Characterization of Immunoreactive Angiotensin in Canine Cerebrospinal Fluid as Des-Asp1-Angiotensin II

Hutchinson, J. S.; Csicsmann, J.; Korner, Paul I.; Johnston, Colin I.

doi:10.1042/cs0540147

Cited by 11 publications

(12 citation statements)

References 16 publications

(13 reference statements)

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“…80 However when angiotensin III was added to dog CSF and incubated at 37°C, the levels as measured by radioimmunoassay were altered little over 4 hours and in some instances up to 24 hours. These findings are in agreement with those of Hutchinson et al, 19 who also observed minimal angiotensinase activity in the CSF of dogs. Third, it is conceivable that sodium pentobarbital anesthesia slowed or otherwise altered CSF production or circulation so that angiotensin levels within the cerebral ventricles were not accurately reflected by cisternal sampling.…”

Section: Discussionsupporting

confidence: 83%

“…It is pertinent to note that the radioimmunoassay used in these studies utilized an antibody raised against angiotensin II but which cross-reacted 100% with the heptapeptide angiotensin III; therefore, the observations in CSF are valid whichever of the two peptides is the important end product of this renin-angiotensin system. 19 It appears from the above data that immunoreactive angiotensin II levels in CSF and plasma have separate regulatory systems. However, there are a number of other possible explanations or interpretations.…”

Section: Discussionmentioning

confidence: 99%

“…The current study therefore set out to determine whether there was any parallelism in the control of the peripheral and the central nervous renin-angiotensin systems. Further, since immunoreactive angiotensin II in dog cerebrospinal fluid (CSF) may in fact consist largely of the heptapeptide des-Asp^angiotensin II, 19 the possibility that this peptide within CSF might simply reflect concurrent plasma levels was explored. …”

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confidence: 99%

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Independence of the central nervous and the peripheral renin-angiotensin systems in the dog.

Nicholls¹

1979

Hypertension

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SUMMARY What regulates the activity of the central nervous renln-angiotensln system is not known. To define whether control of this central system is linked to that in the periphery, simultaneous blood and cerebrospinal fluid (CSF) samples for measurement of immunoreactive angiotensin II were drawn from anesthetized dogs during hemorrhage, furosemide-induced Tolume depletion, insulln-hypoglycemia, betaadrenergic blockade and saline infusion. Despite rigorous increments or decrements in plasma immunoreactive angiotensin II, CSF levels remained stable. Since immunoreactive angiotensin II in dog CSF is claimed to be mainly the heptapeptide des-Asp'-angiotensln II (angiotensin III), the possibility that the level of this peptide within CSF simply reflects plasma concentrations was assessed by infusing angiotensin III (2.5 and 25 ng/kg/min intravenously, each for 60 minutes) and monitoring plasma and CSF peptide levels. Whereas plasma immunoreactive angiotensin II levels increased appropriately across the infusions, no change in CSF levels was observed. These studies indicate that angiotensiii III does not cross the blood-CSF barrier, at least in the short term. 18 There is evidence that the reninangiotensin system within the central nervous system might be involved in the pathogenesis of some forms of hypertension in animals 1117 and in man. 18While the physiological and pathophysiological importance of this system is being vigorously researched, the question of what regulates its activity has received less attention. The current study therefore set out to determine whether there was any parallelism in the control of the peripheral and the central nervous renin-angiotensin systems. Further, since immunoreactive angiotensin II in dog cerebrospinal fluid (CSF) may in fact consist largely of the heptapeptide des-Asp^angiotensin II, 19 the possibility that this peptide within CSF might simply reflect concurrent plasma levels was explored. 228 Materials and MethodsAll experiments were carried out in male mongrel dogs weighing 19.1-35 kg. Each dog was used on only one occasion. Fluid and dietary intake were not restricted before the experimental day. Anesthesia was induced with sodium pentobarbital (30 mg/kg I.V.) and maintained with additional amounts of the barbiturate as required (7.5 mg/kg every 2 hours in most cases). Two cannulae were inserted into peripheral leg veins, one for infusion, the other for blood withdrawal. With the dog's head held in flexion, a 17-gauge needle (Portex Epidural Minipacks) was introduced into the cisternal space under strictly sterile conditions. Clear CSF, uncontaminated by blood, could be aspirated rapidly, and in many cases streamed under pressure from the cisternal needle. In the few instances that blood-contaminated CSF was obtained, the dog was excluded from the study. A 45-minute stabilization period prior to blood and CSF sampling was observed after insertion of the cisternal needle. As a routine, two "basal" CSF and blood samples were obtained for analysis before the experimenta...

