Tissue perfusion is regulated so that the supply of blood, and in particular the supply of oxygen, can always match the demand of each organ or tissue. Regulation is conducted through the functioning of smooth muscle cells which spiral around the median layers of arteries and arterioles. For cerebral blood vasculature, the bed is innervated by sympathetic (noradrenaline producing) nerves to mediate constriction, and by parasympathetic (acetylcholine producing) nerves to mediate dilation. It is known that cyclic nucleotides also act in the regulation of tissue perfusion, and that cyclic GMP is a mediator of blood vessel relaxation induced by drugs such as nitroglycerine and by agents that function through the stimulation of release of EDRF (now known to be nitric oxide,NO). Thus NO is also a potent vasodilator. Additionally other regulators are involved in the control of perfusion of particular organs or tissues. For example there are a number of peptides present within the nerve fibre network which serves the cerebrovascular bed1 and which are thought to input into cerebral blood flow. All of these regulators are known to be under the direct control of blood pCO2 and blood pH, and so at first sight it might seem unnecessary for oxygen to directly and independently regulate arteriole dilation and contraction. However there are a number of situations where changes in blood pH and pCO2 are not matched by physiologically proportionate changes in blood pO2 (for example during a metabolic acidosis). Additionally, significant changes in pCO2 or pH can be systemic or partly so, suggesting that pH and pCO2 effects can spill from one organ to another. Problems could be expected to arise downstream under such a chain of command, which could have particularly undesirable effects where organs are perfused primarily or significantly by venous blood. It is also known that there are systems in the body which require a different (generally higher) blood pressure for optimum performance, for example the kidneys and lungs. Thus there is a need for input into the regulation of blood perfusion at the level of the individual organ or system.