Dual Effect of Clonidine on Isolated Rabbit Pulmonary Arteries

¹ From the Department of Anesthesiology, Harbor-UCLA Medical Center, Torrance, Calif.

Clonidine, a partially selective agonist for 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, 3x10⁶M) or potassium chloride (KCl, 3x10²M). Using tissue bath preparation, cumulative concentration response curves of clonidine were obtained at different concentrations (10⁸, 10⁷, 10⁶, 10⁵ 10⁴M) 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 10⁶M. On KCl-precontracted pulmonary arteries, clonidine caused significant dose-related vasoconstriction. On the NE-precontracted vessel rings, it elicited significant dosedependent vasodilation up to 80% relaxation at 10⁴M. 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 -adrenoceptor blocking agent.

Key Words: clonidine • pulmonary vasoconstrictor • pulmonary vasodilator

Submitted on October 19, 1993
Accepted on May 26, 2007