peptidase IV and angiotensinase A reacted specifically with tubular and, in the case of anti-angiotensinase A sera, with tubular and glomerular structures. In addition, urinary membrane vesicles of proximal tubule origin were eluted with the void volume (Superdex-gel filtration), indicating heavy epithelial cell disintegration. Both soluble tissue enzymes (dipeptidyl peptidase IV, angiotensinase A) and vacuolar blebs shed from epithelia contribute to proteinuria, as was shown in patients with glomerulonephritis, interstitial nephritis, diabetic nephropathy and, for angiotensinase A, in patients with essential arterial hypertension.
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PMID:Biochemical and immunological properties of urinary angiotensinase A and dipeptidylaminopeptidase IV. Their use as markers in patients with renal cell injury. 136 94

Enzymuria is a frequent finding in patients suffering from various kidney diseases. The present study was undertaken to evaluate the clinical value of the determination of tubule-brush-border-associated dipeptidyl aminopeptidase IV (DAP IV) in the urine of patients with acute and chronic tubulointerstitial nephritis (n = 12), chronic glomerulonephritis (n = 15), essential arterial hypertension (n = 30), after kidney transplantation (n = 20), and of healthy control persons (n = 68). DAP IV was measured in spontaneously voided mid-stream morning urine ("second morning urine"), and was expressed as enzyme activity in units/liter. In order to account for variations due to urine concentration without collecting 24-hour specimens, a urinary DAP IV/creatinine ratio (DCR) was calculated. Furthermore, patterns of proteinuria were assayed by SDS-polyacrylamide gel electrophoresis. Urinary DAP IV activity of healthy controls was 4.94 +/- 0.12 U/l (DCR: 0.46 +/- 0.30 U/mmol creatinine) with only small day to day variations. Urinary DAP IV activity in patients with tubulointerstitial nephritis was significantly higher (15.5 +/- 15.6 U/l, p less than 0.05 vs controls; DCR: 1.67 +/- 0.97 U/mmol creatinine, p less than 0.001 vs controls). In patients with chronic glomerulonephritis urinary DAP IV activity was 9.6 +/- 5.6 U/l, p less than 0.05 (DCR: 1.22 +/- 0.75 U/mmol creatinine, p less than 0.05 vs controls). Increased urinary DAP IV activity in patients with chronic glomerulonephritis was associated with a mixed glomerulo-tubular pattern of proteinuria (as determined by SDS-PAGE).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urinary excretion of dipeptidyl aminopeptidase i.v. in patients with renal diseases. 232 11

Activity changes of the enzyme dipeptidyl peptidase IV (DP IV) were observed in connection with various diseases. The increase of serum activity in case of liver diseases and the decrease of activity in tissue and serum in case of malignant diseases are known. This investigation examined serum activity of DP IV at 168 patients with malignant diseases of the gastro-intestinal system. The 5%-, 50%- and 95%-percentiles of serum activity of DP IV were determined. Age and sex did not influence the activity of DP IV as less as attendant diseases like diabetes mellitus and hypertension. Malignant diseases of the gastro-intestinal system without liver metastases do have a significantly lower serum activity of DP IV. Malignant diseases of the pancreas and the bile duct and liver metastases lead to an increase of DP IV-serum activity.
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PMID:[Diagnostic value of the enzyme dipeptidyl peptidase IV (DP IV) in abdominal cancers]. 287 21

The course of the excretion of dipeptidyl-peptidase IV (DP IV)-alanine aminopeptidase, beta-glucuronidase and total protein with the urine was investigated during the treatment of 11 patients with pyelonephritis with gentamicin, after application of a renal radiographic contrast medium in 7 patients with arterial hypertension and after regional perfusion of an extremity in 10 patients with malignant melanoma. In the reference group in male test persons with 147.0 nmol/s X l a higher DP IV activity in the urine was recognized than in the female test persons (100.0 nmol/s X l). After application of the drugs a rhythmically intermitting increased excretion of all enzymes mentioned develops. The study confirms the usuability of the DP IV-activity for enzymological investigations of the urine.
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PMID:[Renal dipeptidylpeptidase IV excretion in drug-induced kidney changes]. 288 Apr 36

