Reduced endothelin-1- and nitric oxide-mediated arteriolar tone in hypertensive renal transplant recipients.
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.
Passauer
Jens
J
Division of Nephrology, Department of Medicine, University Hospital Carl Gustav Carus, Dresden, Germany. passauer@rcs.urz.tu-dresden.de
Lässig
Grit
G
Büssemaker
Eckhart
E
Pistrosch
Frank
F
Gross
Peter
P
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
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