Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:022433 (Angiotensinogen)
 335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensinogen is the precursor of biologically active peptide angiotensin II and its hepatic synthesis is increased by the induction of acute inflammation. Studies were carried out to know whether the rise in plasma angiotensinogen is actually involved in the activity of the renin-angiotensin system during acute inflammation. The plasma level of angiotensinogen in rats was increased to 2.5 times the normal level 16 h after the induction of acute inflammation by administration of lipopolysaccharide (LPS). The plasma renin concentration (PRC) was decreased to about 40% of the normal level concomitantly with a reduction of plasma renin activity (PRA) at 4 h after LPS administration. In contrast, 16 h after LPS injection, when plasma angiotensinogen showed a high level and PRC had recovered to the normal range, PRA was increased to 1.7 times the normal level. These results indicate that acute inflammation induced by LPS causes a biphasic change in the generation of angiotensin I, i.e., an early decrease depending upon the reduction of PRC and later increase depending upon elevation of the angiotensinogen concentration.
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PMID:Changes in activity of the renin-angiotensin system of the rat by induction of acute inflammation. 264 7

Angiotensin II (AII) is present in gonadotropes in rats, and there are AII receptors on lactotropes and corticotropes. AII may be a paracrine mediator that stimulates the secretion of prolactin and adrenocorticotropin (ACTH) at the level of the pituitary, but additional research is needed to define its exact role. Angiotensinogen may also reach the gonadotropes via a paracrine route. On the other hand, there is considerable evidence that brain AII stimulates the secretion of luteinizing hormone (LH) by increasing the secretion of LH-releasing hormone, and that this effect is due to AII-mediated release of norepinephrine from noradrenergic nerve terminals in the preoptic region of the hypothalamus. In addition, brain AII inhibits the secretion of prolactin, probably by increasing the release of dopamine into the portal hypophyseal vessels. Circulating AII stimulates the secretion of a third anterior pituitary hormone, ACTH, by acting on one or more of the circumventricular organs to increase the secretion of corticotropin-releasing hormone.
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PMID:Angiotensin II in the brain and pituitary: contrasting roles in the regulation of adenohypophyseal secretion. 265 66

In vivo generation of angiotensins depends upon both plasma renin and angiotensinogen concentrations. Those factors which may influence hepatic angiotensinogen synthesis and release were examined. We have evaluated in vivo the effects of converting enzyme inhibition on several plasma renin-angiotensin system components, and, using an in vitro preparation of liver slices, we also investigated the effects of converting enzyme inhibition on the synthesis and release of hepatic angiotensinogen. Angiotensinogen concentrations were determined by two different methods. The first was an indirect enzymatic assay which measures the amount of angiotensin I liberated from plasma by an excess of renin. The second was a direct RIA that measures both angiotensinogen and its inactive residue the des-angiotensin I-angiotensinogen. The difference between the methods represents the circulating levels of des-angiotensin I-angiotensinogen. Captopril administration in sodium-depleted rats increased plasma concentrations of renin, des-angiotensin I-angiotensinogen, and angiotensin I and decreased plasma angiotensinogen concentration measured by both methods. Plasma des-angiotensin I-angiotensinogen was significantly correlated to plasma renin concentration, which suggests an increase in the consumption of angiotensinogen when the renin secretion is extremely increased. The angiotensinogen liver content and in vitro angiotensinogen release were decreased in sodium-depleted rats treated with a converting enzyme inhibitor, and these parameters were negatively correlated to in vivo plasma levels of renin, angiotensin I, and des-angiotensin I-angiotensinogen. They were positively correlated to plasma angiotensinogen concentration measured by the indirect assay. These data suggest that captopril administration during sodium depletion has two simultaneous effects: it increases angiotensinogen consumption and second, decreases angiotensinogen production and release.
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PMID:Liver angiotensinogen synthesis and release during captopril treatment in sodium-depleted rats. 303 Jun 98

