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

Abstract

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 μm) through the donor aorta. 5 Changes in the concentration of Ca^{2 +} 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.