gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Mycophenolate mofetil reduces blood pressure and proteinuria in salt-loaded SHRSP

Mycophenolat mofetil reduziert Blutdruck und Proteinurie in salzbelasteten SHRSP

Meeting Abstract (Hypertonie 2004)

Suche in Medline nach

  • D. Endemann - Universität Regensburg
  • R.M. Touyz - Clinical Resarch Institute of Montreal (Montreal, Cdn)
  • E.L. Schiffrin - Universität Regensburg (Regensburg, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP25

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Veröffentlicht: 10. August 2005

© 2005 Endemann et al.
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We tested the hypothesis that proteinuria and further blood pressure elevation in salt treated stroke-prone spontaneously hypertensive rats (SHRSP) is, at least in part, dependent on renal inflammation. Mycophenolate mofetil (MF) inhibits the de novo pathway of guanosine nucleotide synthesis, on which T- and B-lymphocytes are critically dependent. We choose this immunosuppressive therapy because in contrast to other immunomodulating agents it does not aim at intracellular signaling events (e.g. calcineurin inhibitors), prostaglandine synthesis (e.g. non-steroidal-antiinflammatory-agents), or steroid receptors, which directly can influence blood pressure. 10-week old SHRSP and normotensive controls (WKY) were treated for 5 weeks with or without MF (30mg/kg/day in drinking water). SHRSP were fed a high salt diet (4% NaCl chow). Blood pressure was assessed by tail cuff throughout the experiment and additionally by radiotelemetry at the end of the study. Urine was collected at the end of the experiment in metabolic cages. Small resistance arteries were studied on a pressurized myograph. MF blunted (203±6 vs. 243±12 mmHg, P<0.001) blood pressure elevation in salt-loaded SHRSP but had no effect in WKY (128±4 and 128±2 mmHg). Vascular properties were not improved by MF in salt-loaded SHRSP and in WKY as evidenced by media to lumen ratio and wall mechanical properties. Endothelial function was further impaired (P<0.05) in salt-loaded SHRSP treated with MF. 24-hour protein excretion was decreased by MF in salt-treated SHRSP (35±5 vs. 67±10 mg/24h, P<0.05) but not in WKY (50±2 and 46±6 mg/24h). In conclusion, MF prevented blood pressure rise and proteinuria in salt-loaded SHRSP without beneficial effect on the vasculature. Thus, blood pressure reduction through MF could be due to a protective effect on the kidney.