A comparative immunocytochemical and electron microscopic study was performed on renal biopsies from two children with classical Bartter's syndrome (BS) and three children with a recently described variant, the so-called hyperprostaglandin E-syndrome (HES). Compared to age-matched controls, kidney specimens from patients with BS and HES disclosed a marked hypertrophy and hyperplasia of the juxtaglomerular apparatus (JGA). In addition, in HES focal tubular and interstitial calcifications accompanied by interstitial fibrosis and tubular atrophy were noted. On immunocytochemistry, chronic stimulation of the JGA in BS and HES was characterized by an increase in the number of renin-positive cells, particularly in the media of afferent arterioles, but also in efferent arterioles and in the glomerular stalk. The length of the renin-positive portion of the preglomerular arterioles was significantly increased when compared to controls (100 +/- 32 vs. 49 +/- 17 microns; p less than 0.001). In addition, the immunoreactivity of individual renin-positive cells was markedly enhanced. On electron microscopy, "hypertrophy" of the RER and of Golgi complexes with paracrystalline deposits in dilated RER cisterns and protogranules indicated an increased renin synthesis. Renin could be identified in mature secretory granules as well as protogranules by immune electron microscopy. Angiotensinogen was present in hypertrophied epithelial cells of Bowman's capsule. Converting-enzyme reactivity was observed in controls as well as in BS and HES in the brush border of the proximal tubule. In contrast to previous reports, Angiotensin II was completely negative in control as well as in diseased kidneys. We conclude from our results that both BS and HES are characterized by a marked activation of the JGA and severe stimulation of the renin-angiotensin system. Since activation of this system, however, leads--independently of the primary stimulus--to qualitatively very similar morphological reactions, these results do not implicate a common pathogenetic mechanism to both conditions.
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PMID:The juxtaglomerular apparatus in Bartter's syndrome and related tubulopathies. An immunocytochemical and electron microscopic study. 312 15

The antihypertensive effects of 2 different peptidic substrate analogs: AG 84-10 AG 85-12 were investigated in renovascular hypertensive (Goldblatt, 2 kidneys--1 clip) Sprague-Dawley male rats. AG 84-10 (Ac-Pro-Phe-His-Leu-Val-Tyr) is similar to Angiotensinogen 6-13 and AG 85-12 (Ac-Ile-His-Pro-Phe-His-Leu) mimics the C-terminal portion of Angiotensin I. 6 weeks after clipping, hemodynamic profiles of these molecules [Heart rate (HR), mean arterial pressure (MAP), filling parameters, peripheral vascular resistances (PR) and cardiac output (CO)] during 90 minutes, were determined in the anesthetized animals. CO was measured using a thermodilution technique. Parallel radio-immunologic dosages of plasma renin activity were performed. Measurements and calculation of previously defined hemodynamic variables, every 10 minutes, demonstrated that: AG 84-10 exerted an early but transient decrease of MAP and PR, an increase of CO without modification of other hemodynamic parameters. AG 85-12 induced a late and durable decrease of MAP and PR with a significant decrease of heart rate, but without modification of CO and other hemodynamic variables. Example: PR mmHg/ml/mn/kg (mean +/- SD): *p less than 0.05 ** p less than 0.01. (Table: see text). The different levels of plasma renin activity were in accordance with hemodynamic data. So, the 2 peptidic substrate analogs elicited antihypertensive effects with a more efficient action of AG 85-12.
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PMID:[Cardiovascular effects of peptide inhibitors of the renin-substrate reaction in rats with renovascular hypertension. Goldblatt: 2 kidneys--1 clip]. 314 5

