Activation of brain adenosine receptors evokes vasodilation in skin arterioles.

Metabolically stable adenosine (ADO) agonists were infused into cannulas chronically implanted in the lateral cerebral ventricle intracerebroventricularly (icv) while responses in skin microcirculation of pentobarbital-anesthetized hamsters were observed with intravital microscopy. Cyclohexyladenosine (CHA; A1-receptor selective; 0.0001-1 pmol) and N-ethylcarboxoamidoadenosine (NECA; A2-receptor selective; 0.01-0.05 pmol) were delivered in 10 microliters of bicarbonate-buffered Ringer vehicle. Mean systemic arterial blood pressure, heart rate, skin arteriolar diameter, and red blood cell velocity were continuously monitored. Blood flow was calculated from measurements of arteriolar diameter (20-40 microns) and red blood cell velocity. CHA icv caused dose-related decreases in blood pressure and heart rate, as well as increases in cutaneous perfusion. Comparable amounts of CHA administered intravenously evoked no response. Pretreatment with an A1-selective antagonist xanthine amine congener (XAC, 5 pmol icv or 1 mg/kg iv) had no effect on the depressor response but antagonized the bradycardia. In contrast, a nonselective antagonist 8-phenyltheophylline (8pTHEO, 5 pmol icv or 0.3 mg/kg iv) had no effect on the bradycardia but attenuated the depressor response. By either route, both antagonists prevented the cutaneous microcirculatory responses evoked by icv CHA. NECA icv produced hypotension but no change in the skin, and the depressor response was not altered by icv XAC. These observations provide direct evidence that chemical stimulation of central nervous system (CNS) ADO receptors is linked to a cutaneous vascular response that can be dissociated from other cardiorespiratory depressant actions of CNS ADO.