title: Cyclosporine A impairs norepinephrine-induced vascular contractility.
abstract: Usage of cyclosporine A (CsA) after kidney transplantation may be associated with development of nephrotoxicity and vasculopathy, but the mechanisms by which CsA causes vascular dysfunction are still under scrutiny. We established a transplantation model and investigated the effect of CsA on vascular contractility with the aid of a pressurized myograph in comparison with control and unilaterally nephrectomized rats. Results were correlated with mRNA expression studies of α- and β-adrenoreceptors, in mesenteric resistance arteries versus the thoracic aorta. Consequences of everolimus on functional properties as well as adrenoreceptor expression were also studied. CsA significantly downregulated expression of mesenteric adrenoreceptors, whereas no effect on aortic adrenoreceptors was seen. Administration of everolimus had no influence on mRNA adrenoreceptor expression in mesenteric resistance arteries. Furthermore, contractile responses of mesenteric resistance arteries to norepinephrine were markedly reduced after treatment with CsA, while there was no difference in contraction by endothelin. Everolimus did not alter the contractility response at all. In summary, norepinephrine-induced, but not endothelin-induced, contractile responses of mesenteric resistance arteries are blunted in CsA-treated rats. This finding was accompanied by a marked downregulation of adrenoreceptors in mesenteric resistance arteries and was limited to the usage of CsA.
authors.affiliation: Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany. tobias.bergler @ klinik.uni-regensburg.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Bergler
authors.forename: Markus
authors.initials: M
authors.lastname: Resch
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Reinhold
authors.forename: Christoph
authors.initials: C
authors.lastname: Birner
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Jungbauer
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Griese
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid
authors.forename: Bernhard
authors.initials: B
authors.lastname: Banas
authors.forename: Dierk
authors.initials: D
authors.lastname: Endemann
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D016572:Cyclosporine; D009638:Norepinephrine