What question did this study set out to answer?

To determine whether endothelin-1 (ET-1) and endothelin-3 (ET-3) release endothelium-derived relaxing factor (EDRF) in isolated perfused rat and rabbit vascular beds.

January 1, 1989Journal of Cardiovascular Pharmacology

Endothelin-1 and Endothelin-3 Release EDRF from Isolated Perfused Arterial Vessels of the Rat and Rabbit

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Population

Isolated perfused arterial vessels of the rat (mesentery) and rabbit (aorta)

Comparison

Endothelin-1 and endothelin-3 vs Other agonists, Bay K 8644, or conditions with…

Design

Preclinical

Authors

TWTimothy D. WarnerNationwide Children's Hospital JMJane A. MitchellVascular / Pulmonary Vascular GNGilberto De NucciElectrophysiology

Discussion

Member takes

Implication

Hypothesis-generating for ET-mediated vasodilation; leaves open translation to human vascular disease or therapy.

Key Points

To determine whether endothelin-1 (ET-1) and endothelin-3 (ET-3) release endothelium-derived relaxing factor (EDRF) in isolated perfused rat and rabbit vascular beds.
Evaluated vascular responses to ET-1 (1–100 pmol) and ET-3 (1–300 pmol) in isolated perfused rat mesentery and luminally perfused rabbit aorta preparations.
Characterized EDRF involvement by testing responses following endothelial denudation and exposure to methylene blue (100 µM) or hemoglobin (30 µM).
Investigated calcium channel involvement through vascular challenges with potassium chloride (3 mM) and the dihydropyridine agonist Bay K 8644.
Both ET-1 and ET-3 induced EDRF release and vasodilation in rat mesentery, which was blocked by endothelial removal, methylene blue, or hemoglobin, while ET-1 displayed over 10-fold greater potency as a pressor agent than ET-3.
ET-3 acted as a more selective vasodilator than ET-1 because vasodilation induced by ET-1 was restricted and overwhelmed at higher doses by concurrent vasoconstriction.
ET-1-induced EDRF release in rabbit aorta was potentiated by potassium chloride infusion, whereas Bay K 8644 failed to stimulate EDRF release or elicit constriction in nondepolarized rat mesentery.

Structured PICO

Population

Isolated perfused arterial vessels of the rat (mesentery) and rabbit (aorta)

Intervention

Endothelin-1 (ET-1, 1-100 pmol) and endothelin-3 (ET-3, 1-300 pmol)

Comparator

Other agonists (acetylcholine, substance P, adenosine diphosphate), Bay K 8644, or conditions with endothelium removed/inhibitors (methylene blue, hemoglobin)

Outcome

Release of endothelium-derived relaxing factor (EDRF) and resulting vasodilatationsurrogate

ET-1 and ET-3 induce vasodilation through the release of EDRF in isolated rat and rabbit arterial vessels via non-dihydropyridine-sensitive calcium channels.

Cite This Study

Warner et al. (1989) studied this question.

synapsesocial.com/papers/6a7157bf660549caf2c5f87a https://doi.org/10.1097/00005344-198900135-00021

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Endothelin-1 and Endothelin-3 Release EDRF from Isolated Perfused Arterial Vessels of the Rat and Rabbit

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Endothelin-1 and Endothelin-3 Release EDRF from Isolated Perfused Arterial Vessels of the Rat and Rabbit

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

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