Abstract-Vasomotion is the regular variation in tone of arteries. In our study, we suggest a model for the initiation of vasomotion. We suggest that intermittent release of Ca 2ϩ from the sarcoplasmic reticulum (SR, cytosolic oscillator), which is initially unsynchronized between the vascular smooth muscle cells, becomes synchronized to initiate vasomotion. The synchronization is achieved by an ion current over the cell membrane, which is activated by the oscillating Ca 2ϩ release. This current results in an oscillating membrane potential, which synchronizes the SR in the vessel wall and starts vasomotion. Therefore, the pacemaker of the vascular wall can be envisaged as a diffuse array of individual cytosolic oscillators that become entrained by a reciprocal interaction with the cell membrane. The model is supported by experimental data. Confocal [Ca 2ϩ ] i imaging and isometric force development in isolated rat resistance arteries showed that low norepinephrine concentrations induced SR-dependent unsynchronized waves of Ca 2ϩ in the vascular smooth muscle. In the presence of the endothelium, the waves converted to global synchronized oscillations of [Ca 2ϩ ] i after some time, and vasomotion appeared. Synchronization was also seen in the absence of endothelium if 8-bromo-cGMP was added to the bath. Using the patch-clamp technique and microelectrodes, we showed that Ca 2ϩ release can activate an inward current in isolated smooth muscle cells from the arteries and cause depolarization. These electrophysiological effects of Ca 2ϩ release were cGMP dependent, which is consistent with the possibility that they are important for the cGMP-dependent synchronization. Further support for the model is the observation that a short-lasting current pulse can initiate vasomotion in an unsynchronized artery as expected from the model.

That smooth muscles dilate and contract rhythmically has been known for a long time and the phenomenon has been studied for nearly as long. However, the causes and effects of smooth muscle oscillation (termed vasomotion) are far from clear. It is thought that vasomotion aids the delivery of oxygen to tissues surrounding capillary beds. On the other hand, unregulated vasomotion might participate in the development and maintenance of pathophysiological states. Nilsson and Aalkjaer review what is known about vasomotion and its consequences.

Endothelial cells in most vascular beds release a factor that hyperpolarizes the underlying smooth muscle, produces vasodilatation, and plays a fundamental role in the regulation of local blood flow and systemic blood pressure. The identity of this endotheliumderived hyperpolarizing factor (EDHF), which is neither NO nor prostacyclin, remains obscure. Herein, we demonstrate that in mesenteric resistance arteries, release of C-type natriuretic peptide (

1 Vasomotion is the oscillation of vascular tone with frequencies in the range from 1 to 20 min À1 seen in most vascular beds. The oscillation originates in the vessel wall and is seen both in vivo and in vitro.2 Recently, our ideas on the cellular mechanisms responsible for vasomotion have improved. Three different types of cellular oscillations have been suggested. One model has suggested that oscillatory release of Ca 2 þ from intracellular stores is important (the oscillation is based on a cytosolic oscillator). A second proposed mechanism is an oscillation originating in the sarcolemma (a membrane oscillator). A third mechanism is based on an oscillation of glycolysis (metabolic oscillator). For the two latter mechanisms, only limited experimental evidence is available. 3 To understand vasomotion, it is important to understand how the cells synchronize. For the cytosolic oscillators synchronization may occur via activation of Ca 2 þ -sensitive ion channels by oscillatory Ca 2 þ release. The ensuing membrane potential oscillation feeds back on the intracellular Ca 2 þ stores and causes synchronization of the Ca 2 þ release. While membrane oscillators in adjacent smooth muscle cells could be synchronized through the same mechanism that sets up the oscillation in the individual cells, a mechanism to synchronize the metabolic-based oscillators has not been suggested. 4 The interpretation of the experimental observations is supported by theoretical modelling of smooth muscle cells behaviour, and the new insight into the mechanisms of vasomotion has the potential to provide tools to investigate the physiological role of vasomotion.