Nickel inhibits urocortin-induced relaxation in the rat pulmonary artery

Urocortin relaxes rat Pulmonary arteries partly through a cyclic AMP-dependent but Ca2+ channel-independent mechanism. However, other participating mechanisms are relatively unknown. The present study was designed to examine whether the forward mode of Na+-Ca2+ 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-11alpha,9alpha-epoxymethanoprostaglandin F-2alpha (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 (Ni2+) chloride, a putative inhibitor of the Na+- Ca2+ 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+-Ca2+ exchanger. In contrast, the relaxant responses to atrial natriuretic peptide or forskolin were unaffected by Ni2+ or with removal of extracellular Na+. The present results provide indirect evidence suggesting that stimulation of Na+-Ca2+ exchangers may contribute to urocortin-induced endothelium-independent pulmonary artery relaxation. (C) 2004 Elsevier B.V. All rights reserved.