Barium and Strontium Can Substitute for Calcium in Stimulating Nitric Oxide Production in the Endothelium of Canine Coronary Arteries

Abstract

We investigated whether Ba²⁺ and Sr²⁺ can substitute for Ca²⁺ in stimulating the nitric oxide (NO) production and cause relaxation in vascular smooth muscle. Ba²⁺ and Sr²⁺, like Ca²⁺, relaxed K⁺ -depolarized canine coronary arteries in the presence of diltiazem. The Ba²⁺- and Sr²⁺-induced relaxation was endothelium-dependent and was largely inhibited by N^G-monomethyl-L-arginine (L-NMMA) and N^G-nitro-L-arginine (L-NNA), but not by indomethacin. These cations increased cyclic GMP levels in the coronary artery to a similar extent, and the increment was completely abolished by L-NMMA. The relaxation induced by each cation was attenuated in the presence of a combination of propranolol, phentolamine and atropine, and L-NNA markedly inhibited any remaining relaxation. This indicates that these cations produce endothelium-dependent relaxation through NO production as well as the relaxation mediated by neurotrasmitters. The present study suggests that Ba²⁺ and Sr²⁺ can substitute for Ca²⁺ in the activation of the NO synthase pathway in the endothelium of canine coronary arteries.