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

Florian Jantschak, Heinz H Pertz

Index: Naunyn Schmiedebergs Arch. Pharmacol. 385(6) , 595-603, (2012)

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Abstract

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 α(2)-adrenoceptor (AR)-mediated responses in porcine pulmonary arteries. α(2)-AR-mediated vasoconstriction was studied using a tissue bath protocol. α(2)-AR protein was determined by Western blotting. UK14304 (α(2)-AR agonist) elicited only a slight contraction in pulmonary arteries compared to veins. Verapamil (voltage-operated Ca(2+) channel blocker), 2-APB (store-operated Ca(2+) channel inhibitor), and P1075 (K(ATP) 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 Ca(2+) 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 (α(1)-AR agonist) response. The rightward shift of the concentration-response curve to noradrenaline by prazosin (α(1)-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 (α(2C)-AR antagonist). Affinity of MK912 (pA(2) 9.76) and Western blotting analysis argue for an involvement of α(2C)-ARs in noradrenaline-induced contraction of pulmonary arteries. It is concluded that postjunctional α(2C)-ARs predominantly mediate contraction in porcine pulmonary arteries when the cytosolic Ca(2+) concentration is elevated. α(2C)-AR antagonists may be beneficial in the treatment of pulmonary edema.