TY - JOUR
T1 - Direct vasodilative effect of FK506 on porcine mesenteric artery in small bowel transplantation
AU - Akiyoshi, Junko
AU - Ieiri, Satoshi
AU - Nakatsuji, Takanori
AU - Taguchi, Tomoaki
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/12
Y1 - 2009/12
N2 - Background: Tacrolimus (FK506) is widely used as an immunosuppressive drug in small bowel transplantation. However, its precise effects on the vascular tone of the transplanted organ have not been studied. This study aimed to clarify the effects of FK506 on the porcine mesenteric artery. Methods: The effects of FK506 on the changes in cytosolic Ca2+ concentration ([Ca2+]i) and force using fura-2 fluorometry were investigated in mesenteric arterial strips of the porcine small intestine. The effects of FK506 on the activity of voltage-dependent Ca2+ channels and receptor-operated Ca2+ channels using high K+ (118 mmol/L K+) depolarization and thromboxane A2 analog (U46619) stimulation were also examined. Results: FK506 inhibited the force development induced by 118 mmol/L K+ depolarization and 1 μmol/L U46619 stimulation in a concentration-dependent manner. The extent of inhibition of this contraction was greater than that of the K+-induced contraction, and its inhibitory potency was about 10-fold. FK506 (10 μmol/L) inhibited the increases in [Ca2+]i (24.9% ± 7.4%) and the force development (52.0% ± 5.6%) induced by 1 μmol/L U46619, respectively. Conclusions: FK506 induces arterial relaxation by decreasing [Ca2+]i. Pretreatment of a graft with FK506 may reduce the risk of vasospasm, ischemia-reperfusion injury, and thrombosis in small bowel transplantation.
AB - Background: Tacrolimus (FK506) is widely used as an immunosuppressive drug in small bowel transplantation. However, its precise effects on the vascular tone of the transplanted organ have not been studied. This study aimed to clarify the effects of FK506 on the porcine mesenteric artery. Methods: The effects of FK506 on the changes in cytosolic Ca2+ concentration ([Ca2+]i) and force using fura-2 fluorometry were investigated in mesenteric arterial strips of the porcine small intestine. The effects of FK506 on the activity of voltage-dependent Ca2+ channels and receptor-operated Ca2+ channels using high K+ (118 mmol/L K+) depolarization and thromboxane A2 analog (U46619) stimulation were also examined. Results: FK506 inhibited the force development induced by 118 mmol/L K+ depolarization and 1 μmol/L U46619 stimulation in a concentration-dependent manner. The extent of inhibition of this contraction was greater than that of the K+-induced contraction, and its inhibitory potency was about 10-fold. FK506 (10 μmol/L) inhibited the increases in [Ca2+]i (24.9% ± 7.4%) and the force development (52.0% ± 5.6%) induced by 1 μmol/L U46619, respectively. Conclusions: FK506 induces arterial relaxation by decreasing [Ca2+]i. Pretreatment of a graft with FK506 may reduce the risk of vasospasm, ischemia-reperfusion injury, and thrombosis in small bowel transplantation.
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U2 - 10.1016/j.jpedsurg.2009.07.060
DO - 10.1016/j.jpedsurg.2009.07.060
M3 - Article
C2 - 20006018
AN - SCOPUS:71649105324
SN - 0022-3468
VL - 44
SP - 2322
EP - 2326
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
IS - 12
ER -