Dual effect of clonidine on isolated rabbit pulmonary arteries.
Clonidine, a partially selective agonist for alpha 2-adrenoceptors, has been increasingly used in anesthesia. Its direct effect on pulmonary arteries has not yet been clearly characterized. This in vitro study was performed to determine the vasoactive effects of clonidine on isolated rabbit pulmonary arteries. Responses of pulmonary artery rings from New Zealand white rabbits were assessed in the presence and absence of intact endothelium and with or without precontraction by norepinephrine (NE, 3 x 10(-6) M) or potassium chloride (KCl, 3 x 10(-2) M). Using tissue bath preparation, cumulative concentration response curves of clonidine were obtained at different concentrations (10(-8), 10(-7), 10(-6), 10(-5), 10(-4) M) after a period of stabilization. Clonidine caused vasoconstriction of isolated pulmonary arteries without any pretreatment. The magnitude of the constriction was dose related at lower concentrations and reached maximum of 300 g/g wet tissue when above 10(-6) M. On KCl-precontracted pulmonary arteries, clonidine caused significant dose-related vasoconstriction. On the NE-precontracted vessel rings, it elicited significant dose-dependent vasodilation up to 80% relaxation at 10(-4) M. All the above effects were endothelium independent. In conclusion, clonidine has dual endothelium-independent vasoactive effects, causing vasoconstriction on isolated rabbit pulmonary arteries, either untreated or precontracted with KCl, and vasodilation on those precontracted with NE. Clonidine may act as a competitive alpha-adrenoceptor blocking agent.
Lee
T S
TS
Department of Anesthesiology, Harbor-UCLA Medical Center, Torrance 90509-2910.
Hou
X
X
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D003000:Clonidine; D009638:Norepinephrine