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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensinogen was measured in the brain and cerebrospinal fluid (CSF) of spontaneously hypertensive rat (SHR) and the normotensive Wistar-Kyoto strain at 4, 7 and 16 weeks of age. Levels of angiotensinogen were elevated in a number of areas of SHR, primarily in the 4 and 7 week old animals. CSF levels did not correlate with the brain levels. These results suggest that the regulation of the brain angiotensin system maybe altered during the development of hypertension.
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PMID:Changes in brain angiotensinogen during development of hypertension. 635 56

Angiotensinogen is the most important component of the renin-angiotensin system present in the cerebrospinal fluid (CSF) of the rat. Its physiological significance as well as its origin have not been clearly elucidated. In this experiment we have examined plasma renin activity (PRA) and plasma and CSF angiotensinogen concentration under the following experimental conditions in male rats of the Wistar strain: 1) adrenalectomy (Adx) 4 days prior to sample collection; controls were sham Adx animals; 2) nephrectomy (Nx) 48 hours before blood and CSF collection; controls were sham Nx rats; 3) DOC-salt treatment (Cortexon depot, 50 mg/kg.s.c. twice a week) plus saline to drink was given during 4 weeks; controls were intact rats; 4) DOC-salt plus captopril: captopril (100 mg/kg/day) in the drinking fluid was added to the treatment of experimental and control animals of Group 3; 5) two-kidney, two clip hypertension: silver clips placed in both renal arteries 8 weeks before samples collection; control: sham-operated rats; 6) water deprivation: rats deprived of water for 5 days; controls: intact rats; 7) peripheral sympathectomy: 6-hydroxydopamine (6-HODA) injected s.c. from birth until 16 weeks of age, adrenodemedullectomy and adrenal denervation performed at 8 weeks; controls were vehicle-injected animals. Determination of angiotensinogen concentration in plasma and CSF was accomplished by incubation of the samples with excess hog renin. The angiotensin I released as well as PRA were evaluated using an specific radioimmunoassay technique. PRA was significantly increased by Adx, captopril treatment, and water deprivation, and was almost suppressed by Nx, DOC-salt, and DOC-salt plus captopril treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Angiotensinogen concentration in the cerebrospinal fluid in different experimental conditions in the rat. 636 Aug 80

Evidence for an intracellular pathway for angiotensin synthesis in the central nervous system (CNS) was examined using immunohistochemistry to compare the distribution of angiotensin I (AI), AII, angiotensinogen, and renin in the hypothalamic paraventricular nuclei (PVN) and supraoptic nuclei (SON), median eminence (ME), and pituitary gland in intact and nephrectomized rats. In intact rats injected intracerebroventricularly (i.c.v.) with colchicine, AII neurons were found in the parvocellular PVN, and terminals were seen in the external lamina of the ME. In the pituitary gland, AII was localized within cells of the anterior and intermediate lobes, whereas the posterior pituitary was unstained. In contrast, 24 to 48 hours following nephrectomy, AII-labeled neurons were observed in the magnocellular PVN and SON, even without the aid of i.c.v. colchicine. Likewise, axons within the internal layer of the ME were now labeled, but the pituitary was completely devoid of staining except for the intermediate lobe. AI-labeled neurons were observed only in the parvocellular PVN. Angiotensinogen was localized in the mediobasal hypothalamus, but the PVN and SON were not labeled. Immunoreactive renin was localized within the magnocellular PVN, SON, and posterior lobe of the pituitary in nephrectomized and intact animals. Because of the close overlap of AI and AII staining, these results suggest that AI and AII could represent a precursor product relationship in the CNS. In contrast, in the intact animals, renin and angiotensinogen do not appear to be associated with AII. However, a possible relationship between AII and renin may exist in the magnocellular PVN and SON, since labeled neurons were seen in these nuclei following nephrectomy.
Hypertension
PMID:Distribution of immunoreactive angiotensin II, angiotensin I, angiotensinogen and renin in the central nervous system of intact and nephrectomized rats. 637 93

The Ren-1 locus of mice encodes the protease renin, which with converting enzyme processes angiotensinogen to the potent vasopressor angiotensin II. Some strains of mice appear to carry a duplication of the renin structural gene (Ren-2) near the Ren-1 locus. Strains with the gene duplication can exhibit as much as 100-fold higher levels of submaxillary gland renin compared to strains with a single gene copy. In contrast, kidney renin levels appear to be unaffected by the gene duplication. Sequence analysis of a 319 bp renin cDNA recombinant isolated from a kidney library from the two-gene strain DBA/2Ha corresponds to a transcript of the Ren-1 gene. Moreover, a single base substitution of A for G at residue #996 in the kidney renin mRNA creates a potential glycosylation recognition site that may, in part, account for the differential glycosylation of kidney and submaxillary gland renins. In addition, our tissue surveys indicate that mature mRNAs from the Ren loci are detectable in adrenal gland and testes, as well as sublingual and parotid salivary glands, and reveal length variation for the renin transcripts in at least the submaxillary gland.
Hypertension
PMID:Tissue and gene specificity of mouse renin expression. 637 91

