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Aequorin was used as an indicator of cytoplasmic Ca2+ levels during the action of vasodilators in potassium-depolarized strips of ferret portal vein. Moderate concentrations of isoprenaline produced either no change or an increase in cytoplasmic Ca2+ levels during smooth muscle relaxation. Only in the presence of very high concentrations of isoprenaline (greater than 10(-4) M) was a decrease in intracellular Ca2+ levels detectable. Both papaverine and forskolin also caused relaxations of the muscle while cytoplasmic Ca2+ levels were observed either not to change or to increase. When the muscles were relaxed either by decreasing the calcium concentration in the bathing medium or by the addition of sodium nitroprusside, light and force fell together. The ratio of force to light was greater when the muscle was relaxed with calcium depletion than with the addition of sodium nitroprusside, indicating that sodium nitroprusside was relaxing the muscle by more than just decreasing cytoplasmic Ca2+ levels. These results indicate that not all vasodilators cause a lowering of cytoplasmic Ca2+ levels and indicate that, in intact cells, agents associated with increases in cytoplasmic cyclic AMP levels can cause an uncoupling of calcium-force relations.

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