Refractoriness to the effect of endothelin-1 in porcine ciliary arteries

PURPOSE: Endothelin-1 (ET) is an important molecule in vascular physiology. After an acute stimulation with ET, vessels are to some extent temporarily refractory to further stimulation. However, few details are known about this phenomenon. The aim of our study was to verify the existence of refractoriness in ophthalmic ciliary arteries and, if present, to analyze its time course. METHODS: Twenty freshly isolated porcine ciliary arteries were placed in a myograph system to measure isometric forces. Each vessel was stimulated with 10(-7) M ET twice. The experiment was performed in 5 groups of vessels, which differed in the time interval between the initial and the second stimulation with ET. The intervals were 15 min, 30 min, 1 h, 2 h, and 4 h, respectively. RESULTS: The vasoconstrictive response to re-exposure to ET was time-dependently reduced. The response was lowest after 15 min (22% of baseline response), and then the sensitivity slowly recovered and was finally normal again after 4 h. CONCLUSIONS: Our experiment with isolated porcine ophthalmic ciliary arteries revealed a refractoriness phase to ET after an acute stimulation with ET. This refractoriness was transient and disappeared after 4 h. The lowest response was observed in the group of vessels re-exposed 15 min after the first stimulation.