A dual function for adenosine 5'-triphosphate in the regulation of vascular tone. Excitatory cotransmitter with noradrenaline from perivascular nerves and locally released inhibitory intravascular agent.

Abstract

A dual function for adenosine 5'-triphosphate in the regulation of vascular tone is considered. Adenosine 5'-triphosphate can cause vasodilation, acting via P2-purinoceptors located on vascular endothelial cells to release an endothelium-derived relaxing factor which diffuses to the vascular smooth muscle and induces vasodilation. The main source of intraluminal adenosine 5'-triphosphate is likely to be endothelial cells, and its release can be measured during pathophysiological conditions such as ischemia and hypoxia, in amounts likely to be sufficient to activate endothelial P2-purinoceptors. Adenosine 5'-triphosphate can also be released during intravascular platelet aggregation and from intact and damaged vascular smooth muscle cells, and so may play a role in the complex physiological mechanisms controlling local vascular tone under normoxic conditions and during vessel injury. Evidence is also presented for adenosine 5'-triphosphate acting as an excitatory cotransmitter with noradrenaline from sympathetic perivascular nerves, to cause vasoconstriction via excitatory P2-purinoceptors located on vascular smooth muscle. The postjunctional mechanical and electrical responses of a number of blood vessels following perivascular nerve stimulation contain a component that is resistant to blockade of the alpha-adrenoceptor. This nonadrenergic response is mimicked by adenosine 5'-triphosphate and can be blocked by selective desensitization of the P2-purinoceptor by alpha,beta-methylene adenosine 5'-triphosphate. Vesicular storage of adenosine 5'-triphosphate and its release from sympathetic perivascular nerves has also been demonstrated. The functional significance of adenosine 5'-triphosphate acting intraluminally as a vasodilator and extraluminally as a vasoconstrictor neuronal agent in the control of vascular tone is discussed.