Endothelin-1 and endothelin-3 regulate differently vasoconstrictor responses of smooth muscle of the porcine coronary artery.
1. Using front-surface fluorometry of fura-2 and medial strips of the porcine coronary artery, we investigated mechanisms by which endothelin-1 (ET-1) and ET-3 function as vasoconstrictors. 2. In the presence of extracellular Ca2+(1.25 mM), ET-1 (10(-10)-10(-7) M) increased cytosolic Ca2+ concentrations ([Ca2+]i) and tension, in a concentration-dependent manner. ET-1, at concentrations greater than 10(-8) M, induced an abrupt elevation of [Ca2+]i which reached a transient peak (the first component, [Ca2+]i-rising phase) and subsequently declined ([Ca2+]i-declining phase) to reach a lower sustained phase (the second component, steady-state phase), while the tension rose monotonically to reach a peak and then slightly and gradually declined. ET-1, at concentrations lower than 10(-8) M, induced slowly developing and sustained increases in [Ca2+]i and tension ([Ca2+]i-rising phase followed by steady-state phase). All concentrations of ET-1 increased tension more slowly than [Ca2+]i. 3. In the presence of extracellular Ca2+, ET-3 (10(-8)-10(-5) M) induced concentration-dependent increases in [Ca2+]i and tension. However, the maximal elevations of [Ca2+]i and tension induced by ET-3 were substantially smaller than those induced by ET-1, indicating the involvement of an ETA receptor subtype. ET-3, at concentrations greater than 6 x 10(-7) M, caused biphasic slowly developing increases in [Ca2+]i and tension. At concentrations lower than 10(-6) M, ET-3 caused monophasic increases in [Ca2+]i and tension. At all concentrations of ET-3, the time courses of increases in [Ca2+]i and tension were similar.(ABSTRACT TRUNCATED AT 250 WORDS)[1]References
- Endothelin-1 and endothelin-3 regulate differently vasoconstrictor responses of smooth muscle of the porcine coronary artery. Ushio-Fukai, M., Nishimura, J., Kobayashi, S., Kanaide, H. Br. J. Pharmacol. (1995) [Pubmed]
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