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The (R)-enantiomer of the 6-chromanol derivate SUL-121 improves renal graft perfusion via antagonism of the α1-adrenoceptor.


ABSTRACT: SUL-compounds are protectants from cold-induced ischemia and mitochondrial dysfunction. We discovered that adding SUL-121 to renal grafts during warm machine reperfusion elicits a rapid improvement in perfusion parameters. Therefore, we investigate the molecular mechanisms of action in porcine intrarenal arteries (PIRA). Porcine kidneys were stored on ice overnight and perfusion parameters were recorded during treatment with SUL-compounds. Agonist-induced vasoconstriction was measured in isolated PIRA after pre-incubation with SUL-compounds. Receptor binding and calcium transients were assessed in α1-adrenoceptor (α1-AR) transgenic CHO cells. Molecular docking simulation was performed using Schrödinger software. Renal pressure during warm reperfusion was reduced by SU

SUBMITTER: Nakladal D 

PROVIDER: S-EPMC6327096 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature