December 1, 1989AJP Heart and Circulatory Physiology
Mechanism of contraction to endothelin in isolated porcine coronary artery
Population
Isolated porcine coronary artery
Comparison
Endothelin (ET) vs Other vasoconstrictors and K+ depolarization
Design
Preclinical
Authors
Discussion
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Implication
Hypothesis-generating for endothelin Ca-channel mechanisms in coronary tone; leaves open translation to human vessels.
Key Points
- To elucidate the cellular and pharmacological mechanisms underlying endothelin-induced contraction in isolated porcine coronary vascular smooth muscle.
- Assessed contractile tension in isolated porcine coronary artery rings exposed to endothelin alone and in combination with other vasoactive compounds and the calcium antagonist nicardipine.
- Evaluated smooth muscle cellular mechanisms by measuring 45Ca2+ influx and radioligand membrane receptor binding using [125I]iodipine.
- Endothelin triggered concentration-dependent vasoconstriction that was one to two orders of magnitude more potent than BAY K 8644, histamine, acetylcholine, or prostaglandin F2 alpha, reaching a maximum response equal to potassium depolarization.
- Contractions were competitively inhibited by nicardipine and occurred without triggering direct membrane depolarization.
- Endothelin accelerated 45Ca2+ uptake into smooth muscle cells at concentrations of 5 x 10^-10 M and 5 x 10^-8 M, which was blocked by nicardipine without altering specific [125I]iodipine binding.
Structured PICO
P
Population
Isolated porcine coronary artery
I
Intervention
Endothelin (ET)
C
Comparator
Other vasoconstrictors (BAY K 8644, histamine, acetylcholine, prostaglandin F2 alpha) and K+ depolarization
O
Outcome
Contractile response and mechanism of vasoconstriction (Ca2+ influx)surrogate
Endothelin induces potent vasoconstriction in porcine coronary arteries by accelerating calcium influx through voltage-dependent calcium channels at a binding site distinct from dihydropyridines.
Cite This Study
Kasuya et al. (1989) studied this question.