Endothelial [Ca ²⁺] _i is an integrating signal for the vascular tone in rat aortae

Abstract

Background

Although various endothelium-dependent relaxing factors (endothelial autacoids) are released upon the elevation of endothelial cytosolic free Ca ²⁺ concentration (EC [Ca ²⁺] _i), the quantitative relationship between EC [Ca ²⁺] _i and vascular tone remains to be established. Moreover, whether the basal release of endothelial autacoids is modulated by basal EC [Ca ²⁺] _i is still unclear. We assessed these issues by using a novel method that allows simultaneous recording of EC [Ca ²⁺] _i and vascular displacement in dissected rat aortic segments.

Results

Receptor-dependent (acetylcholine) or independent (ionomycin) agonists caused immediate EC [Ca ²⁺] _i elevation followed by vasorelaxation in preparations pre-contracted with phenylephrine. Low doses of agonists induced small EC [Ca ²⁺] _i elevations (about 100 nmol/L) and concomitant half-maximal vasorelaxation. At high doses, agonists elevated EC [Ca ²⁺] _i to μmol/L range with little additional vasodilatation. When EC [Ca ²⁺] _i was plotted against the vasorelaxation, the curves were almost identical for both acetylcholine and ionomycin treatments, in the presence or absence of various endothelial autacoid inhibitors. Calcium-free solution reduced basal EC [Ca ²⁺] _i and induced a drastic vasoconstriction. Endothelial autacoid inhibitors reduced EC [Ca ²⁺] _i changes and abolished both agonist-induced vasodilatation and calcium-free solution-induced vessel contraction. When the EC [Ca ²⁺] _i was completely chelated by 40 μmol/L BAPTA, the acetylcholine-evoked vasorelaxation could be abolished as well. However, when the EC [Ca ²⁺] _i was partially chelated by 20 μmol/L BAPTA, the acetylcholine-evoked vasorelaxation was almost unaffected.

Conclusions

These results indicate that vascular tone is modulated by subtle changes of EC [Ca ²⁺] _i level, which seems to serve as an integrating signal in both basal and stimulated states.