The proteases dipeptidyl peptidase IV, angiotensinase A and microsomal alanyl aminopeptidase are present in the human term placenta where they may be involved in the local modulation of placental blood pressure. In order to establish an in vitro model system to study the significance of these proteases in disorders related to pregnancy-induced hypertension, the activity of the proteases was localized histochemically in cultured explants of villi from human first trimester placentae. These studies revealed a similar distribution pattern of the activity of the proteases of cryostat sections of first trimester placental villi and in cultured tissue of the same placentae. Dipeptidyl peptidase IV and angiotensinase A activity were present in cytotrophoblast cells and dipeptidyl peptidase IV activity was found in the syncytiotrophoblast, respectively. Additionally, the activity of the proteases was visualized in various populations of stromal cells. Comparing our results with former studies, the protease activity pattern in first trimester placentae was found to be the same as in term placentae. Despite morphological changes of the tissue after 14 d in culture the localization of the proteases remained unchanged up to 52 d of culture. The results suggest that placental explants may serve as a suitable in vitro model for experimental studies on the role of proteases in pregnancy-induced hypertension.
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PMID:Enzyme histochemical evidence for the presence of potential blood pressure regulating proteases in cultured villous explants from human first trimester placentae. 790 30

Acute arterial hypertension provokes a rapid decrease in proximal tubule (PT) Na+ reabsorption, increasing flow to the macula densa, the signal for tubuloglomerular feedback. We tested the hypothesis, in rats, that Na+ transport is decreased due to rapid redistribution of apical Na+/H+ exchangers and basolateral Na+ pumps to internal membranes. Arterial pressure was increased 50 mmHg by constricting various arteries. We also tested whether transporter internalization occurred when PT Na+ reabsorption was inhibited with the carbonic anhydrase inhibitor benzolamide. Five minutes after initiating either natriuretic stimuli, cortex was removed, and membranes were fractionated by density gradient centrifugation. Urine output and endogenous lithium clearance increased threefold in response to either stimuli. Acute hypertension provoked a redistribution of apical Na+/H+ exchanger NHE3, alkaline phosphatase, and dipeptidyl peptidase IV to higher density membranes enriched in the intracellular membrane markers. Basolateral membrane Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity decreased 50%, 25-30% of the alpha 1-and beta 1-subunits redistributed to higher density membranes, and the remainder is attributed to decreased activity of the transporters. Benzolamide did not alter Na+ transporter activity or distribution, implying that decreasing apical Na+ uptake does not initiate redistribution or inhibition of basolateral Na(+)-K(+)-ATPase. We conclude that PT natriuresis provoked by acute arterial pressure is mediated by both endocytic removal of apical Na+/H+ exchangers and basolateral Na+ pumps as well as decreased total Na+ pump activity.
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PMID:Rapid redistribution and inhibition of renal sodium transporters during acute pressure natriuresis. 876 20

Capillaries are nonuniform thin tubes: The arteriolar and venular capillary portions express alkaline phosphatase (AP) and dipeptidyl peptidase IV (DPPIV), respectively. Differences in enzyme activities between arteriolar and venular capillary portions could be shown by staining sections of cardiac tissues for AP and DPPIV after coronary infusion of microspheres and by staining cultured endothelial cells that had been collected from coronary microvessels. Through use of a double staining method for AP and DPPIV, adaptive changes in the capillary network were studied in rat hearts exposed to cold, exercise, hypertension, chronic coronary occlusion, and transient coronary occlusion followed by reperfusion. Two patterns could be seen in the adaptations of the ventricular capillary network. The increase in the venular capillary portions is accompanied by remarkable increases in capillary density and capillary-to-myocyte ratio. The increase in the arteriolar capillary portion seemed to be accompanied by a decrease or only a limited increase in capillary density in stressed hearts. The increase in the total capillary density improves the capacity for oxygen transport to tissues with a high tissue perfusion and a short diffusion distance for oxygen. The increase in the arteriolar capillaries may also improve oxygen transport by increasing the arterial blood perfusing the tissue. This seems, however, a compensation for the limited angiogenesis: The alleviation of stresses, such as pharmacological treatment of the hypertrophied heart and reperfusion after transient ischemia, increases venular capillary portions and capillary density. These changes are discussed with immunohistochemical observations of rapid and prolonged expressions of angiogenic growth factors.
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PMID:Adaptive changes in the capillary network in the left ventricle of rat heart. 975 39

The mechanisms and myocardial alterations associated with NO-deficient hypertension are still far from clear. The aim of the present study was to focus on the enzyme histochemical and subcellular changes in the heart of L-NAME treated rats, as well as to examine the influence of captopril treatment. Wistar rats were administered either L-NAME (40 mg/kg/day) alone or together with captopril (100 mg/kg/day) for a period of 4 weeks. A significant increase of blood pressure confirmed the reliability of the model. The results showed that long-lasting L-NAME administration was accompanied by a decrease of endothelial NO-synthase activity and by a significant local decrease of the following enzyme activities: capillary-related alkaline phosphatase, 5'-nucleotidase and ATPase (but not dipeptidyl peptidase IV) and cardiomyocyte-related glycogen phosphorylase, succinic dehydrogenase, beta-hydroxybutyrate dehydrogenase and ATPases. No activity of these enzymes was found in the scar, whereas a marked increase of alkaline phosphatase and dipeptidyl peptidase IV activities was found in the foci of fibrotization. Histochemical changes correlated with subcellular changes, which were characterized by 1) apparent fibroblast activation associated with interstitial/perivascular fibrosis, 2) heterogeneous population of the normal, hypertrophic and injured cardiomyocytes, 3) enhancement of the atrial granules and their translocation into the sarcolemma, and 4) impairment of capillaries as well as by induction of angiogenesis. Similar alterations were also found in the heart of captopril co-treated rats, despite of the significant suppression of blood pressure. The results indicate that NO-deficient hypertension is accompanied by metabolic disturbances and ultrastructural alterations of the heart and these changes are probably not induced by the renin-angiotension system only.
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PMID:Chronic disturbances in NO production results in histochemical and subcellular alterations of the rat heart. 1080 8

