Alpha2C-adrenoceptors play a prominent role in sympathetic constriction of porcine pulmonary arteries

Enhanced pulmonary vasoconstriction in response to injuries of the central nervous system and hypoxia result in pulmonary edema due to increased sympathetic activation. This study aimed to characterize α2-adrenoceptor (AR)-mediated responses in porcine pulmonary arteries. α2-AR-mediated vasoconstriction was studied using a tissue bath protocol. α2-AR protein was determined by Western blotting. UK14304 (α2-AR agonist) elicited only a slight contraction in pulmonary arteries compared to veins. Verapamil (voltage-operated Ca2+ channel blocker), 2-APB (store-operated Ca2+ channel inhibitor), and P1075 (KATP channel opener) induced a marked decrease of the basal tone in veins, but not in arteries. The UK14304-induced contraction in arteries was enhanced by (S)-(−)-Bay K 8644 (L-type Ca2+ channel activator), N ω-nitro-l-arginine methyl ester hydrochloride (L-NAME, eNOS inhibitor), and (S)-(−)-Bay K 8644 plus L-NAME to the same extent. Endothelium denudation failed to affect the UK14304 response. (S)-(−)-Bay K 8644 did not increase the maximal noradrenaline (non-selective α-AR agonist) or phenylephrine (α1-AR agonist) response. The rightward shift of the concentration–response curve to noradrenaline by prazosin (α1-AR antagonist) plus (S)-(−)-Bay K 8644 was smaller and non-parallel compared to that in the presence of prazosin alone. UK14304 responses were inhibited by MK912 (α2C-AR antagonist). Affinity of MK912 (pA2 9.76) and Western blotting analysis argue for an involvement of α2C-ARs in noradrenaline-induced contraction of pulmonary arteries. It is concluded that postjunctional α2C-ARs predominantly mediate contraction in porcine pulmonary arteries when the cytosolic Ca2+ concentration is elevated. α2C-AR antagonists may be beneficial in the treatment of pulmonary edema.