Barium and strontium can substitute for calcium in stimulating nitric oxide production in the endothelium of canine coronary arteries.
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 Ba(2+)- and Sr(2+)-induced relaxation was endothelium-dependent and was largely inhibited by NG-monomethyl-L-arginine (L-NMMA) and NG-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 neurotransmitters. 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.