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

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.