Cyclooxygenase inhibition improves endothelium-dependent vasodilatation in patients with chronic renal failure.
BACKGROUND
Some studies have demonstrated beneficial effects of L-arginine as a substrate for nitric oxide synthesis, and diclofenac as an inhibitor of cyclooxygenase (COX)-derived vasoconstrictive agents on vascular responses in humans during several pathological conditions. The aim of the present study was to investigate the acute effects of L-arginine and diclofenac on endothelium-dependent vasodilatation (EDV) and endothelium-independent vasodilatation (EIDV) in patients with chronic renal failure (CRF).


METHODS
Effects of L-arginine and diclofenac on EDV and EIDV were measured in 15 patients with CRF and in 15 healthy controls by means of forearm blood flow measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (2 and 4 micro g/min evaluating EDV) and sodium nitroprusside (5 and 10 micro g/min evaluating EIDV).


RESULTS
L-Arginine infusion increased methacholine-induced vasodilatation both in patients with CRF and healthy controls. Diclofenac infusion increased methacholine-induced vasodilatation only in patients with CRF. There was no significant change in nitroprusside-induced vasodilatation after L-arginine and diclofenac infusions both in patients with CRF and healthy controls.


CONCLUSIONS
These results suggest that COX inhibition reduces the levels of a prostanoid-derived vasoconstrictive agent contributing to the impaired EDV in patients with CRF, while in this age group L-arginine improves EDV regardless of renal function.
Annuk
Margus
M
Department of Medical Science, University Hospital, Uppsala, Sweden. Margus.Annuk@medsci.uu.se
Fellström
Bengt
B
Lind
Lars
L
D000368:Aged; D001120:Arginine / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004008:Diclofenac / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009599:Nitroprusside; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents
D016861:Cyclooxygenase Inhibitors; D014665:Vasodilator Agents; D016210:Methacholine Chloride; D004008:Diclofenac; D009599:Nitroprusside; D001120:Arginine