Studies on angiotensinogen of plasma and cerebrospinal fluid in normal and hypertensive human subjects.

Ito, Toru; Eggena, Peter; Barrett, J.; Katz, Daniel H.; Metter, Jeffrey; Sambhi, Mohinder P.

doi:10.1161/01.hyp.2.4.432

Cited by 42 publications

(9 citation statements)

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“…As discussed by Hilgenfeldt ( 1984), Murakami et al (1984), and Ito et al (1980), the production of different biochemical forms of Aogen is probably indicative of different physiological roles for the renin-angiotensin system in various tissues. Certainly the presence of overwhelming levels of y-Aogen in CSF reflects a difference in the utilization and metabolism of the prohormone in the microenvironment of brain tissue as compared to circulating plasma.…”

Section: Discussionmentioning

confidence: 96%

“…Neither brain nor plasma Aogen has been completely characterized. Whereas many investigators Ito et al, 1980;Murakami et al, 1984) have identified a single molecular weight form of Aogen by gel filtration, sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE) analyses of rat plasma have resolved two molecular weight forms (Bouhnik et al, 1981;Hackenthal, 1982: Voigt et al, 1982). Three molecular weight forms of Aogen have been recently identified in dog plasma by SDS-PAGE and anion-exchange HPLC: these have been designated a-, @-.…”

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confidence: 99%

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Angiotensinogen in Cerebrospinal Fluid Corresponds Chromatographically to the γ‐Form of Plasma Angiotensinogen

Moffett

1987

Journal of Neurochemistry

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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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Section: Discussionmentioning

confidence: 96%

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confidence: 99%

Angiotensinogen in Cerebrospinal Fluid Corresponds Chromatographically to the γ‐Form of Plasma Angiotensinogen

Moffett

1987

Journal of Neurochemistry

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“…Therefore, hypertension is not necessarily related to an increment in CSF angiotensinogen concentration. 4 Water deprivation induced a significant increase in PRA and no significant changes in plasma or CSF angiotensinogen concentration. Chen et al 18 have reported increased plasma renin substrate concentration and significant elevation of the prohormone in some brain regions in rats deprived of water during 72 hours.…”

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confidence: 92%

“…In this regard, significant elevations in net angiotensinogen content have been found in selected areas of the rat brain 32 hours after bilateral nephrectomy.' 4 Adrenalectomy and nephrectomy induced parallel changes in plasma and CSF angiotensinogen concentration while DOC-salt treatment resulted in a clear dissociation of the prohormone in both compartments. This effect differs from that produced by glucocorticoids which is one of the most effective stimuli for increased angiotensinogen secretion by the liver 13 l6 and at the same time produces a significant increment in the central concentration of renin substrate.…”

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confidence: 97%

Angiotensinogen concentration in the cerebrospinal fluid in different experimental conditions in the rat.

Ruíz¹,

Basso²,

Grinspon³

et al. 1983

Hypertension

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SUMMARY 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. Plasma angiotensinogen concentration was significantly elevated by Nx and significantly diminished by Adx, DOC-salt, and DOC-salt plus captopril, and captopril treatment. T HE presence of angiotensinogen in the brain and cerebrospinal fluid (CFS) of rabbits, dogs, rats, and humans has been clearly demonstrated. '^ Biochemical analysis has shown a similar molecular weight and electrophoretic mobility for plasma and CSF renin substrate; moreover, the final product released by both prohormones was identical to synthetic angiotensin I (AI) with respect to isoelectric point or pressor response.3 Clear differences between CSF and plasma angiotensinogen were also observed. In this regard, central renin substrate was heterogeneous with respect to isoionic points; the plasma protein presented only one component. In addition, im- munological differences between the central and peripheral renin substrate were also established.5 Although not definitively demonstrated, most of the available information supports a central origin for the angiotensinogen present in the brain and CSF of mammals and humans. Some experimental conditions determine a similar change in peripheral and central prohormone. 6 However, in a previous report 7 we found a clear dissociation between plasma and brain angiotensinogen in DOC-salt-treated hypertensi...