Three stable monoclonal antibodies to rat angiotensinogen were obtained by fusing myeloma cells with spleen cells from Balb/c mice injected with pure rat angiotensinogen. They were screened by their binding to pure iodinated angiotensinogen and to insolubilized angiotensinogen in a solid phase assay. The titers of the three antibodies varied from 1/3500 to 1/35000, their dissociation constants from 2.5 X 10(-8) M to 3.8 X 10(-10) M, and the sensitivity of the assay ranged from 200 to 10 pmol of pure angiotensinogen. These monoclonal antibodies did not recognize either angiotensin peptides or angiotensinogen from other species, except for mouse angiotensinogen, which cross-reacted with the different antibodies from 0 to 25%. Rat cerebrospinal fluid angiotensinogen, plasma des-angiotensin I-angiotensinogen, and plasma angiotensinogen were equally recognized by these monoclonal antibodies. Contrary to what was observed for a polyclonal antiserum, the monoclonal antibodies failed to inhibit the renin-angiotensinogen reaction in vitro.
Hypertension
PMID:Production and characterization of monoclonal antibodies to rat angiotensinogen. 639 87

Angiotensin II and angiotensin III, the active peptides of the renin-angiotensin system, are produced by a cascade of enzymatic reactions, whose initial step is the reaction between renin and its substrate, angiotensinogen. In plasma, the concentration of angiotensinogen is a limiting factor: the Km of the enzymatic reaction is between 1 and 2 microM depending on the species. It is therefore of interest to measure its level in plasma and tissues and to examine the main factors which may influence its synthesis and release. The complete purification of angiotensinogen has made possible the preparation of specific antibodies which cross-react with both angiotensinogen and its residue, des-angio I-angiotensinogen, and are currently used in radioimmunoassays and immunohistochemical studies. A small amount of angiotensinogen is stored in hepatic cells, where it can be detected by immunofluorescence and measured by radioimmunoassay. It is also present in proximal tubular cells of the kidney, probably reabsorbed from glomerular filtrate, but it is absent from juxtaglomerular cells. Several hormones are able to increase liver synthesis of angiotensinogen and its release. Thyroxine, angiotensin II, dexamethasone, ethinyl-estradiol and binephrectomy increase both synthesis and release. Adrenalectomy and converting-enzyme inhibition are accompanied by an increased peripheral consumption of plasma angiotensinogen, and by accumulation of des-angio I-angiotensinogen whose metabolism and role are unknown. The major role of angiotensinogen in renal hemodynamics is demonstrated by its effects on the isolated perfused kidney, an experimental observation which parallels the clinical observation of women on estroprogestative therapy, whose renal blood flow is reduced, even in the absence of a detectable increase in their blood pressure. A better knowledge of renin substrate structure in various species is a necessary requirement for the design of inhibitory analogs of angiotensinogen which will have application for the treatment of hypertension and oedema.
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PMID:Biochemistry and regulation of angiotensinogen. 664 Sep 61

Angiotensinogen and the product of its hydrolysis by renin, des-angiotensin I-angiotensinogen, were quantitated in human plasma and in cerebrospinal fluid (CSF) by a direct RIA. This assay was developed using polyclonal antibodies raised against pure human angiotensinogen. The antibodies recognized only primate angiotensinogen and des-angiotensin I-angiotensinogen. Results obtained with the direct RIA were compared with those of the indirect assay which measures angiotensinogen through angiotensin I liberated by an excess of renin. Both assays gave almost identical results in normal subjects whereas in three different conditions characterized by a high renin level (severe hypertension plus low sodium diet, converting enzyme inhibition, and adrenal insufficiency) higher results were obtained by the direct assay. This difference between the results of both methods was attributed to des-angiotensin I-angiotensinogen accumulation which is detected only in the direct assay. CSF angiotensinogen had similar immunochemical properties to plasma angiotensinogen and could also be measured by the direct RIA. Isoelectric focusing of plasma angiotensinogen and des-angiotensin I-angiotensinogen revealed a similar microheterogeneity. Microheterogeneity was also a characteristic of CSF angiotensinogen, but its isoelectric point was more basic than plasma angiotensinogen.
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PMID:Characterization of plasma and cerebrospinal fluid human angiotensinogen and des-angiotensin I-angiotensinogen by direct radioimmunoassay. 674 61

