Tacrolimus preserves vasomotor function and maintains vascular homeostasis

Elissa D. Tepperman, Laura C. Tumiati, Danny Ramzy, Mitesh V. Badiwala, Rohit Sheshgiri, Jessica Prodger, Heather J. Ross, Vivek Rao

Research output: Contribution to journalArticle

Abstract

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 (Cmax). ETA and ETB receptor (Rc) expression levels were determined in TAo. Tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) 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 nitroprussidemediated Eind vasorelaxation was noted with Tac (Emax: 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 (Cmax: 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 ETA Rc expression (p = 0.28), but increased ETB Rc levels (p = 0.02). Oxidative injury was similar in both LV (p = 0.43) and Ao (p = 0.73) tissue. Similarly, TNF-α expression (p = 0.16) was not different between groups, whereas expression of TGF-β demonstrated a significant decrease with Tac treatment (p = 0.02). Conclusion: Our findings suggests that tacrolimus has beneficial effects with respect to endothelial function.

Original languageEnglish (US)
Pages (from-to)583-588
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume30
Issue number5
DOIs
StatePublished - May 1 2011
Externally publishedYes

Fingerprint

Tacrolimus
Blood Vessels
Homeostasis
Endothelins
Vasodilation
Thoracic Aorta
Transforming Growth Factor beta
Endothelium
Tumor Necrosis Factor-alpha
Diltiazem
Wounds and Injuries
Vasoconstriction
Immunoenzyme Techniques
Immunosuppression
Cyclosporine
Sodium
Transplants

Keywords

  • endothelial function
  • endothelin
  • immunosuppression
  • nitric oxide
  • tacrolimus
  • transplantation
  • vasculopathy

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

Tepperman, E. D., Tumiati, L. C., Ramzy, D., Badiwala, M. V., Sheshgiri, R., Prodger, J., ... Rao, V. (2011). Tacrolimus preserves vasomotor function and maintains vascular homeostasis. Journal of Heart and Lung Transplantation, 30(5), 583-588. https://doi.org/10.1016/j.healun.2010.11.022

Tacrolimus preserves vasomotor function and maintains vascular homeostasis. / Tepperman, Elissa D.; Tumiati, Laura C.; Ramzy, Danny; Badiwala, Mitesh V.; Sheshgiri, Rohit; Prodger, Jessica; Ross, Heather J.; Rao, Vivek.

In: Journal of Heart and Lung Transplantation, Vol. 30, No. 5, 01.05.2011, p. 583-588.

Research output: Contribution to journalArticle

Tepperman, ED, Tumiati, LC, Ramzy, D, Badiwala, MV, Sheshgiri, R, Prodger, J, Ross, HJ & Rao, V 2011, 'Tacrolimus preserves vasomotor function and maintains vascular homeostasis', Journal of Heart and Lung Transplantation, vol. 30, no. 5, pp. 583-588. https://doi.org/10.1016/j.healun.2010.11.022
Tepperman, Elissa D. ; Tumiati, Laura C. ; Ramzy, Danny ; Badiwala, Mitesh V. ; Sheshgiri, Rohit ; Prodger, Jessica ; Ross, Heather J. ; Rao, Vivek. / Tacrolimus preserves vasomotor function and maintains vascular homeostasis. In: Journal of Heart and Lung Transplantation. 2011 ; Vol. 30, No. 5. pp. 583-588.
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abstract = "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 (Cmax). ETA and ETB receptor (Rc) expression levels were determined in TAo. Tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) 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 nitroprussidemediated Eind vasorelaxation was noted with Tac (Emax: 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 (Cmax: 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 ETA Rc expression (p = 0.28), but increased ETB Rc levels (p = 0.02). Oxidative injury was similar in both LV (p = 0.43) and Ao (p = 0.73) tissue. Similarly, TNF-α expression (p = 0.16) was not different between groups, whereas expression of TGF-β demonstrated a significant decrease with Tac treatment (p = 0.02). Conclusion: Our findings suggests that tacrolimus has beneficial effects with respect to endothelial function.",
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