What question did this study set out to answer?

To determine whether renal vascular angiotensin receptors differ functionally from systemic vascular receptors and identify antagonists with increased specificity for the kidney.

March 1, 1977Journal of Clinical InvestigationOpen Access

Angiotensin antagonists with increased specificity for the renal vasculature.

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Population

42 dogs (26 normal dogs, 16 dogs with acute partial thoracic inferior vena caval occlusion)

Comparison

Angiotensin II, 1-des Asp AII, and angiotensin… vs Comparison between different angiotensin…

Design

Preclinical

Authors

KTK. TaubHarvard University WCWilliam J.H. CaldicottBoston Children's Hospital NHNorman K. HollenbergGeneral / Preventive / Lipids

Discussion

Member takes

Implication

May guide renal-selective vasodilator development; leaves open translation from animal data to clinical use.

Key Points

To determine whether renal vascular angiotensin receptors differ functionally from systemic vascular receptors and identify antagonists with increased specificity for the kidney.
Measured femoral and renal blood flow via electromagnetic flowmeter in 26 dogs given angiotensin II (AII), angiotensin III (AIII), and four competitive antagonists (P113; 8-Ala AII; 1-des Asp, 8-Ala AII; 1-des Asp, 8-Ile AII).
Tested vascular responses and cross-tachyphylaxis between AII and AIII across renal and systemic vascular beds.
Evaluated the hemodynamic effects of P113 versus 1-des Asp, 8-Ile AII in an additional 16 dogs with acute partial thoracic inferior vena caval occlusion to activate the renin-angiotensin system.
AII and AIII exhibited equivalent renal threshold doses (2.5±0.27 vs. 2.3±0.35 pmol/100 ml renal blood flow) and cross-tachyphylaxis, whereas AII exerted significantly greater pressor effects (P < 0.001) and femoral vasoconstriction (P < 0.001) than AIII.
In the kidney, P113 and 1-des Asp, 8-Ile AII provided equivalent blockade, with both showing superior antagonist potency compared to 8-Ala AII (P < 0.001) and 1-des Asp, 8-Ala AII (P < 0.001).
Under vena caval occlusion, 1-des Asp, 8-Ile AII produced larger, dose-dependent increases in renal blood flow with markedly less systemic hypotension compared to P113.

Structured PICO

Population

42 dogs (26 normal dogs, 16 dogs with acute partial thoracic inferior vena caval occlusion)

Intervention

Angiotensin II (AII), 1-des Asp AII (AIII), and angiotensin antagonists (1-Sar, 8-Ala AII [P113]; 8-Ala AII; 1-des Asp, 8-Ala AII; 1-des Asp, 8-Ile AII)

Comparator

Comparison between different angiotensin analogues and antagonists

Outcome

Femoral and renal blood flow and their responses to angiotensin II and AIIIsurrogate

Heptapeptide analogues of angiotensin II demonstrate greater specificity for the renal vasculature, suggesting utility in states of disordered renal perfusion.

Cite This Study

Taub et al. (1977) studied this question.

synapsesocial.com/papers/6a7e9c2cacd59602a78b9aff https://doi.org/10.1172/jci108668

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March 1, 1977Journal of Clinical InvestigationOpen Access

Angiotensin antagonists with increased specificity for the renal vasculature.

View Full Paper

Ask AI

Bookmark

Population

42 dogs (26 normal dogs, 16 dogs with acute partial thoracic inferior vena caval occlusion)

Comparison

Angiotensin II, 1-des Asp AII, and angiotensin… vs Comparison between different angiotensin…

Design

Preclinical

Authors

KTK. TaubHarvard University WCWilliam J.H. CaldicottBoston Children's Hospital NHNorman K. HollenbergGeneral / Preventive / Lipids

Discussion

Member takes

Implication

May guide renal-selective vasodilator development; leaves open translation from animal data to clinical use.

Key Points

To determine whether renal vascular angiotensin receptors differ functionally from systemic vascular receptors and identify antagonists with increased specificity for the kidney.
Measured femoral and renal blood flow via electromagnetic flowmeter in 26 dogs given angiotensin II (AII), angiotensin III (AIII), and four competitive antagonists (P113; 8-Ala AII; 1-des Asp, 8-Ala AII; 1-des Asp, 8-Ile AII).
Tested vascular responses and cross-tachyphylaxis between AII and AIII across renal and systemic vascular beds.
Evaluated the hemodynamic effects of P113 versus 1-des Asp, 8-Ile AII in an additional 16 dogs with acute partial thoracic inferior vena caval occlusion to activate the renin-angiotensin system.
AII and AIII exhibited equivalent renal threshold doses (2.5±0.27 vs. 2.3±0.35 pmol/100 ml renal blood flow) and cross-tachyphylaxis, whereas AII exerted significantly greater pressor effects (P < 0.001) and femoral vasoconstriction (P < 0.001) than AIII.
In the kidney, P113 and 1-des Asp, 8-Ile AII provided equivalent blockade, with both showing superior antagonist potency compared to 8-Ala AII (P < 0.001) and 1-des Asp, 8-Ala AII (P < 0.001).
Under vena caval occlusion, 1-des Asp, 8-Ile AII produced larger, dose-dependent increases in renal blood flow with markedly less systemic hypotension compared to P113.

Structured PICO

Population

42 dogs (26 normal dogs, 16 dogs with acute partial thoracic inferior vena caval occlusion)

Intervention

Angiotensin II (AII), 1-des Asp AII (AIII), and angiotensin antagonists (1-Sar, 8-Ala AII [P113]; 8-Ala AII; 1-des Asp, 8-Ala AII; 1-des Asp, 8-Ile AII)

Comparator

Comparison between different angiotensin analogues and antagonists

Outcome

Femoral and renal blood flow and their responses to angiotensin II and AIIIsurrogate

Heptapeptide analogues of angiotensin II demonstrate greater specificity for the renal vasculature, suggesting utility in states of disordered renal perfusion.

Cite This Study

Taub et al. (1977) studied this question.

synapsesocial.com/papers/6a7e9c2cacd59602a78b9aff https://doi.org/10.1172/jci108668

Also Consider

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