In humans, hypoxia leads to increased sympathetic neural outflow to skeletal muscle. However, blood flow increases in the forearm. The mechanism of hypoxia-induced vasodilation is unknown. To test whether hypoxia-induced vasodilation is cholinergically mediated or is due to local release of adenosine, normal subjects were studied before and during acute hypoxia (inspired O(2) 10.5%; approximately 20 min). In experiment I, aminophylline (50-200 microg. min(-1). 100 ml forearm tissue(-1)) was infused into the brachial artery to block adenosine receptors (n = 9). In experiment II, cholinergic vasodilation was blocked by atropine (0.4 mg over 4 min) infused into the brachial artery (n = 8). The responses of forearm blood flow (plethysmography) and forearm vascular resistance to hypoxia in the infused and opposite (control) forearms were compared. During hypoxia (arterial O(2) saturation 77 +/- 2%), minute ventilation and heart rate increased while arterial pressure remained unchanged; forearm blood flow rose by 35 +/- 6% in the control forearm but only by 5 +/- 8% in the aminophylline-treated forearm (P < 0.02). Accordingly, forearm vascular resistance decreased by 29 +/- 5% in the control forearm but only by 9 +/- 6% in the aminophylline-treated forearm (P < 0.02). Atropine did not attenuate forearm vasodilation during hypoxia. These data suggest that adenosine contributes to hypoxia-induced vasodilation, whereas cholinergic vasodilation does not play a role.

1 The cardioprotective e ect of N-[(1S, trans)-2-hydroxycyclopentyl]adenosine (GR79236), an adenosine A 1 receptor agonist, was compared with that produced by ischaemic preconditioning in an anaesthetized rabbit model of myocardial ischaemia and reperfusion. In addition, we examined the e ect of di erent body core temperatures on GR79236-or ischaemic preconditioning-induced cardioprotection when administered prior to ischaemia, and on cardioprotection induced by GR79236 administered 10 min prior to the onset of reperfusion. 2 When rabbits were subjected to 30 min occlusion of the left coronary artery, followed by 2 h reperfusion, GR79236 (3610 78 mol kg 71 i.v. (10.5 mg kg 71 i.v.)) or ischaemic preconditioning (5 min ischaemia followed by 5 min reperfusion), administered or applied 10 min prior to the occlusion, signi®cantly limited the development of infarction. The cardioprotective e ect of ischaemic preconditioning was signi®cantly greater than that seen after administration of GR79236. Pre-treatment with the selective adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 3.3610 76 mol kg 71 (1 mg kg 71 i.v.)), prevented the cardioprotective e ect of GR79236, but not that of ischaemic preconditioning. 3 Maintaining body core temperature at 38.58C rather than at 37.08C did not in¯uence infarct size in control groups of rabbits, but reduced the cardioprotective e ect of GR79236 when administered 10 min prior to occlusion or 10 min prior to the onset of reperfusion. The cardioprotective e ect of ischaemic preconditioning was not temperature-dependent. 4 In conclusion, myocardial protection conferred by GR79236 in anaesthetized rabbits is mediated via adenosine A 1 receptors. Myocardial protection can be conferred when GR79236 is administered before the onset of ischaemia or reperfusion, and is reduced when body core temperature is maintained at 38.58C rather than at 37.08C. In contrast, myocardial protection conferred by ischaemic preconditioning is not reduced by adenosine A 1 receptor blockade, or by maintaining body core temperature at 38.58C rather than at 37.08C. These ®ndings point to distinct di erences in the mechanisms of induction of myocardial protection by adenosine A 1 receptor agonist and ischaemic preconditioning. They also highlight the need for careful control of body core temperature when investigating the phenomenon of cardioprotection.