Nickel inhibits urocortin-induced relaxation in the rat pulmonary artery

Abstract

Urocortin relaxes rat pulmonary arteries partly through a cyclic AMP-dependent but Ca 2+ channel-independent mechanism. However, other participating mechanisms are relatively unknown. The present study was designed to examine whether the forward mode of Na +–Ca 2+ exchangers play a role in the relaxant responses to urocortin in isolated rat small pulmonary arteries. Endothelium-denuded rings were mounted on small vessel myographs for measurement of changes in isometric tension. Urocortin inhibited 9,11-dideoxy-11α,9α-epoxy-methanoprostaglandin F 2α (U46619)-induced contraction in a concentration-dependent manner and this inhibition was reversed by astressin, a corticotropin-releasing factor receptor antagonist. Micromolar concentrations of nickel (Ni 2+) chloride, a putative inhibitor of the Na +–Ca 2+ exchanger, reduced the relaxant responses to urocortin. Urocortin-induced relaxation was abolished in a Na +-free solution, a condition that eliminates influence of the forward mode of Na +–Ca 2+ exchanger. In contrast, the relaxant responses to atrial natriuretic peptide or forskolin were unaffected by Ni 2+ or with removal of extracellular Na +. The present results provide indirect evidence suggesting that stimulation of Na +–Ca 2+ exchangers may contribute to urocortin-induced endothelium-independent pulmonary artery relaxation.