Different mobilization of calcium in endothelin-1-induced contractions in human arteries and veins: effects of calcium antagonists.
We studied the role of extra- and intracellular Ca2+ in endothelin-1-induced contractions of the isolated human internal mammary artery and vein. Veins were more sensitive to the peptide than arteries (concentration shift:3.2-fold; n = 4-10, p less than 0.05). The Ca2+ antagonists darodipine, verapamil, and diltiazem (10(-7)-10(-6) M) did not prevent the response to endothelin-1 in both vessels. In contrast, darodipine (10(-8)-10(-6) M), added after the contraction had developed, partially reversed the response in the artery (26 +/- 7%) and particularly in the vein (67 +/- 5%; n = 4, p less than 0.005 compared to the artery). Removal of extracellular Ca2+ reduced the contractions to endothelin-1 (10(-8) M) in the artery (control: 89 +/- 4% of 100 mM KCl; Ca2(+)-free: 68 +/- 4% n = 4-6, p less than 0.01), but not in the vein except at low concentrations (10(-9) M) of the peptide. After removal of intracellular Ca2+ with caffeine in the artery, endothelin-1 still evoked a contraction (17 +/- 3%, n = 3; p less than 0.005 vs. control), while in the vein the response was abolished. Thus, mobilization of Ca2+ during endothelin-1-induced contractions differs in the human internal mammary artery and vein. In the artery, the contraction depends on extracellular Ca2+, intracellular caffeine-sensitive Ca2+ stores, and a caffeine-insensitive component, while in veins, mobilization of intracellular Ca2+ is most important. Ca2+ antagonists do not prevent, but partially reverse, endothelin-1-induced contractions indicating that voltage-operated Ca2+ channels do not initiate but contribute to the maintenance of the response.
Yang
Z
Z
Department of Research, University Hospital, Basel, Switzerland.
Bauer
E
E
von Segesser
L
L
Stulz
P
P
Turina
M
M
Lüscher
T F
TF
D002110:Caffeine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D008323:Mammary Arteries; D009119:Muscle Contraction / Q000187:drug effects*; D014680:Veins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D016232:Endothelins; D002110:Caffeine