LACK OF ROLE OF ENDOTHELIUM-DERIVED RELAXING FACTOR IN EFFECTS OF ALPHA-ADRENERGIC AGONISTS IN CUTANEOUS VEINS IN HUMANS

In some blood vessels, the alpha2-adrenergic agonist clonidine simultaneously activates vasoconstrictive alpha-adrenoceptors on smooth muscle cells and endothelial alpha2-adrenoceptors mediating release of endothelium-derived relaxing factor (EDRF), with the net vascular response representing a balance between these two counteracting pathways. To investigate whether clonidine's modest constrictor effect in human veins is due to simultaneous release of EDRF, the dorsal hand vein compliance technique was used to measure vascular responses in healthy volunteers. Clonidine-induced venoconstriction was not potentiated by methylene blue, an inhibitor of EDRF-mediated relaxation. After preconstriction with angiotensin II, clonidine did not cause venodilation but rather promoted further constriction, which could be reversed by the alpha1-antagonist labetalol. However, in veins preconstricted with the full alpha1-agonist phenylephrine, clonidine induced venodilation, suggesting that clonidine is a partial agonist at venous alpha1-adrenoceptors. In conclusion, we found no evidence for endothelial alpha2-adrenoceptor-mediated release of EDRF in human hand veins. The results further suggest that postjunctional alpha1-adrenoceptors participate in clonidine-induced venoconstriction in humans.