Dichotomous effects of rosiglitazone in transplantation-induced systemic vasodilator dysfunction in rats
| Autor: | Flip A. Klatter, Mark Walther Boer, Heleen Rienstra, Jan-Luuk Hillebrands, Geanina Onuta, Jan Rozing, Anton J.M. Roks, Gerarda Navis |
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| Přispěvatelé: | Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Lifestyle Medicine (LM), Groningen Institute for Organ Transplantation (GIOT), Internal Medicine |
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Vasodilator Agents SMOOTH-MUSCLE-CELLS Vasodilation Organ transplantation endothelial dysfunction rosiglitazone Rats Inbred BN Internal medicine medicine Animals Transplantation Homologous rat Aorta Abdominal Endothelial dysfunction ENDOTHELIAL PROGENITOR CELLS Transplantation Vasomotor business.industry GAMMA-AGONIST ROSIGLITAZONE DIABETES-MELLITUS CORONARY STENT IMPLANTATION medicine.disease C-REACTIVE PROTEIN NONDIABETIC PATIENTS Rats smooth muscle cells Endothelial stem cell PPAR gamma Endocrinology surgical procedures operative MYOCARDIAL-INFARCTION Rats Inbred Lew Vasoconstriction PROLIFERATOR-ACTIVATED RECEPTORS Cardiology Thiazolidinediones PPAR-GAMMA Tunica Intima Rosiglitazone business medicine.drug |
| Zdroj: | Transplantation, 85(4), 582-588. LIPPINCOTT WILLIAMS & WILKINS Transplantation, 85(4), 582-588. Lippincott Williams & Wilkins |
| ISSN: | 1534-6080 0041-1337 |
| Popis: | Background. 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 PPAR gamma 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.Methods. Lewis abdominal aortic allografts were orthotopically transplanted into Brown Norway recipients that received either regular chow or chow containing rosiglitazone (similar to 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.Results. 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.Conclusions. 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. |
| Databáze: | OpenAIRE |
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