Intracerebroventricularly infused [ d-Arg 1]angiotensin III, is superior to [ d-Asp 1]angiotensin II, as a pressor agent in rats

John W Wright; Kim A Roberts; Vickie I Cook; Cathy E Murray; Michael F Sardinia; Joseph W Harding

doi:10.1016/0006-8993(90)90428-E

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Intracerebroventricularly infused [ d-Arg 1]angiotensin III, is superior to [ d-Asp 1]angiotensin II, as a pressor agent in rats

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Intracerebroventricularly infused [ d-Arg 1]angiotensin III, is superior to [ d-Asp 1]angiotensin II, as a pressor agent in rats

John W Wright, Kim A Roberts, Vickie I Cook, Cathy E Murray, Michael F Sardinia and Joseph W Harding

Brain research, Vol.514(1), pp.5-10

1990

DOI: https://doi.org/10.1016/0006-8993(90)90428-E

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https://hdl.handle.net/2376/114740

PMID: 2357530

Abstract

[ d-Arg 1]Angiotensin III

Angiotensin III

Amastatin

Rat

[ d-Asp 1]Angiotensin II

Blood pressure

Intracerebroventricular infusion

Angiotensin II

Bestatin

Sarthran

Two d-amino acid substitution angiotensin analogues were compared against native angiotensin II (AII) and angiotensin III (AIII) for their resistance to brain tissue-induced degradation and for pressor potency when intracerebroventricularly (i.c.v.) infused in Sprague-Dawley rats. The in vitro results indicate that [ d-Asp 1]AII was very resistant to degradation, AII and [ d-Arg 1]AIII were degraded at similar rates, while AIII was the most rapidly degraded. In vivo results revealed that AII, AIII and [ d-Arg 1]AIII produced greater pressor responses than [ d-Asp 1]AII. Intracerebroventricular pretreatment with the aminopeptidase A inhibitor, amastatin, siginificantly reduced the subsequent pressor response to i.c.v. infused [ d-Asp 1]AII presumably by inhibiting its conversion to AIII. In contrast, pretreatment with the aminopeptidase B inhibitor, bestatin, potentiated the subsequent pressor response to i.c.v. infused [ d-Arg 1]AIII, presumably by inhibiting the conversion of [ d-Arg 1]AIII to the less active hexapeptide AII(3–8). Next, i.c.v. pretreatment with the specific angiotensin receptor antagonist, [Sar 1, Thr 8]AII (Sarthran) was found to greatly diminish the subsequent pressor responses to i.c.v. infused [ d-Asp 1]AII and [ d-Arg 1]AIII, suggesting that these analogues are having their effect at the same brain angiotensin receptor site. These results support the hypothesis that AIII, or AIII-like ligands, may serve as the active form of brain angiotensin.

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Title: Intracerebroventricularly infused [ d-Arg 1]angiotensin III, is superior to [ d-Asp 1]angiotensin II, as a pressor agent in rats
Creators: John W Wright
Kim A Roberts
Vickie I Cook
Cathy E Murray
Michael F Sardinia
Joseph W Harding
Publication Details: Brain research, Vol.514(1), pp.5-10
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: Elsevier B.V
Identifiers: 99900548252401842
Language: English
Resource Type: Journal article

Intracerebroventricularly infused [ d-Arg 1]angiotensin III, is superior to [ d-Asp 1]angiotensin II, as a pressor agent in rats

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