Barium decreases endothelium-dependent smooth muscle responses to transient but not to more prolonged acetylcholine applications

The influence of inhibiting the inward rectifier and Na/K pump on endotheli um-dependent hyperpolarizations in smooth muscle cells of the mesenteric ar tery was investigated. Membrane potential was measured with microelectrodes , and the influence of low concentrations of Ba2+ (30 mu M) and of high con centrations of ouabain (0.5 mM) on smooth muscle hyperpolarization elicited by prolonged or by transient exposure to acetylcholine (ACh, 3x10(-7) M) w as assessed in the continuous presence of NC-nitro-L-arginine (100 mu M) an d indomethacin (50 mu M). Pre-exposure to Ba2+ did not inhibit the magnitud e of smooth muscle cell hyperpolarization induced by ACh superfusion, but s ignificantly slowed its onset and time course. The membrane potential respo nse to transient ACh applications, however, was impaired. After combined Ba 2+ and ouabain pre-exposure, peak hyperpolarizations to ACh superfusion wer e somewhat decreased but not abolished. In addition, 4-5 mM increases of th e extracellular K+ concentration consistently depolarized:smooth muscle cel ls. These findings argue against the idea that smooth muscle inward rectifi er K+ channels and Na/K pumping play a role in the ACh-induced endothelium- dependent hyperpolarization of this preparation. Moreover, the slowing of s mooth muscle membrane hyperpolarization by Ba2+ is discussed in terms of th e influence of this ion on the release of hyperpolarizing factor.