It has been proposed that feedback by angiotensin II, the effector peptide of the renin-angiotensin system stimulates hepatic angiotensinogen synthesis, since long-term infusion of this octapeptide in vivo induced an increase in plasma angiotensinogen concentrations. In the present study, the effects of angiotensin II (9 and 90 nmol/l) on angiotensinogen messenger (m)RNA concentrations and on angiotensinogen secretion of freshly isolated rat hepatocytes were compared with those of glucocorticoids (hydrocortisone, 10(-4) mol/l, and dexamethasone, 10(-5) mol/l). Angiotensin II and the glucocorticoids elevated angiotensinogen mRNA concentrations two- to threefold. Angiotensinogen secretion rates were correspondingly increased with a time lag of about 2 h. Differences in the time-course of changes in mRNA following onset or decay of the hormonal effect suggest that angiotensin II and glucocorticoids express their effects by different intracellular mechanisms. This view is supported by the observation that angiotensin II but not dexamethasone has a stabilizing effect on angiotensinogen mRNA, when further synthesis was blocked by actinomycin D.
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PMID:Angiotensin II controls angiotensinogen secretion at a pretranslational level. 324 Dec 34

Angiotensinogen (Aogen) (CA 11002-13-14), the prohormone of the neuro- and vasoactive peptide angiotensin II (Ang II) (CA 11128-99-7), is found in dog brain as well as in dog plasma. At 2-4 micrograms/ml CSF, Aogen comprises 1-2% of the total protein in dog CSF. Immunopurified CSF and plasma Aogen were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and anion-exchange HPLC. Two major (alpha- and beta-) forms and one minor (gamma-) form of Aogen were observed in dog plasma. The majority of Aogen in dog CSF was chromatographically identical to the gamma-form of plasma Aogen; alpha- and beta-Aogen forms comprised less than 5% of the total CSF Aogen. The N-terminal amino acid sequences of alpha-, beta-, and gamma-Aogen identified these proteins as members of the Aogen family. The N-terminal amino acid sequence of CSF gamma-Aogen was Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-Leu-Leu-Val-Tyr-Ser-Lys-Ser-Ser-(X)-Glu- . More basic than either alpha- or beta-Aogen, gamma-Aogen was shown to be a glycoprotein with an apparent molecular weight (Mr) of 58,000. CSF [des Ang I]-Aogen exhibited a greater anion-exchange HPLC retention. CSF, however, contained only minor amounts of [des Ang I]-Aogen. These analyses have demonstrated that brain overwhelmingly releases one particular Aogen into the CSF; however, very little of this brain Aogen is utilized for the production of Ang I.
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PMID:Angiotensinogen in cerebrospinal fluid corresponds chromatographically to the gamma-form of plasma angiotensinogen. 330 5

The mechanism by which anti-renin antibody inhibits renin activity was studied by following the kinetics of the reaction with angiotensinogen or a low molecular weight synthetic substrate, tetradecapeptide (TDP). Two monoclonal antibodies (70 pM) inhibited the production of angiotensin I from angiotensinogen but they differed when hog TDP was used as a substrate. R3-47-10 partially and non-competitively inhibited, whereas R3-36-16 stimulated the activity of renin. This is in contrast to the effects of the synthetic renin inhibitor, CGP 29 287, which competitively inhibits the enzyme activity with both substrates. These antibodies probably bind to the renin molecule on the flap which protects the active cleft. Angiotensinogen may be prevented from entering the cleft due to steric hindrance from bound antibody. However TDP, because of its smaller size may still be able to reach the catalytic site. In addition R3-36-16 might freeze the flap in an open position allowing a greater turnover of TDP whereas R3-47-10 may prevent the flap from fully opening and thereby hinder the reaction of TDP with the active site.
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PMID:Modification of the interaction of human renin with different substrates by monoclonal antibodies. 330 93

