The crucial role of physiological Ca2+ concentrations in the production of endothelial nitric oxide and the control of vascular tone.

1. The effect of varying the extracellular Ca2+ concentration on the basal and acetylcholine (ACh)-induced release of nitric oxide (NO) from the rabbit aorta was investigated by use of a superfusion bioassay system. 2. Changes between 0.5 and 2.0 mM in the concentration of Ca2+ superfusing the detector bioassay tissues or perfusing endothelium-denuded donor aortae had no effect on the tone of these tissues. 3. Increasing the concentration of Ca2+ perfusing endothelium-containing donor aortae from zero to 1.25 mM caused a transient (24 +/- 9 min), concentration-dependent basal release of NO, which was attenuated at higher concentrations of Ca2+ (1.5-2.0 mM). 4. The duration of the effect of Ca2+ on the basal release of NO was increased by a concomitant infusion of L-arginine (100 microM) through the donor aorta. 5. Changes in the concentration of Ca2+ between 0.5 and 2.0 mM had a similar biphasic effect on the release of NO induced by ACh, which was also maximal at 1.25 mM Ca2+. 6. When Ca2+ was removed from the Krebs buffer perfusing the donor aorta, the basal release of NO declined within 2 min. In contrast, the release of NO induced by ACh declined progressively over 60 min. 7. Thus changes in the concentration of Ca2+ around the physiological range modulate the synthesis of NO by the vascular endothelium and consequently, vascular tone. This may account for the effects of dietary Ca2+ supplements on the control of some hypertensive states.