PMID- 21273094
OWN - NLM
STAT- MEDLINE
DCOM- 20110929
LR  - 20131121
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 30
IP  - 5
DP  - 2011 May
TI  - Tacrolimus preserves vasomotor function and maintains vascular homeostasis.
PG  - 583-8
LID - 10.1016/j.healun.2010.11.022 [doi]
AB  - BACKGROUND: Post-transplant immunosuppression is associated with endothelial 
      dysfunction that may lead to vasculopathy. We have previously demonstrated that 
      cyclosporine causes vascular dysfunction. In this we study examined the effect of 
      tacrolimus (Tac) in an identical model. METHODS: Lewis rats (n = 8 per group) 
      were injected with Tac (low, medium or high dose) or saline (Con) daily for 2 
      weeks. Segments of thoracic aorta (TAo) were assessed for endothelium-dependent 
      (Edep) and -independent (Eind) vasorelaxation (E(max)) and sensitivity to 
      endothelin (ET)-induced vasoconstriction (C(max)). ET(A) and ET(B) receptor (Rc) 
      expression levels were determined in TAo. Tumor necrosis factor-alpha (TNF-alpha) and 
      transforming growth factor-beta (TGF-beta) expression were determined in myocardial 
      (LV) tissue. Plasma ET levels and tissue oxidative injury were quantified by 
      enzyme-linked immunoassay. RESULTS: Tac did not impair Edep relaxation when 
      compared with Con (p = 0.69). Impairment of sodium nitroprusside-mediated Eind 
      vasorelaxation was noted with Tac (E(max): Con 69 +/- 2%, Tac high 54 +/- 2%; p = 
      0.0001), whereas no such impairment was seen with diltiazem-mediated Eind 
      vasorelaxation (p = 0.06). Tac decreased sensitivity to ET (C(max): Con 222 +/- 
      19%, Tac high 162 +/- 11%; p = 0.0002) and ET levels (Con 0.8 +/- 0.1 fmol/ml, Tac 
      0.4 +/- 0.1 fmol/ml; p = 0.02). Tac did not alter ET(A) Rc expression (p = 0.28), 
      but increased ET(B) Rc levels (p = 0.02). Oxidative injury was similar in both LV 
      (p = 0.43) and Ao (p = 0.73) tissue. Similarly, TNF-alpha expression (p = 0.16) was 
      not different between groups, whereas expression of TGF-beta demonstrated a 
      significant decrease with Tac treatment (p = 0.02). CONCLUSION: Our findings 
      suggests that tacrolimus has beneficial effects with respect to endothelial 
      function.
CI  - Copyright (c) 2011 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Tepperman, Elissa D
AU  - Tepperman ED
AD  - Heart Transplant Program, Peter Munk Cardiac Centre, University Health Network, 
      Toronto General Hospital, Toronto, Ontario, Canada.
FAU - Tumiati, Laura C
AU  - Tumiati LC
FAU - Ramzy, Danny
AU  - Ramzy D
FAU - Badiwala, Mitesh V
AU  - Badiwala MV
FAU - Sheshgiri, Rohit
AU  - Sheshgiri R
FAU - Prodger, Jessica L
AU  - Prodger JL
FAU - Ross, Heather J
AU  - Ross HJ
FAU - Rao, Vivek
AU  - Rao V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110126
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Receptor, Endothelin A)
RN  - 0 (Receptor, Endothelin B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vasodilator Agents)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/drug effects/physiology
MH  - Endothelium, Vascular/*drug effects/*physiology
MH  - Homeostasis/*drug effects/physiology
MH  - Immunosuppressive Agents/*pharmacology
MH  - Male
MH  - Models, Animal
MH  - Myocardium/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Receptor, Endothelin A/metabolism
MH  - Receptor, Endothelin B/metabolism
MH  - Tacrolimus/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vasodilation/drug effects/physiology
MH  - Vasodilator Agents/pharmacology
MH  - Vasomotor System/*drug effects/*physiology
EDAT- 2011/01/29 06:00
MHDA- 2011/10/01 06:00
CRDT- 2011/01/29 06:00
PHST- 2010/06/26 00:00 [received]
PHST- 2010/10/28 00:00 [revised]
PHST- 2010/11/09 00:00 [accepted]
PHST- 2011/01/29 06:00 [entrez]
PHST- 2011/01/29 06:00 [pubmed]
PHST- 2011/10/01 06:00 [medline]
AID - S1053-2498(10)00774-6 [pii]
AID - 10.1016/j.healun.2010.11.022 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2011 May;30(5):583-8. doi: 10.1016/j.healun.2010.11.022. 
      Epub 2011 Jan 26.