The regulation of blood flow and blood pressure depends on the coordinated behaviour of small arteries and arterioles. Under normal conditions blood vessels are in a state of partial constriction and changes in blood flow result from changes in the balance between stimuli which promote further constriction or those which promote relaxation and an increase in vessel diameter. A critical role for small arteries and arterioles is to match blood flow to metabolic demand so that active tissues are preferentially supplied with nutrients. This is especially important in the brain where reduction in the supply of nutrients during brief periods of time can lead to significant neural impairment and cognitive deficit. We have shown that in the systemic circulation, the cells which make up the blood vessel wall are electrically and chemically coupled through membrane channels called gap junctions and that coupling within and between the endothelial and smooth muscle layers is critical for the action of vasodilatory processes that enable the long range regulation of blood flow. We have also found that cell coupling in specialized cells of the small arterioles of the kidney is essential to the control of blood pressure and can actively regulate the renin-angiotensin system. In contrast, within the brain circulation, we have identified an important role for glial cells in the coordination of blood flow due to a surprising lack of appreciable intravascular coupling. Our studies in cerebral vessels have also demonstrated expression of novel variants of voltage dependent calcium channels which appear to contribute with more conventional calcium channels to the regulation of blood flow to the brain.