Dichotomous Effects of Rosiglitazone in Transplantation-Induced Systemic Vasodilator Dysfunction in Rats

Transplantation-induced systemic endothelial dysfunction causes severe cardiovascular morbidity and mortality after transplantation. Interventions that improve systemic endothelial function after transplantation and furthermore reduce intragraft vascular dysfunction might improve graft and patient s...

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Bibliographic Details
Published in:	Transplantation Vol. 85; no. 4; pp. 582 - 588
Main Authors:	ONUTA, Geanina, HILLEBRANDS, Jan-Luuk, RIENSTRA, Heleen, WALTHER BOER, Mark, KLATTER, Flip A, NAVIS, Gerjan, RAZING, Jan, ROKS, Anton J. M
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott 27-02-2008
Subjects:	Animals Aorta, Abdominal - drug effects Aorta, Abdominal - pathology Aorta, Abdominal - transplantation Biological and medical sciences Fundamental and applied biological sciences. Psychology Fundamental immunology Male Medical sciences Rats Rats, Inbred BN Rats, Inbred Lew Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Thiazolidinediones - therapeutic use Tissue, organ and graft immunology Transplantation, Homologous - adverse effects Tunica Intima - drug effects Tunica Intima - pathology Vasoconstriction - drug effects Vasoconstriction - physiology Vasodilation - drug effects Vasodilator Agents - therapeutic use Vasodilator agent Rat Rodentia Thiazolidinedione derivatives Systemic Transplantation Homotransplantation Vertebrata Hypoglycemic agent Mammalia Treatment Dysfunction Surgery Animal Rosiglitazone Graft Disseminated
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Summary:	Transplantation-induced systemic endothelial dysfunction causes severe cardiovascular morbidity and mortality after transplantation. Interventions that improve systemic endothelial function after transplantation and furthermore reduce intragraft vascular dysfunction might improve graft and patient survival. Treatment with the PPARgamma agonist rosiglitazone is an intervention that potentially fulfills these criteria. In this study, we determined the effect of rosiglitazone treatment on transplantation-induced endothelial dysfunction and vasomotor activity in an experimental model for chronic transplant dysfunction in rats. Lewis abdominal aortic allografts were orthotopically transplanted into Brown Norway recipients that received either regular chow or chow containing rosiglitazone (approximately 4.2 mg/day). Endothelium-dependent (response to metacholine) and total (response to sodium nitrite) vasodilatory responses were determined in autologous thoracic aortic rings using an ex vivo organ bath setup. Measurements were performed 8 weeks after transplantation. Aortic allografting induced systemic endothelial dysfunction as measured by reduced endothelium-dependent vasodilation in the recipient's vascular system. Rosiglitazone treatment restored endothelium-dependent vasodilatory responses to pretransplantation levels. However, rosiglitazone treatment reduced the total dilatory response despite normalized endothelial function, indicating impairment of vascular smooth muscle cell vasomotor activity. Rosiglitazone treatment after allogeneic transplantation restores endothelial function but impairs vascular smooth muscle cell vasomotor activity. This dichotomous effect of rosiglitazone might impede use of rosiglitazone after organ transplantation since this potentially increases cardiovascular risk despite improved endothelial cell function.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0041-1337 1534-6080
DOI:	10.1097/TP.0b013e3181639c83