Endothelin plays an important role in the endothelium-dependent vasodilatation in the human forearm

Endothelium-dependent vasodilatation (EDV) in humans has been evaluated mai nly by local infusion of a muscarinic-receptor agonists in the forearm. It has been postulated that the function of the vasodilator nitric oxide (NO) can be evaluated with this technique. However, the role of the vasoconstric tor endothelin in this model has not been investigated. Methods: Ten male h ypertensive and seven male normotensive subjects were subjected to measurem ents of forearm blood flow (FBF) by venous occlusion plethysmography during local intra-arterial infusion of metacholine (4 mu g/min) or nitroprusside (10 mu g/min). In parallel, forearm venous plasma endothelin (ir-ET) was d etermined. Results: Metacholine and nitroprusside increased FBF 2.3 and 2.2 times the baseline level (6.6+/-2.8 SD ml/min/100 ml tissue) in hypertensi ve subjects and 5.1 times the baseline level (2.7+/-3.0 ml/min/100 mi tissu e) for both drugs in the normotensive subjects. None of the drugs induced a ny significant changes in ir-ET levels in any of the groups (baseline 1.5+/ -0.4 pmol/l in hypertensive and 1.1+/-1.2 pmol/l in normotensive subjects). However, in the hypertensive subjects, the individual change in venous ir- ET levels during infusion with metacholine, but not with nitroprusside, was inversely related to the degree of vasodilatation induced by this agent (r = -0.71, p<0.02). A similar correlation coefficient (r = -0.69) was found in healthy subjects. Conclusion: Muscarinic-receptor-agonist-stimulated vas odilatation in the human forearm, thought mainly to reflect NO synthesis, w as inversely related to the change in endothelin levels, suggesting an impo rtant role for this endothelium-derived vasoconstrictor in this model of ED V.