Acute hypertension in Sprague-Dawley rats (SD) provokes a decrease in renal proximal tubule (PT) salt and fluid reabsorption, redistribution of apical Na/H exchanger isoform 3 (NHE3) and Na-P(i) cotransporter type 2 (NaPi2) out of the brush border into higher density membranes, and inhibition of renal cortical Na-K-ATPase (NKA) activity (41). The aims of this study were to determine 1) whether an increase in arterial pressure affects distribution or activity of Na transporters in the spontaneously hypertensive rat (SHR) and 2) whether development of chronic hypertension in SHR leads to persistent adaptive changes in NHE3 and NaPi2 distribution and/or NKA activity. Renal cortex Na transporter protein density distributions and activities were compared by subcellular fractionation in 1) adult SHR with an acute increase or decrease in arterial pressure and 2) young SD (YSD) and young SHR (YSHR) vs. adult SD and SHR. In adult hypertensive SHR NHE3 was shifted to membranes of higher densities, analogous to SD with acute hypertension, and there were no further changes with a further increase or decrease in arterial pressure. There was no change in total pool size of NHE3 in cortex in YSHR vs. SHR. NHE3, NaPi2, megalin, NKA alpha-/beta-subunit, dipeptidyl peptidase IV (DPPIV), and villin distributions were the same in YSHR vs. YSD. NHE3, NaPi2, and megalin shifted to higher densities in adult SHR, but not SD, with age. Basolateral NKA and apical alkaline phosphatase activities were 40% greater in YSHR than YSD and decreased to SD levels in adults. We conclude that there are persistent changes in Na(+) transporter distributions and activity in response to chronic hypertension in SHR that mimic the responses to acute hypertension seen in SD rats and that elevated sodium pump activity per transporter in YSHR may contribute to the generation of hypertension.
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PMID:Proximal tubule Na transporter responses are the same during acute and chronic hypertension. 1091 57

Bradykinin and substance P have been implicated as mediators in angiotensin-converting enzyme inhibitor (ACEI)-associated angioedema. Studies investigating the metabolism of bradykinin in sera from patients with a history of ACEI-associated angioedema and controls suggest that there is a defect in a non-ACE, non-kininase I pathway of bradykinin degradation, such as the aminopeptidase P (APP)/dipeptidyl peptidase IV (DPPIV) pathway. This study tested the hypothesis that serum APP or DPPIV activity is decreased in patients with ACEI-associated angioedema. APP and DPPIV activity were measured in sera collected from patients during ACEI-associated angioedema, from patients with a remote history of ACEI-associated angioedema, and from normotensive and untreated hypertensive controls. The effects of acute and chronic ACEI and corticosteroid treatment on serum DPPIV activity were also assessed. DPPIV activity was similar in normotensive volunteers (37.8 +/- 6.3 nmol/mL per min), in untreated hypertensive subjects who had been exposed previously to ACEI without angioedema (36.2 +/- 4.3 nmol/mL per min), in hypertensive patients with a remote history of angioedema (35.1 +/-8.5 nmol/mL per min), and in chronically ACEI-treated hypertensive subjects (36.1 +/- 5.6 nmol/mL per min). DPPIV activity decreased with increasing age (R(2)=0.10, P=0.016). Subject group significantly affected DPPIV activity (F=6.208, P=0.016) such that DPPIV activity was significantly lower in patients with ACEI-associated angioedema (26.9 +/- 4.1 nmol/mL per min) than in normotensive controls, in previously ACEI-exposed untreated hypertensive volunteers, or in ACEI-treated hypertensive volunteers, even after controlling for age. There was no effect of acute ACE inhibition or corticosteroids on DPPIV activity. With respect to APP activity, there was no difference between groups. These results suggest that DPPIV activity is depressed in individuals with hypertension during acute ACEI-associated angioedema.
Hypertension 2002 Feb
PMID:Dipeptidyl peptidase IV activity in patients with ACE-inhibitor-associated angioedema. 1188 90


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