Direct vasodilative effect of FK506 on porcine mesenteric artery in small bowel transplantation.
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 Ca(2+) concentration ([Ca(2+)]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 Ca(2+) channels and receptor-operated Ca(2+) channels using high K(+) (118 mmol/L K(+)) depolarization and thromboxane A(2) analog (U46619) stimulation were also examined.


RESULTS
FK506 inhibited the force development induced by 118 mmol/L K(+) depolarization and 1 micromol/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 micromol/L) inhibited the increases in [Ca(2+)]i (24.9% +/- 7.4%) and the force development (52.0% +/- 5.6%) induced by 1 micromol/L U46619, respectively.


CONCLUSIONS
FK506 induces arterial relaxation by decreasing [Ca(2+)]i. Pretreatment of a graft with FK506 may reduce the risk of vasospasm, ischemia-reperfusion injury, and thrombosis in small bowel transplantation.
Akiyoshi
Junko
J
Department of Pediatric Surgery, Reproductive and Developmental Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Ieiri
Satoshi
S
Nakatsuji
Takanori
T
Taguchi
Tomoaki
T
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D016257:Fura-2; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007421:Intestine, Small / Q000098:blood supply / Q000637:transplantation*; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control; D013552:Swine; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D015220:Calcium Channels; D007166:Immunosuppressive Agents; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium; D016257:Fura-2; D016559:Tacrolimus