Endothelin plays an important role in the endothelium-dependent vasodilatation in the human forearm.
Endothelium-dependent vasodilatation (EDV) in humans has been evaluated mainly 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 vasoconstrictor endothelin in this model has not been investigated.


METHODS
Ten male hypertensive and seven male normotensive subjects were subjected to measurements of forearm blood flow (FBF) by venous occlusion plethysmography during local intra-arterial infusion of metacholine (4 microg/min) or nitroprusside (10 microg/min). In parallel, forearm venous plasma endothelin (ir-ET) was determined.


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 hypertensive subjects and 5.1 times the baseline level (2.7+/-3.0 ml/min/100 ml tissue) for both drugs in the normotensive subjects. None of the drugs induced any 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.


CONCLUSIONS
Muscarinic-receptor-agonist-stimulated vasodilatation in the human forearm, thought mainly to reflect NO synthesis, was inversely related to the change in endothelin levels, suggesting an important role for this endothelium-derived vasoconstrictor in this model of EDV.
Sarabi
M
M
Department of Internal Medicine, University Hospital of Uppsala, Sweden.
Millgård
J
J
Hägg
A
A
Ridefelt
P
P
Henriksson
J
J
Lind
L
L
D000328:Adult; D000368:Aged; D016232:Endothelins / Q000097:blood / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D016232:Endothelins; D016210:Methacholine Chloride; D009569:Nitric Oxide