What question did this study set out to answer?

To assess the individual contributions and functional crosstalk of endothelin ETA and ETB receptors during vasoconstriction in isolated rat small mesenteric arteries.

March 1, 1997British Journal of PharmacologyOpen Access

Activation of endothelin ETA receptors masks the constrictor role of endothelin ETB receptors in rat isolated small mesenteric arteries

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Population

Rat isolated, endothelium-denuded, 3rd generation small mesenteric arteries

Comparison

Endothelin-1 with or without ETA receptor… vs ET-1 alone or different combinations of…

Design

Preclinical

Authors

EMEmma J. MickleySt Bartholomew's Hospital GGGillian A. GrayHeart Failure / Cardiomyopathy DWDavid J. WebbBrigham and Women's Hospital

Discussion

Member takes

Implication

May require dual ETA/ETB antagonism to fully inhibit ET-1 constriction in mesenteric arteries; leaves open human relevance.

Key Points

To assess the individual contributions and functional crosstalk of endothelin ETA and ETB receptors during vasoconstriction in isolated rat small mesenteric arteries.
Mounted third-generation isolated rat mesenteric arteries denuded of endothelium under pressure.
Assessed concentration-dependent vascular contractions induced by endothelin-1 (ET-1) and the selective ETB agonist sarafotoxin S6c (SRTX S6c).
Characterized receptor subtype interactions using selective antagonists BQ-123 (ETA) and BQ-788 (ETB), SRTX S6c-mediated ETB desensitization, and the dual ETA/ETB antagonist TAK-044.
ET-1 produced concentration-dependent contractions with a pD2 of 9.86, whereas SRTX S6c contracted only 53% of arteries and elicited a markedly lower maximum response (Emax 10.7 ± 2.9% vs. 101.9 ± 2.6% of KCl-induced contraction).
Neither ETB receptor desensitization with 10⁻⁷ M SRTX S6c nor ETB blockade with BQ-788 significantly shifted the ET-1 concentration-response curve on their own.
BQ-123 alone inhibited ET-1 responses only at concentrations above 10⁻¹⁰ M, but combining BQ-123 with BQ-788, combining BQ-123 with ETB desensitization, or administering dual antagonist TAK-044 significantly inhibited all ET-1 concentrations and shifted the response curve rightward.

Structured PICO

Population

Rat isolated, endothelium-denuded, 3rd generation small mesenteric arteries

Intervention

Endothelin-1 (ET-1) with or without ETA receptor antagonist (BQ-123), ETB receptor agonist (SRTX S6c), ETB receptor antagonist (BQ-788), or ETA/ETB antagonist (TAK-044)

Comparator

ET-1 alone or different combinations of antagonists/agonists

Outcome

Concentration-dependent contractionssurrogate

Dual ETA/ETB receptor antagonism may be required to completely inhibit constrictor responses to ET-1 in small mesenteric arteries due to receptor crosstalk.

Cite This Study

Mickley et al. (1997) studied this question.

synapsesocial.com/papers/6a830b2bc0477142e551aa2b https://doi.org/10.1038/sj.bjp.0701036

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Activation of endothelin ETA receptors masks the constrictor role of endothelin ETB receptors in rat isolated small mesenteric arteries

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Activation of endothelin ETA receptors masks the constrictor role of endothelin ETB receptors in rat isolated small mesenteric arteries

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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