title: Reduced endothelin-1- and nitric oxide-mediated arteriolar tone in hypertensive renal transplant recipients.
abstract: BACKGROUND
  The prevalence of hypertension is high in renal transplant recipients. It has been suggested that calcineurin inhibitors (CI) contribute to the development of post-transplant hypertension by stimulating endothelin (ET-1)-mediated and/or reducing nitric oxide (NO)-mediated vascular tone.
  
  
  METHODS
  We tested this hypothesis using 2 groups of renal transplant recipients [normotensive patients without a need for antihypertensive medication (Normo-Tx), and hypertensive patients requiring antihypertensives (Hyper-Tx)] in the presence of CI-based immunosuppression. In addition, we studied matched control subjects (C). BQ 123 (ET-A receptor antagonist), BQ123 + BQ788 (ET-A/B-receptor antagonist), ET-1, L-NMMA (NO-synthase inhibitor), acetylcholine (ACH; endothelium-dependent vasodilator), glyceroltrinitrate (GTN, NO donor), and norepinephrine (NE, endothelium-independent vasoconstrictor) were infused into the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography.
  
  
  RESULTS
  Endothelium-independent vasomotion in response to GTN and NE was similar in all groups. Vascular responses to selective and combined blockade of ET receptors in both Normo-Tx and Hyper-Tx did not exceed those of C. In fact, we observed a significantly lower increase in FBF after BQ 123 (P= 0.03), as well as after BQ 123/788 (P= 0.03) in Hyper-Tx compared with Normo-Tx. This was associated with an increased vascular sensitivity to exogenous ET-1 in Hyper-Tx compared with Normo-Tx (P= 0.04). Vasoconstriction after L-NMMA was reduced in Hyper-Tx compared with Normo-Tx (P= 0.015), while the response to ACH was reduced in both groups of Tx patients to a similar degree (P= 0.005 vs. C).
  
  
  CONCLUSIONS
  Our results do not support a major role for the vascular endothelin system in the hypertension of renal transplant recipients, whereas deficient baseline NO production may be a contributing factor.
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Carl Gustav Carus, Dresden, Germany. passauer@rcs.urz.tu-dresden.de
authors.forename: Jens
authors.initials: J
authors.lastname: Passauer
authors.forename: Grit
authors.initials: G
authors.lastname: Lässig
authors.forename: Eckhart
authors.initials: E
authors.lastname: Büssemaker
authors.forename: Frank
authors.initials: F
authors.lastname: Pistrosch
authors.forename: Peter
authors.initials: P
authors.lastname: Gross
mesh_terms: D000328:Adult; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000187:drug effects; D065095:Calcineurin Inhibitors; D016022:Case-Control Studies; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D005542:Forearm; D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology* / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D065095:Calcineurin Inhibitors; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide