No abstract

Patients with EH have an altered profile of pro-and anti-inflammatory cytokines, consistent with monocyte activation in the circulation. The importance of these changes for the pathogenesis of EH and/or its secondary complications remains to be elucidated.

SUMMARYThe balance between pro-and anti-inflammatory cytokines has been implicated in the pathogenesis of infectious and auto-immune diseases, and its modulation has been proposed as a potential therapeutic target. The results reported in the present study show that modulators of the reninangiotensin system, such as the angiotensin-converting enzyme (ACE )-inhibitor captopril and the angiotensin II receptor type I antagonist valsartan, have potent inhibitory effects on the lipopolysaccharide (LPS )-stimulated production of pro-inflammatory cytokines tumour necrosis factor (TNF ) and interleukin-1 (IL-1) in vitro. The anti-inflammatory cytokine IL-1Ra is increased by captopril, whereas IL-6 production is decreased by valsartan. These effects are exerted mainly at high concentrations of the drugs. Administration of one dose of captopril or valsartan in therapeutic dosages to patients with essential hypertension did not influence LPS-stimulated production of cytokines by whole blood. In conclusion, despite inhibitory effects on proinflammatory cytokine production in vitro, it is unlikely that captopril or valsartan could be used in anticytokine therapeutic strategies in vivo.

Corresponding author: Professor P. Smits, Department of Phar macology, University of Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands Abbreviations: KATP channel, Adenosine-5 '-triphosphate-sen sitive potassium channel; SU, sulphonylurea; FBF, forearm blood flow; SNP, sodium nitroprusside; FVR, forearm vascular resistance; MAP, mean arterial pressure; NIDDM, non-insu lin-dependent diabetes mellitus.

Most patients with severe PTS had a combination of deep and superficial reflux. Reflux in the deep proximal veins contributes significantly to the PTS.