From the in vitro and in vivo measurements of the components of the renin-angiotensin system (RAS) in the cerebrospinal fluid (CSF) of rats and dogs, it was concluded that angiotension II (ANG II) is not generated within the CSF in significant amounts, since renin was found to be unmeasurable in CSF under most circumstances. The specific concentrations of angiotensinogen and of converting enzyme (CE) were high. Angiotensin I (ANG I) concentrations were low in CSF, while ANG II levels were comparable to those measured in plasma under control conditions. Neither ANG I nor ANG II penetrated from the blood into the brain ventricles of rats, provided that no unrealistically high doses of ANG II were administered intravenously. This holds true even if high blood pressure increases were induced by intravenous ANG II infusion in deoxycorticosterone acetate (DOCA) and salt-treated rats. However, increased ANG II concentrations were measured in CSF perfusate, when the blood-brain barrier (BBB) was opened by the intracarotid injection of a hyperosmolar urea solution. The brain ventricular perfusion of increasing concentrations of ANG II revealed constant recovery of less than 40%. CSF did not contain angiotensinase activity, but ANG II degradation was high in some periventricular regions. ANG II, the ANG II antagonist saralasin, and the CE inhibitor captopril, respectively, escaped from CSF into circulation when high doses of these substances were applied intraventricularly. We conclude that ANG II in the CSF does not originate from and is not related to plasma ANG II. It is probably not generated within the CSF. ANG II may be synthetized in the brain tissue and be released into the brain ventricles where its rapid degradation occurs in contact with circumventricular structures.
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PMID:Components of the renin-angiotensin system in the cerebrospinal fluid of rats and dogs with special consideration of the origin and the fate of angiotensin II. 700 24

Chemical modification of the backbone at the cleavage site in the (6-13)-octapeptide of equine angiotensinogen resulted in greatly increased binding affinity and resistance to cleavage by renin. The D-His6-Tyr13 octapeptide analog containing the reduced bond -CH2-NH-instead of a peptide bond -CO-NH- at the Leu10-Leu11 linkage (H-77) was a powerful in vitro inhibitor of canine renin (IC50 = 24nM). It gave an IC50 of 1 microM against human renin and 0.6 microM against rat renin. In sodium-depleted conscious dogs, infusion of H-77 caused dose-related falls of plasma angiotensin I plasma angiotensin II concentration and mean arterial pressure; the minimum effective dose was 0.1 mg . kg-1 hr-1. Similar infusions of H-77 in chronically catheterized rats have no effect on blood pressure or plasma angiotensin II concentration. Thus, the in vitro effect of H-77 as an inhibitor of renin in dog, human, and rat plasma was paralleled by its action in the whole animal.
Hypertension
PMID:H-77: a potent new renin inhibitor. In vitro and in vivo studies. 704 Feb 40

Inactive renin was partially purified from 4.5 liters of human plasma (502-fold, specific activity 0.8 X 10(-3) Goldblatt units/mg protein) and from 207 g renal cortex (103-fold, 52 X 10(-3) Goldblatt units/mg). In contrast to active renin, inactive renin from each source bound to Cibacron blue-agarose and was unable to bind to pepstatin-Sepharose. Both plasma and renal inactive renin had weaker affinity for anion-exchange resins than the active form, both bound to concanavalin A-Sepharose and were eluted with carbohydrate, and both bound tightly to hydrophobic gels. Each substance could be isolated in a completely inactive form during small-scale pilot studies, but "spontaneous" activation did occur, to a limited degree, during large-scale purification; this was possibly due to a plasma serine protease that fractionated with inactive renin during the initial purification steps. Both plasma and renal inactive renin were activated irreversibly by trypsin. Following activation, each substance lost it ability to bind to Cibacron blue-agarose. Each could be activated fully by acidification at 4 degrees C, but this activation was reversed during subsequent incubation at higher temperature and pH. There was no evidence of acid protease activity in either preparation. Activated inactive renin from both plasma and kidney were identical to partially-purified active renal renin in terms of pH optimum (pH 5.5-6.0) and reaction kinetics (Km 0.8-1.3 microM) with homologous angiotensinogen, noncompetitive inhibition by pepstatin (ki 2.5-3.5 microM), and an identical inhibition profile by monospecific antirenin antibodies. These results suggest that inactive renin from plasma and kidney may be the same substance and that their activated forms are similar to the endogenously produced active enzyme, consistent with the possibility that inactive renin is a precursor of circulating active renin.
Hypertension
PMID:Biochemical similarity of partially purified inactive renins from human plasma and kidney. 704 Feb 42


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