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.

Nyckelord

Aged

Arginine/therapeutic use

Cyclooxygenase Inhibitors/*therapeutic use

Diclofenac/*therapeutic use

Endothelium; Vascular/*physiopathology

Female

Forearm/blood supply

Humans

Kidney Failure; Chronic/*drug therapy/*physiopathology

Male

Methacholine Chloride/diagnostic use

Middle Aged

Nitroprusside/diagnostic use

Regional Blood Flow/drug effects

Research Support; Non-U.S. Gov't

Vasodilation/*drug effects

Vasodilator Agents/diagnostic use

MEDICINE

MEDICIN

Publikations- och innehållstyp

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