July 1, 1990Journal of Cardiovascular Pharmacology
Effects of Endothelin-1 in Isolated Perfused Rat Heart
Population
Isolated isovolumic rat hearts perfused with Krebs-Henseleit buffer at constant pressure
Design
Preclinical
Follow-up
90 min
Authors
Discussion
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Implication
Endothelin-1 pathways may modulate coronary tone with prostaglandin and ACE inhibitor interactions; hypothesis-generating in rat hearts and should not yet change practice.
Key Points
- To examine the coronary vascular actions of endothelin-1 and determine its physiological interactions with other hormonal and receptor systems in isolated perfused rat hearts.
- Perfused isolated isovolumic rat hearts with Krebs-Henseleit buffer under constant pressure across single (4–400 pmol) and cumulative (0.04–400 pmol) doses of endothelin-1.
- Assessed coronary flow responses in the presence of phentolamine, propranolol, nifedipine, indomethacin, captopril, and nitroglycerin.
- High doses of endothelin-1 (40 and 400 pmol) caused a biphasic coronary response featuring transient early vasodilation followed by persistent, irreversible vasoconstriction that virtually abolished coronary flow at 400 pmol.
- Endothelin-1-mediated vasoconstriction was unaltered by alpha-adrenergic, beta-adrenergic, or calcium-channel blockade and resisted nitroglycerin reversal, but was significantly augmented by indomethacin and slightly attenuated by captopril.
Structured PICO
P
Population
Isolated isovolumic rat hearts perfused with Krebs-Henseleit buffer at constant pressure
I
Intervention
Endothelin-1 (single bolus 4-400 pmol or cumulative doses 0.04-400 pmol) alone or with phentolamine, propranolol, nifedipine, indomethacin, captopril, or nitroglycerin
O
Outcome
Coronary flow and vasoconstrictionsurrogate
Endothelin-1 induces potent, irreversible coronary vasoconstriction in the isolated rat heart, which is exacerbated by prostaglandin inhibition and slightly attenuated by ACE inhibition.
Cite This Study
Neubauer et al. (1990) studied this question.