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Independence of the central nervous and the peripheral renin-angiotensin systems in the dog.

Nicholls¹

1979

Hypertension

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“…It is interesting in this respect that angiotensin 111, an intermediate of this metabolic pathway as outlined above, exerts pronounced biological activity in the brain [S]. The functioning of this pathway in vivo is supported by the fact that part of the angiotensin I1 immunoreactivity in canine cerebrospinal fluid [38] and in rat brain tissue [39] has been identified as angiotensin 111. Removal of C-terminal phenylalanine from angiotensin 11, as occurred at the acidic pH, is the most efficient route to rapid inactivation of the peptide, as this removal is accompanied by a dramatic fall in receptor binding and a loss of biological activity.…”

Section: Discussionmentioning

confidence: 96%

Proteolytic Conversion of Angiotensins in Rat Brain Tissue

Tonnaer¹,

Engels²,

Wiegant³

et al. 1983

Eur J Biochem

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The proteolytic conversion of angiotensins in rat brain preparations was studied. Angiotensin 1 was converted into angiotensin I1 by enzymes which were associated with a synaptic membrane preparation, while angiotensin I1 was relatively resistant to proteolysis by these enzymes. Angiotensin I1 was rapidly metabolized at both pH 7.4 and pH 5.4 by enzymes in the soluble fraction of a synaptosomal preparation. One of the fragments formed at pH 7.4 was characterized as angiotensin 111. At pH 5.4 only one fragment was generated which was characterized as angiotensin-(1-7)-heptapeptide. Enzymatically generated angiotensin 11 and 111 displayed pronounced biological activity in the brain, whereas angiotensin-(l-7)-heptapeptide was inactive. These data indicate a route for the generation, and the inactivation of biologically active angiotensins in the brain.Angiotensin I1 (see Fig. 1) is an octapeptide which elicits apparent biological activity when injected into the brain or into the cerebral ventricular system (see [I] for review). Angiotensin I1 and the components necessary for the enzymatic generation of the octapeptide as well as for the expression of its biological activity have been found in brain tissue (see [2, 31 for reviews). Thus in addition to angiotensin 11, brain tissue contains angiotensinogen, renin-like enzymes, angiotensin I, angiotensin-I-converting enzyme, angiotensin 11 receptors and angiotensinases. The activity of the brain renin-angiotensin system in vivo may be inferred from the effects ofpharmacological blockade of this peptidergic system at the level of renin-like enzymes [4 -61, angiotensin-I-converting enzyme [4] or angiotensin I1 receptors [4, 71. Despite many studies on the activity in vivo of the reninangiotensin system in the brain, little is known about the subcellular localization of the various constituents of this system and their co-operation as a functional unit. The very short latencies to the biological effects upon intracerebroventricular injection of angiotensin TI and angiotensin I1 fragments [4,8] suggest a localization of the angiotensin I1 receptors in the plasma membrane of central nervous cells. Indeed, high affinity binding of angiotcnsin I1 to purified synaptosomes has been demonstrated [9]. Thus, angiotensin I1 might exert its effects in the central nervous system by modulation of neurones at the synaptic level.

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“…Several studies have revealed the presence of angiotensinogen, isorenin, angiotensin I (ANG I), ANG I converting enzyme and ANG II in the brain or in the cerebrospinal fluid in a number of mammalian species (Ganten et al, 1971;Yang and Neff, 1972;Slavin, 1975;Reid, 1977;Ganten and Speck, 1978;Inagami et al, 1978). The presence of angiotensin III (ANG III) in the cerebrospinal fluid has also been described (Hutchinson et al, 1978). It is well known that injection of ANG II directly into the brain ventricles produces an increase in arterial blood pressure (Smookler et al, 1966;Severs, 1976).…”

Section: Synopsismentioning

confidence: 99%