The effects of bilateral nephrectomy or a sham operation on plasma angiotensinogen and on the different kininogens were studied in the rat. Total plasma kininogen was measured by RIA of kinins after trypsin hydrolysis. In addition, the high molecular weight (HMW) kininogen and the low molecular weight (T)-kininogen were specifically quantified by using direct RIAs. Angiotensinogen was measured by RIA of angiotensin I after exhaustion by renin. Three groups of control, nonoperated, bilaterally nephrectomized and sham-operated rats were studied in each experiment. Twenty-four hours after either a bilateral nephrectomy or a sham operation total plasma kininogen was elevated approximately 5 times when compared to control rats. Time course measurements from 0 to 48 h in 3 other groups of control, bilaterally nephrectomized and sham-operated rats demonstrated that kininogen gradually increased at 12, 24, and 48 h after the surgery and that the elevation observed in plasma kininogen appeared to be entirely due to an increase in T-kininogen levels. There was no difference in T-kininogen levels between bilaterally nephrectomized and sham-operated animals. By contrast HMW kininogen was neither influenced by surgery nor by nephrectomy. Angiotensinogen increased more than 8 times in bilaterally nephrectomized rats but displayed only little changes in sham-operated animals. During the course of this experiment it was observed that also in control animals submitted to repeated skin incision and venipuncture for blood sampling at the jugular vein, T-kininogen increased dramatically in plasma, but reached values lower than in sham-operated or bilaterally nephrectomized rats. In a third experiment performed in normal rats it was found that T-kininogen levels were more than 3 times elevated over initial values 24 h after a single blood sampling at the jugular vein. These results indicate that T-kininogen but not HMW kininogen is very sensitive to surgery, perhaps as a result of increased T-kininogen synthesis due to an inflammatory reaction. The T-kininogen might participate in the inflammatory reaction that occurs at the site of tissue injury and in the healing process. As there was no difference in T-kininogen, and in HMW kininogen levels between bilaterally nephrectomized and sham-operated rats, the kidneys do not seem to play an important role in the regulation of plasma kininogens. Angiotensinogen, HMW kininogen, and T-kininogen are therefore regulated separately after nephrectomy or surgery.
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PMID:Differential effects of nephrectomy and surgery on plasma kininogens and angiotensinogen in the rat. 337 Dec 63

The distribution of angiotensinogen-like immunoreactivity in the rat brain was investigated using specific antisera against pure rat plasma angiotensinogen in conjunction with the sensitive streptavidin-biotin peroxidase method. Angiotensinogen antisera were shown by radioimmunoassay and Western blotting to recognize angiotensinogen from both rat plasma and cerebrospinal fluid, and to cross-react with des-AI-angiotensinogen (100%) but not with angiotensin I and II, tetradecapeptide, luteinizing hormone-releasing hormone, rat albumin and angiotensinogen from eight other species. Angiotensinogen-like immunoreactivity was detected throughout the rat brain in both neuroglia and neurons. The highest concentration of neuroglial angiotensinogen-like immunoreactivity was in the hypothalamus and preoptic areas, with moderate to heavy concentrations in the mesencephalon and myelencephalon. The cerebellum demonstrated neuroglial staining in the granular layer and fibre tracts. Very little neuroglial staining was noted in the cerebral cortex or olfactory bulbs. Neuronal immunostaining was observed throughout the globus pallidus and the caudate putamen, in various parts of the thalamus and the supraoptic nucleus of the hypothalamus. In the midbrain moderate immunostaining was observed in periaquaductal central gray, the deep mesencephalic nucleus, the inferior colliculus and in scattered cells in the anterior mesencephalon. In the medulla, neuronal staining was localized to the vestibular nuclei and to other cell bodies mainly in the dorsolateral regions. In the cerebellum, staining was noted mainly in the deeper cerebellar nuclei and in the Purkinje cells. Immunostaining in the cerebral cortex was localized to the cingulate cortex and the primary olfactory cortex. Light staining was present in the endopiriform cortex and in scattered neurons adjacent to the external capsule. In the olfactory bulbs light neuronal staining was mainly associated with the mitral cell layer. The widespread distribution of angiotensinogen-like immunoreactivity supports the view that it is synthesized in the central nervous system and forms part of a brain renin-angiotensin system. In addition, its presence at sites other than those normally associated with the control of blood pressure and fluid and electrolyte homeostasis suggests that its involvement may not be limited to these regulatory functions.
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PMID:Immunocytochemical localization of angiotensinogen in the rat brain. 339 83


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