What question did this study set out to answer?

To determine whether phosphoramidon inhibits the in vivo enzymatic conversion of big endothelin-1 to active endothelin-1 and prevents vasoconstriction in the human forearm vascular bed.

September 1, 1995British Journal of PharmacologyOpen Access

Phosphoramidon inhibition of the in vivo conversion of big endothelin‐1 to endothelin‐1 in the human forearm

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Why the study?

Does phosphoramidon inhibit the in vivo conversion of big endothelin-1 to endothelin-1 and prevent its associated vasoconstriction in the human forearm?

Population

Human subjects undergoing in vivo forearm studies

Comparison

Brachial artery co-infusion of phosphoramidon… vs Infusion of big endothelin-1 or endothelin-1…

Design

Other

Follow-up

60 minutes

Authors

CPChristopher PlumptonGlaxoSmithKline (United Kingdom)WHWilliam G. HaynesOregon National Primate Research Center DWDavid J. WebbVascular Medicine

Discussion

Member takes

Implication

Hypothesis-generating for ECE inhibition in human vascular tone; requires clinical trials before therapeutic consideration.

Key Points

To determine whether phosphoramidon inhibits the in vivo enzymatic conversion of big endothelin-1 to active endothelin-1 and prevents vasoconstriction in the human forearm vascular bed.
Infused endothelin-1 (5 pmol min⁻¹) or big endothelin-1 (50 pmol min⁻¹) into the brachial artery of human forearms for 60 minutes, alone and with phosphoramidon (30 nmol min⁻¹).
Quantified forearm blood flow and measured venous plasma levels of immunoreactive endothelin-1, big endothelin-1, and C-terminal fragment using selective solid-phase extraction and radioimmunoassays.
Infusion of big endothelin-1 alone significantly elevated venous levels of endothelin (from 2.2 to 7.7 pM, P < 0.05), big endothelin-1 (from 0 to 386.0 pM, P < 0.05), and C-terminal fragment (from 0.2 to 37.0 pM, P < 0.05), while reducing forearm blood flow from 3.0 to 1.6 ml dl⁻¹ min⁻¹ (P < 0.05).
Co-infusion of phosphoramidon with big endothelin-1 completely abolished the increase in immunoreactive endothelin-1 and the reduction in blood flow, although C-terminal fragment was still detected.
Infusion of endothelin-1 alone increased plasma endothelin levels from 2.3 to 55.2 pM (P < 0.05) and reduced blood flow from 2.6 to 1.7 ml dl⁻¹ min⁻¹, neither of which was altered by phosphoramidon co-infusion.

Structured PICO

Does phosphoramidon inhibit the in vivo conversion of big endothelin-1 to endothelin-1 and prevent its associated vasoconstriction in the human forearm?

Population

Human subjects undergoing in vivo forearm studies

Intervention

Brachial artery co-infusion of phosphoramidon and big endothelin-1 (50 pmol min-1) or endothelin-1 (5 pmol min-1)

Comparator

Infusion of big endothelin-1 or endothelin-1 alone, and basal levels

Outcome

Venous plasma levels of immunoreactive endothelin-1 (ET-1), big ET-1, C-terminal fragment (CTF), and forearm blood flowsurrogate

Phosphoramidon inhibits the conversion of big ET-1 to ET-1 in the human forearm, demonstrating that a phosphoramidon-sensitive endothelin converting enzyme mediates big ET-1-induced vasoconstriction.

Cite This Study

Plumpton et al. (1995) studied this question.

synapsesocial.com/papers/6a8309abc4b5dbf8331f2843 https://doi.org/10.1111/j.1476-5381.1995.tb16669.x

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Phosphoramidon inhibition of the in vivo conversion of big endothelin‐1 to endothelin‐1 in the human forearm

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Phosphoramidon inhibition of the in vivo conversion of big endothelin‐1 to endothelin‐1 in the human forearm

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider