Systemic adenosine increase during cold pressor test is dependent on sympathetic activation

1. Following local vasoconstriction-inducing stimuli, such as the cold pressor test (CPT), significant changes occur in haemodynamics, with a rise in arterial blood pressure and heart rate (HR) due to the activation of the sympathetic nervous system. Among the compensatory mechanisms to local ischaemia, the endogenous nucleoside adenosine (ADO) has been suggested to play a relevant role by contributing to sympathetic stimulation. The possibility was investigated that CPT-induced increases in plasma ADO levels were not only an expression of the increased production of ADO in the ischaemic area, but also a consequence of systemic sympathoexcitatory mechanisms, thus showing a bidirectional involvement of the mechanisms of ADO formation. 2. The CPT was performed in 15 volunteers and mean arterial blood pressure (MABP) and HR were evaluated, together with plasma levels of noradrenaline (NA) and ADO in the tested and contralateral arm. The 15 subjects were then divided into three groups of five that were treated with either 5 mg transdermal clonidine weekly, 100 mg atenolol daily or 600 mg aminophylline twice daily. After 1 week treatment, the same test was repeated in the respective groups. 3. The CPT induced a rise in MABP and HR and an increase in plasma levels of NA and ADO. Increases in ADO were more pronounced in the tested arm. Clonidine blunted the haemodynamic response and NA release, while increases in ADO increase were reduced to a greater extent in the contralateral arm rather than the tested arm. Atenolol only affected MABP and HR without any effect on NA and ADO levels. Theophylline did not show any effect on CPT-induced changes. 4. In conclusion, local vasoconstriction and ischaemia induced in one arm following CPT are associated with haemodynamic changes dependent on the activation of the sympathetic system. The observed increase in plasma levels of ADO seems to be, in part, a direct expression of local responses to ischaemia (pre-dominant in the tested arm), but also appears as the consequence of systemic sympathoexcitatory mechanisms. Such increases in ADO are not dependent on a beta 1-adrenoceptor-mediated mechanism. Finally, theophylline, at a therapeutic dose, has no effect on the response to CPT.