Many experimental studies have shown that arterial smooth muscle cells respond with cytosolic calcium rises to vasoconstrictor stimulation. A low vasoconstrictor concentration gives rise to asynchronous spikes in the calcium concentration in a few cells (asynchronous flashing). With a greater vasoconstrictor concentration, the number of smooth muscle cells responding in this way increases (recruitment) and calcium oscillations may appear. These oscillations may eventually synchronize and generate arterial contraction and vasomotion. We show that these phenomena of recruitment and synchronization naturally emerge from a model of a population of smooth muscle cells coupled through their gap junctions. The effects of electrical, calcium, and inositol 1,4,5-trisphosphate coupling are studied. A weak calcium coupling is crucial to obtain a synchronization of calcium oscillations and the minimal required calcium permeability is deduced. Moreover, we note that an electrical coupling can generate oscillations, but also has a desynchronizing effect. Inositol 1,4,5-trisphosphate diffusion does not play an important role to achieve synchronization. Our model is validated by published in vitro experiments obtained on rat mesenteric arterial segments.

We tested for dye coupling between arteriolar smooth muscle cells (SMC) and endothelial cells (EC) and investigated the correspondence of vasomotor activity with changes in the membrane potential (Vm) of EC and SMC during blood flow control. Female golden hamsters (n = 8, 90-170 g) were anesthetized (pentobarbital sodium, 60 mg/kg ip). A cheek pouch was spread over an optical pedestal, transilluminated, and irrigated with physiological saline solution (37 degrees C, pH 7.4). Glass microelectrodes were filled with 3 M KCl or with Lucifer yellow dye (LY, mol wt 470; 106 mM). SMC or EC of arterioles (ID, 20-50 microns) containing blood flow were impaled under a stereomicroscope. Vm was similar [-48 +/- 3 and -52 +/- 4 mV (means +/- SE)] with KCl (n = 6) or LY (n = 13) microelectrodes, respectively. Acetylcholine (5 x 10(-6) M) increased Vm from -47 +/- 3 to -67 +/- 4 mV (n = 5; P less than 0.01) concomitant with vasodilation. Spontaneous slow waves in Vm (2/min, 15-30 mV) were observed in arterioles with vasomotion. In cells identified with LY microinjection, resting Vm was -52 +/- 8 and -44 +/- 2 mV for EC (n = 3) and SMC (n = 3), respectively. SMC injected with LY did not show evidence of dye transfer to other SMC or to EC. When an EC was injected, the dye spread to many contiguous EC but not to SMC.(ABSTRACT TRUNCATED AT 250 WORDS)

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Alonso F, Boittin FX, Bény JL, Haefliger JA. Loss of connexin40 is associated with decreased endothelium-dependent relaxations and eNOS levels in the mouse aorta. Am J Physiol Heart Circ Physiol 299: H1365-H1373, 2010. First published August 27, 2010; doi:10.1152/ajpheart.00029.2010.-Upon agonist stimulation, endothelial cells trigger smooth muscle relaxation through the release of relaxing factors such as nitric oxide (NO). Endothelial cells of mouse aorta are interconnected by gap junctions made of connexin40 (Cx40) and connexin37 (Cx37), allowing the exchange of signaling molecules to coordinate their activity. Wild-type (Cx40 ϩ/ϩ ) and hypertensive Cx40-deficient mice (Cx40 Ϫ/Ϫ ), which also exhibit a marked decrease of Cx37 in the endothelium, were used to investigate the link between the expression of endothelial connexins (Cx40 and Cx37) and endothelial nitric oxide synthase (eNOS) expression and function in the mouse aorta. With the use of isometric tension measurements in aortic rings precontracted with U-46619, a stable thromboxane A2 mimetic, we first demonstrate that ACh-and ATPinduced endothelium-dependent relaxations solely depend on NO release in both Cx40 ϩ/ϩ and Cx40 Ϫ/Ϫ mice, but are markedly weaker in Cx40 Ϫ/Ϫ mice. Consistently, both basal and ACh-or ATP-induced NO production were decreased in the aorta of Cx40 Ϫ/Ϫ mice. Altered relaxations and NO release from aorta of Cx40 Ϫ/Ϫ mice were associated with lower expression levels of eNOS in the aortic endothelium of Cx40 Ϫ/Ϫ mice. Using immunoprecipitation and in situ ligation assay, we further demonstrate that eNOS, Cx40, and Cx37 tightly interact with each other at intercellular junctions in the aortic endothelium of Cx40 ϩ/ϩ mice, suggesting that the absence of Cx40 in association with altered Cx37 levels in endothelial cells from Cx40 Ϫ/Ϫ mice participate to the decreased levels of eNOS. Altogether, our data suggest that the endothelial connexins may participate in the control of eNOS expression levels and function. connexin40; connexin37; endothelium-dependent relaxation; endothelial nitric oxide synthase

It is well-known that cyclic variations of the vascular diameter, a phenomenon called vasomotion, are induced by synchronous calcium oscillations of smooth muscle cells (SMCs). However, the role of the endothelium on vasomotion is unclear. Some experimental studies claim that the endothelium is necessary for synchronization and vasomotion, whereas others report rhythmic contractions in the absence of an intact endothelium. Moreover, endothelium-derived factors have been shown to abolish vasomotion by desynchronizing the calcium signals in SMCs. By modeling the calcium dynamics of a population of SMCs coupled to a population of endothelial cells, we analyze the effects of an SMC vasoconstrictor stimulation on endothelial cells and the feedback of endothelium-derived factors. Our results show that the endothelium essentially decreases the SMCs calcium level and may move the SMCs from a steady state to an oscillatory domain, and vice versa. In the oscillatory domain, a population of coupled SMCs exhibits synchronous calcium oscillations. Outside the oscillatory domain, the coupled SMCs present only irregular calcium flashings arising from noise modeling stochastic opening of channels. Our findings provide explanations for the published contradictory experimental observations.