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“…Schelling and Felix 14 have recently examined angiotensinogen levels in seven brain areas from 9-week-old stroke-prone SHR and reported that differences exist in the levels of angiotensinogen relative to Wistar-Kyoto rats (WKY). Ho et al 26 have observed that angiotensinogen levels are elevated in the CSF of hypertensive humans. To establish more clearly whether a link exists between the activity of the brain angiotensin system and hypertension, we have measured angiotensinogen in 38 discrete brain areas from the hypertensive SHR and the normotensive WKY.…”

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confidence: 99%

Angiotensinogen levels in the brain and cerebrospinal fluid of the genetically hypertensive rat.

Healy¹,

Printz²

1985

Hypertension

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SUMMARYThe present experiments were designed to document changes in the regional distribution of angiotensinogen in the rat brain with the development of hypertension in spontaneously hypertensive rats (SHR) relative to age-matched normotensive Wistar-Kyoto rats (WKY). Levels of angiotensinogen were measured in discrete brain nuclei and cerebrospinal fluid from rats at 4, 7, and 16 weeks of age and in cerebrospinal fluid obtained by cisternal puncture at 7 and 16 weeks. Agedependent changes in angiotensinogen were found, with levels higher in both strains at 4 weeks of age compared with 7 or 16 weeks. In contrast, plasma levels of angiotensinogen were essentially the inverse of the brain levels, low at 4 weeks and higher at 7 and 16 weeks. Levels in a number of regions adjacent to the rostral third ventricle from the 4-week-old SHR (prehypertensive phase) were significantly elevated relative to the WKY (p < 0.05), while levels in the amygdala and posterior hypothalamus were significantly lower in the SHR (p < 0.05). In 7-week-old rats (evolving phase), levels in nine brain regions were significantly elevated in the SHR relative to the WKY and included the nucleus tractus solitarii (p < 0.01). Unlike the prehypertensive and evolving phases, in 16-week-old rats (maintenance phase) only two brain areas, the nucleus of the diagonal band and the lateral hypothalamus, had significantly elevated levels in the SHR (p < 0.05). Cerebrospinal fluid levels of angiotensinogen did not correlate well with brain levels of angiotensinogen. Compared with those in WKY, cerebrospinal fluid levels were lower in the 7-week-old SHR while brain levels were generally higher. Conversely, in 16-week-old rats angiotensinogen levels were slightly elevated in cerebrospinal fluid from the SHR relative to the WKY. These results indicate that local concentrations of brain angiotensinogen may be more relevant to the etiological process or development of hypertension in the SHR than are cerebrospinal fluid levels and that local regulation of this prohormone exhibits a developmental dependency. (Hypertension 7: 752-759, 1985) KEY WORDS * brain angiotensinogen • spontaneously hypertensive rat • development anteroventral third ventricle * cerebrospinal fluid E VIDENCE for the existence of a brain angiotensin system includes the demonstration that most components of a putative angiotensin II (ANG II) biosynthetic pathway have been identified in the central nervous system (CNS), and that ANG II administered centrally elicits a characteristic response pattern consisting of elevated blood pressure, increased drinking, elevated vasopressin secretion, and increases in sodium appetite.1 " 3 These physiological responses have led investigators to examine the contributions of a putative brain angiotensin system to the development or maintenance of hypertension in the

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Studies on angiotensinogen of plasma and cerebrospinal fluid in normal and hypertensive human subjects.

Cited by 42 publications

References 15 publications

Angiotensinogen in Cerebrospinal Fluid Corresponds Chromatographically to the γ‐Form of Plasma Angiotensinogen

Angiotensinogen in Cerebrospinal Fluid Corresponds Chromatographically to the γ‐Form of Plasma Angiotensinogen

Angiotensinogen concentration in the cerebrospinal fluid in different experimental conditions in the rat.

Angiotensinogen levels in the brain and cerebrospinal fluid of the genetically hypertensive rat.

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