0168 : Endothelium dependent relaxation and T-type voltage-gated calcium channels

Abstract

T-type voltage-gated calcium channels (T-VGCC) are involved in the regulation of pulmonary arterial tone. Besides their roles in smooth muscle cell contraction, we investigate if T-VGCC could control vascular relaxation via endothelial calcium signaling regulation in mouse pulmonary arteries. Immunofluorescence labeling indicates that endothelial cells (as well as smooth muscle cells) express T-VGCC proteins (Cav3.1 and Cav3.2 isotypes). We show that nitric oxide (NO)-dependent relaxation induced by acetylcholine is reduced in the presence of T-VGCC antagonists (mibefradil, NNC 55- 0396) and in Cav3.1 knock-out mice. Acetylcholine induces an endothelial intracellular calcium increase which is reduced by the same types of inhibitors. By contrast, endothelium dependent relaxation induced by beta 2 adrenergic stimulation (with procaterol), which is calcium independent, is not inhibited by mibefradil or in Cav3.1 knock-out mice. Furthermore, in pathological condition (pulmonary hypertension induced by a chronic hypoxia), acetylcholine-mediated relaxation is reduced and even more in Cav3.1 knockout mice. In summary, in mice pulmonary arteries, acetylcholine and calciumdependent dilatation require T-VGCC. The present findings suggest that calcium influx through T-VGCC mediate a dual effect in pulmonary artery: a contraction when it occurred in smooth muscle cells and a dilatation when it occurred in endothelial cells.