THE ROLE OF A(3) ADENOSINE RECEPTORS IN CENTRAL REGULATION OF ARTERIAL BLOOD-PRESSURE

1 Pharmacological studies have suggested that A(3) receptors are prese nt on central neurons. Recently this adenosine receptor subtype has be en identified in the rat and its presence in the central nervous syste m has been confirmed. 2 In this study we investigated the effects of a cute intracerebroventricular (i.c.v.) injections of N-6-2-(4-aminophen yl)-ethyladenosine (APNEA), a non-selective A(3) adenosine receptor ag onist, on arterial blood pressure (ABP) and heart rate (HR), after tre atment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective an tagonist of A(1) adenosine receptors. 3 Anaesthetized rats, after DPCP X (12 mu g(-1) kg i.c.v.), were treated with APNEA (0.4-4 mu g kg(-1) i.c.v.) resulting in a transitory and dose-dependent decrease in arter ial blood pressure without a change in heart rate. APNEA also induced hypotensive responses;after i.c.v, pretreatment with aminophylline, at a dose of 20 mu g kg(-1). In contrast, pretreatment 48 h before, with 4 mu g kg(-1) i.c.v. of pertussis toxin reduced the hypotensive effec t induced by APNEA. Administration of APNEA at a higher dose (20 mu g kg(-1) i.c.v.), after DPCPX, induced a decrease in ABP of -66+/-5.4 mm Hg and after 3 min a decrease in heart rate of -62+/-6.0 beats min(-1) . Transection of the spinal cord abolished this significant fall in AB P, but not the decrease of HR. 4 These results suggest that a populati on of A(3)-receptors is present in the CNS, whose activation induces a decrease in blood pressure with no change of heart rate.