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Two good reasons for an angiotensin-II type 1 receptor blockade with losartan after cardiac transplantation: reduction of incidence and severity of transplant vasculopathy

  • Original Article
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Transplant International

Abstract

Despite considerable progress in immunosuppressive therapy, the incidence and severity of transplant vasculopathy (TVP) after cardiac transplantation have not declined. The renin–angiotensin system (RAS) plays a pivotal role in the proliferation of vascular smooth muscle cells (VSMCs) contributing to TVP. We compared the effects of an angiotensin-II blocker, losartan (AT1 blocker), and an angiotensin-converting enzyme (ACE) inhibitor, enalapril, on the incidence of diseased vessels and the severity of experimental TVP in the Lewis-to-Fischer rat heterotopic heart transplantation model. Recipients were randomly divided into six groups, group 1: no therapy, group 2: 3 mg/kg per day cyclosporine (CyA) s.c., group 3: CyA and 10 mg/kg per day losartan p.o., group 4: CyA and 40 mg/kg per day enalapril p.o., and groups 5 and 6: as groups 3 and 4, but additionally pre-treated with losartan or enalapril 7 days prior to transplantation. Eighty days after grafting, we assessed the incidence and severity of TVP, expressed as percentage of diseased vessels and mean vessel occlusion (MVO), by digitizing morphometry. CyA and CyA/enalapril post-treatment significantly reduced MVO, compared with controls, but not the incidence. Additional reduction of MVO was achieved in CyA/enalapril pre-treatment and both CyA/losartan pre- and post-treatment groups when compared with CyA and untreated controls. However, only losartan post-treatment in combination with CyA reduced both incidence and MVO. Our results validate the important role of the RAS in neointimal proliferation after cardiac transplantation. Losartan appears to be superior to enalapril in preventing TVP after experimental cardiac transplantation. Therefore, AT1 blockade with losartan might be a therapeutic option for the prevention of TVP in human heart recipients.

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Authors and Affiliations

  1. Experimental Heart Transplant Group, Am See 76, 04668 Parthenstein, Germany

    Markus H. C. Richter, Heike R. Richter & Hans Georg Olbrich

  2. Heart Center Leipzig, University of Leipzig, Leipzig, Germany

    Markus H. C. Richter & Friedrich Wilhelm Mohr

  3. 2nd Department of Internal Medicine, St. Elisabeth and St. Barbara Hospital, Halle, Germany

    Hans Georg Olbrich

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  1. Markus H. C. Richter
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  2. Heike R. Richter
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  3. Hans Georg Olbrich
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  4. Friedrich Wilhelm Mohr
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Correspondence to Markus H. C. Richter.

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Richter, M.H.C., Richter, H.R., Olbrich, H.G. et al. Two good reasons for an angiotensin-II type 1 receptor blockade with losartan after cardiac transplantation: reduction of incidence and severity of transplant vasculopathy. Transpl Int 16, 26–32 (2003). https://doi.org/10.1007/s00147-002-0506-x

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  • DOI: https://doi.org/10.1007/s00147-002-0506-x

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