Norepinephrine-induced contraction of isolated rabbit bronchial artery: Role of α₁- and α₂-adrenoceptor activation

The contractile effect of norepinephrine (NE) on isolated rabbit bronchial artery rings (150-300 μm in diameter) and the role of α₁- and α₂-adrenoceptors (AR) on smooth muscle and endothelium were studied. In intact arteries, NE increased tension in a dose-dependent manner, and the sensitivity for NE was further increased in the absence of endothelium. In intact but not in endothelium-denuded arteries, the response to NE was increased in the presence of both indomethacin (Indo; cyclooxygenase inhibitor) and N(G)-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthase inhibitor], indicating that two endothelium-derived factors, NO and a prostanoid, modulate the NE-induced contraction. The α₁-AR antagonist prazosin shifted the NE dose-response curve to the right, and phenylephrine (α₁-AR agonist) induced a dose-dependent contraction that was potentiated by L-NAME or removal of the endothelium. The sensitivity to NE was increased slightly by the (α₂-AR antagonists yohimbine and idazoxan, and this effect was abolished by Indo or removal of the endothelium. Similarly, contractions induced by UK-14304 (α₂-AR agonist) were potentiated by Indo or removal of the endothelium. These results suggest that NE-induced contraction is mediated through activation of α₁- and α₂-ARs on both smooth muscle and endothelium. Activation of the α₁- and α₂-ARs on the smooth muscle causes contraction, whereas activation of the endothelial α₁- and α₂-ARs induces relaxation through release of NO (α₁-ARs) and a prostanoid (α₂-ARs).