What question did this study set out to answer?

To determine whether basal coronary vascular tone depends on endogenous endothelin release and assess the involvement of specific receptor subtypes and nitric oxide.

September 1, 1998The Journal of PhysiologyOpen Access

Role of endogenous endothelin in the regulation of basal coronary tone in the rat

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Why the study?

Does endothelin antagonism increase coronary flow in isolated rat hearts?

Population

Isolated, Krebs solution-perfused rat hearts

Comparison

Endothelin antagonists Ro61-0612, PD155080, and… vs Control or Krebs solution with L-NAME and/or…

Design

Preclinical, Hearts were randomly assigned to perfusion with plain Krebs…

Follow-up

30 minutes

Authors

AGAndrew GoodwinThe University of Sydney MAMohamed AmraniMohammed V University CGCaroline GrayUniversity of Sheffield

Discussion

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Implication

ETA antagonism augments coronary flow in isolated rat hearts; hypothesis-generating for human coronary tone modulation.

Key Points

To determine whether basal coronary vascular tone depends on endogenous endothelin release and assess the involvement of specific receptor subtypes and nitric oxide.
Measured coronary flow changes in isolated, Krebs solution-perfused rat hearts following 30-minute administration of endothelin antagonists Ro61-0612 (mixed ETA/ETB), PD155080 (ETA), or BQ788 (ETB).
Randomly assigned isolated hearts to perfusion with plain Krebs solution or solution containing L-NAME, indomethacin, or both, before measuring flow responses to Ro61-0612 and coronary sinus nitric oxide release.
Perfusion with mixed antagonist Ro61-0612 (10^-4 M) increased coronary flow by 57.8% versus control (P = 0.00001) and ETA antagonist PD155080 (10^-4 M) increased flow by 28.9% (P = 0.009), whereas ETB antagonist BQ788 caused no change.
Ro61-0612 increased coronary flow by 6.6 ± 0.8 ml min-1 in plain Krebs, 6.9 ± 0.5 ml min-1 with indomethacin, 3.8 ± 0.8 ml min-1 with combined L-NAME and indomethacin, and 3.3 ± 0.7 ml min-1 with L-NAME alone.
Coronary sinus nitric oxide release rose from 219.8 to 544.9 pmol min-1 g-1 after Ro61-0612 addition (P = 0.06), but remained undetectable in hearts treated with L-NAME.

Structured PICO

Does endothelin antagonism increase coronary flow in isolated rat hearts?

Population

Isolated, Krebs solution-perfused rat hearts

Intervention

Endothelin antagonists Ro61-0612 (mixed ETA/ETB), PD155080 (ETA), and BQ788 (ETB) administered over a 30 min period

Comparator

Control (plain Krebs solution) or Krebs solution with L-NAME and/or indomethacin

Outcome

Changes in coronary flowsurrogate

Endogenous endothelin plays a role in maintaining basal coronary tone mediated via ETA receptors, partially through modulation of endogenous NO release.

Cite This Study

Goodwin et al. (1998) studied this question.

synapsesocial.com/papers/6a830ab9992e36291ff46055 https://doi.org/10.1111/j.1469-7793.1998.549bh.x

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Role of endogenous endothelin in the regulation of basal coronary tone in the rat

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Role of endogenous endothelin in the regulation of basal coronary tone in the rat

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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