The role of myogenic relaxation, adenosine and prostaglandins in human forearm reactive hyperaemia.

Forearm blood flow was measured bilaterally in healthy young male and female volunteers, in the basal state and after upper-arm occlusion of arterial or venous blood flow for 1-20 min. The investigations were repeated after pre-treatment with drugs affecting vascular prostaglandins and/or adenosine. 2. Simultaneous arterial occlusion in one arm and venous occlusion in the contralateral arm for up to 20 min elicited a considerable reactive hyperaemia in the arm subjected to arterial occlusion, but completely failed to elevate the post-occlusive flow in the arm subjected to venous occlusion above the pre-occlusive level. 3. When the arterial occlusion was increased from 1 to 20 min there was a progressive increase in the subsequent reactive hyperaemia, up to 30 ml 100 ml tissue-1. The time dependence following 1-3 min of arterial occlusion was based on a facilitation of the peak post-occlusive flow, while prolongation of the arterial occlusion from 3 to 20 min augmented the reactive hyperaemia mainly by increasing its duration. 4. Inhibition of prostaglandin synthesis with ibuprofen reduced the total reactive hyperaemia following 3-5 min of arterial occlusion by up to 70%. This attenuation was due both to a reduction of peak post-occlusive flow and to a shortening of the duration of the post-occlusive hyperaemia. 5. The adenosine receptor antagonist theophylline reduced the reactive hyperaemia following 5 min of arterial occlusion by about 35%. Combined treatment with ibuprofen and theophylline did not reduce the reactive hyperaemia more than either drug alone. 6. Infusion of dipyridamole, a drug which inhibits the elimination of adenosine, reinforced the reactive hyperaemia by about 45%. This effect of dipyridamole was completely inhibited by administration of theophylline, and also by ibuprofen. 7. Plasma levels of adenosine, hypoxanthine and uric acid were maintained during the reactive hyperaemia, indicating increased production of purines during or immediately after the ischaemia. 8. It is concluded that the adequate stimulus for vascular relaxation in response to interruption of blood flow is omission of vessel wall distension. Local metabolic factors like endogenously formed prostaglandins and adenosine may act synergistically to this myogenic response but seem to be inactive alone. The lack of additive effects of ibuprofen and theophylline suggests a link between vascular relaxation induced by prostaglandins and by adenosine.