Intercellular calcium dynamics in smooth muscle cells : propagation of arterial vasomotion and influence of the endothelium

Muscular arteries are able to actively modify their diameter by modulating the tone of the smooth muscle cells located within the arterial wall. A small variation of lumen diameter has a large influence on blood flow as well as on arterial pressure. The cardiovascular system pressure is mainly regulated by the resistance arteries and arterioles. Most of these arteries show cyclic variations of their diameter. This phenomenon is known as vasomotion and is in no way linked to any other physiological cycle like heartbeat or respiratory cycles. This phenomenon can be observed as well in vivo as in vitro. The arterial diameter oscillations are attributed to the contractile activity of the smooth muscle cells which is directly linked to their intracellular calcium concentration. Although observed since years, the mechanisms underlying vasomotion remain not well understood. It is known that arterial vasomotion is modified by apparition of abnormalities in the contractile mechanisms of arteries linked to cardiovascular diseases like hypertension. A better understanding of this phenomenon could therefore contribute to better treatments or diagnosis of such diseases. This thesis is divided in two parts which have each the goal to clear up a definite aspect of arterial vasomotion. The experiments have been performed in vitro on resistance arteries: the rat mesenteric arteries. These arteries have been observed under confocal fluorescence microscope allowing to quantify the intracellular calcium concentration in smooth muscle cells. In the first part of this work, we investigate the role played by the endothelium on arterial vasomotion. So far, contradictory results have been related in the literature about the role of the endothelium in the onset and maintenance of vasomotion. Even the elementary question of knowing if vasomotion can arise without an intact endothelium is quite controversial. To understand how the endothelium may either abolish or promote vasomotion, we have stimulated rat mesenteric arterial strips with a vasoconstrictor: the phenylephrine. Our results show that the endothelium is not necessary for vasomotion. However, when the endothelium is removed the phenylephrine concentration needed to induce vasomotion is lower and the rhythmic contractions occur for a narrower range of phenylephrine concentrations. By selectively inhibiting the endothelium-derived relaxing products, we demonstrate that these substances may either induce or abolish vasomotion. On the one hand, when the strip is tonically contracted in a non-oscillating state, an endothelium-derived relaxation may induce vasomotion. On the other hand, if the strip displays vasomotion, a relaxation may induce a transition to a non-oscillating state with a small contraction. In conclusion, our findings clarify the role of the endothelium on vasomotion and reconcile the seemingly contradictory observations reported in the literature. In the second part of this thesis we are interested i