Does permanent carotid artery occlusion produce a 'preconditioning-like' effect towards more severe hypotension in energy metabolites? Role of cerebral adenosine.

1. The aim of the present study was to investigate the potential energy preserving effect of permanent bilateral common carotid artery occlusion (BCCAO) towards additional systemic hypotension of severe duration (30 min). In addition, the role of adenosine A1 receptors in cerebral ischaemic preconditioning was investigated in male Wistar rats. Thus, oligaemic rats were assigned randomly to continuous treatment with the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) or the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT), receiving daily intraperitoneal infusions of 0.1 mg/kg bodyweight CCPA or CPT or placebo (200 microL aqueous 2-hydropropyl-beta-cyclodextrin) at a delivery rate of 0.5 microL/h over 14 days. 2. Haemodynamic parameters and arterial blood gases were monitored. Rat cortical energy metabolites ATP, ADP, AMP, phosphocreatine and adenosine were measured using HPLC techniques. Adenosine A1 receptor expression was determined by immunhistochemistry and quantified by western blotting. 3. Two weeks of permanent BCCAO induced an 'energy saving' effect in rat cortical ATP concentrations. Under subchronic conditions, significant increases were detected in ADP and AMP concentrations after CCPA compared with placebo. Because similar changes were also seen after CPT, this adenosine A1 receptor-mediated effect does not seems to be specific. Furthermore, no differences in adenosine A1 receptor expression could be detected. 4. Adenosine was not specifically involved in the 'preconditioning-like' effect via the modulation of the adenosine A1 receptor in the present oligaemia model. Obviously, adenosine A1 receptor-specific effects after delayed cerebral ischaemic preconditioning do not seem to play an essential role if BCCAO is followed by a prolonged additional severe ischaemic event.