What question did this study set out to answer?

To evaluate the structure-activity relationship and structural specificity of the C-terminal amino acid residue of angiotensin II analogues for adrenal medullary catecholamine secretion.

May 1, 1971Circulation Research

Adrenal Medullary Stimulation Induced by Angiotensin I, Angiotensin II, and Analogues

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Population

Isolated cat adrenal glands perfused retrograde at 1 ml/min with phosphate-buffered Locke's solution at 23…

Design

Preclinical

Authors

MPM J PeachLancaster University

Discussion

Member takes

Overview

Animal data on adrenal angiotensin receptors should not change practice; leaves open human validation and therapeutic relevance.

Key Points

To evaluate the structure-activity relationship and structural specificity of the C-terminal amino acid residue of angiotensin II analogues for adrenal medullary catecholamine secretion.
Perfused isolated cat adrenal glands retrograde at 1 ml/min with phosphate-buffered Locke's solution at 23–25°C with continuous catecholamine monitoring via automated trihydroxyindole assay.
Administered angiotensin II, angiotensin I, and multiple synthetic analogues (including [8-tyr], [8-ala], [8-APB], and [8-APIB] variants) by single injection (0.05–0.1 ml) or perfusion, alongside in vivo testing.
Assessed receptor specificity using 10-leu-C14-angiotensin I, angiotensin II antibodies, dimethylaminoethanol (DMAE) perfusions, nicotine, and bradykinin challenges.
Unlike systemic pressor activity, adrenal chromaffin tissue stimulation did not require an octapeptide length, an aromatic residue, or a free COOH group at position 8.
Cross-tachyphylaxis occurred between angiotensin II and all analogues except [8-APB]- and [8-APIB]-angiotensin II.
Angiotensin I directly stimulated medullary catecholamine release; both angiotensin I- and II-induced secretions were markedly potentiated by DMAE, consistent with action at a shared adrenal receptor.

Structured PICO

Population

Isolated cat adrenal glands perfused retrograde at 1 ml/min with phosphate-buffered Locke's solution at 23 to 25 C, and in vivo models

Intervention

Angiotensin I, Angiotensin II, and analogues ([8-(OMe)tyr]-angiotensin II; [8-tyr]-angiotensin II; [8-ala]-angiotensin II; [8-APB]-angiotensin II; [8-APIB]-angiotensin II; [1-asp(NH2),5-val]-angiotensin II; [1-asp,5-ileu]-angiotensin I; tetradecapeptide) administered by single injection (0.05 to 0.1 ml) or perfusion

Outcome

Adrenal medullary stimulation (catecholamine secretion)surrogate

Angiotensin I and II directly stimulate adrenal medullary catecholamine secretion via a common receptor, with structural requirements differing from those needed for maximum pressor activity.

Cite This Study

M J Peach (1971) studied this question.

synapsesocial.com/papers/6a7bcfd57d243c1b87ed13ef https://doi.org/10.1161/01.res.28.5.ii-107

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May 1, 1971Circulation Research

Adrenal Medullary Stimulation Induced by Angiotensin I, Angiotensin II, and Analogues

View Full Paper

Ask AI

Bookmark

Population

Isolated cat adrenal glands perfused retrograde at 1 ml/min with phosphate-buffered Locke's solution at 23…

Design

Preclinical

Authors

MPM J PeachLancaster University

Discussion

Member takes

Overview

Animal data on adrenal angiotensin receptors should not change practice; leaves open human validation and therapeutic relevance.

Key Points

To evaluate the structure-activity relationship and structural specificity of the C-terminal amino acid residue of angiotensin II analogues for adrenal medullary catecholamine secretion.
Perfused isolated cat adrenal glands retrograde at 1 ml/min with phosphate-buffered Locke's solution at 23–25°C with continuous catecholamine monitoring via automated trihydroxyindole assay.
Administered angiotensin II, angiotensin I, and multiple synthetic analogues (including [8-tyr], [8-ala], [8-APB], and [8-APIB] variants) by single injection (0.05–0.1 ml) or perfusion, alongside in vivo testing.
Assessed receptor specificity using 10-leu-C14-angiotensin I, angiotensin II antibodies, dimethylaminoethanol (DMAE) perfusions, nicotine, and bradykinin challenges.
Unlike systemic pressor activity, adrenal chromaffin tissue stimulation did not require an octapeptide length, an aromatic residue, or a free COOH group at position 8.
Cross-tachyphylaxis occurred between angiotensin II and all analogues except [8-APB]- and [8-APIB]-angiotensin II.
Angiotensin I directly stimulated medullary catecholamine release; both angiotensin I- and II-induced secretions were markedly potentiated by DMAE, consistent with action at a shared adrenal receptor.

Structured PICO

Population

Isolated cat adrenal glands perfused retrograde at 1 ml/min with phosphate-buffered Locke's solution at 23 to 25 C, and in vivo models

Intervention

Outcome

Adrenal medullary stimulation (catecholamine secretion)surrogate

Angiotensin I and II directly stimulate adrenal medullary catecholamine secretion via a common receptor, with structural requirements differing from those needed for maximum pressor activity.

Cite This Study

M J Peach (1971) studied this question.

synapsesocial.com/papers/6a7bcfd57d243c1b87ed13ef https://doi.org/10.1161/01.res.28.5.ii-107

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