Lack of role of endothelium-derived relaxing factor in effects of alpha-adrenergic agonists in cutaneous veins in humans.
In some blood vessels, the alpha 2-adrenergic agonist clonidine simultaneously activates vasoconstrictive alpha-adrenoceptors on smooth muscle cells and endothelial alpha 2-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 alpha 1-antagonist labetalol. However, in veins preconstricted with the full alpha 1-agonist phenylephrine, clonidine induced venodilation, suggesting that clonidine is a partial agonist at venous alpha 1-adrenoceptors. In conclusion, we found no evidence for endothelial alpha 2-adrenoceptor-mediated release of EDRF in human hand veins. The results further suggest that postjunctional alpha 1-adrenoceptors participate in clonidine-induced venoconstriction in humans.
Haefeli
W E
WE
Department of Medicine, Stanford University Medical Center, California 94305-5113.
Srivastava
N
N
Kongpatanakul
S
S
Blaschke
T F
TF
Hoffman
B B
BB
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006225:Hand / Q000098:blood supply; D006801:Humans; D007741:Labetalol / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D012867:Skin / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects; D014680:Veins / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000804:Angiotensin II; D009569:Nitric Oxide; D006152:Cyclic GMP; D007741:Labetalol; D001920:Bradykinin; D008751:Methylene Blue