Role of Endothelium and Adventitia on Eugenol-Induced Relaxation of Rabbit Ear Artery Precontracted by Histamine.

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Eugenol (≤0.1 mM) inhibited the contractions induced by various stimulants, such as 90 mM extracellular K+ solution ([K+] 0), histamine and noradrenaline in the rabbit ear artery. Inhibitory actions of eugenol occurred in a concentration-dependent manner, however, eugenol more dominantly inhibited the histamine-induced contraction than those induced by either 90 mM [K+] 0 solution or noradrenaline. Removal of both endothelium and adventitia did not change the inhibitory actions of eugenol on the 90 mM [K+] 0- and noradrenaline-induced contractions, however, attenuated those on the histamine-induced contraction. Chlorphenylamine abolished the histamine-induced contraction, but neither cimetidine, ranitidine nor thioperamide modified the eugenol actions on the contractions induced by histamine. Pretreatment with nitric oxide syntheses inhibitor NG-nitro-L-arginine (LNNA;100μM), but not soluble guanylate cyclase inhibitor methylene blue (MB;10μM), prevented endothelium/adventitia-dependent augmentation of the eugenol-induced relaxation on the histamine-induced contraction. When an intact tissue, but not an endothelium/ adventitia-denuded tissue, was placed at the up-stream close to the other denuded preparation (test preparation), histamine-induced contraction observed in the test preparation tended to be augmented. Similarly, eugenol-induced relaxation was also augmented by the same treatment.<BR>Eugenol (0.3 mM) inhibited the excitatory junction potentials (EJPs) without hyperpolarization of the membrane. However, a high concentration of eugenol (1 mM) slightly hyperpolarized the membrane (ca. 5 mV). No transient enhancement of amplitude of EJP was recorded.<BR>These results suggest that eugenol may inhibit the histamine-induced muscle contraction directly, and the inhibition is augemented by the adventitia and endothelium partly by vasoactive substances, which were released from the adventitia/endothelium-derived substances in rabbit ear artery.

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