Role of Endothelin-1 in Microvascular Dysfunction Caused by Cyclosporin A

Coronary Endothelial Vasomotor Function and Vascular Remodeling in Heart Transplant Recipients Randomized for Tacrolimus or Cyclosporine Immunosuppression

“…The CyA also significantly increased ET-1 release by the capillaries, and Tac did not. As suggested in a subsequent in vitro study by the same group, ET-1, as a potent vasoconstrictive peptide and a proliferative factor of endothelial cells, is implicated in CyA-induced endothelial dysfunction (22). Our findings could verify these in vitro results.…”

Tacrolimus preserves vasomotor function and maintains vascular homeostasis

“…[1][2][3][4] Our group has shown that CsA treatment yields vasomotor dysfunction characterized by impairment in vasorelaxation and increased sensitivity to vasospasm as a result of changes in NO/ET regulation. [5][6][7] Although tacrolimus (Tac) has yet to demonstrate a major difference in rescuing the allograft from refractory rejection or preventing AV, the vascular effects appear more promising.…”

Nitric oxide/cytochrome P450 interactions in cyclosporin A-induced effects in the rat

“…NO is known to inhibit the expression, production, and activity of endothelin-1 [24], whereas NO inhibition increased endothelin-1 production [23]. It therefore appears that increased endothelin-1 production and prepro endothelin-1 expression after cyclosporin A treatment [25] can be accounted for by the diminution in NO production. As we have shown in our previous study that 20-HETE is the mediator of the vascular and tubular effects of endothelin-1 [20,26], it stands to reason that the increased 20-HETE production in cyclosporin A-treated animals [15,16] may be the consequence of increased endothelin-1 production.…”