Effect of different prostaglandin synthesis inhibitors on post-occlusive blood flow in human forearm

The vascular relaxation response in the human forearm that follows a short period of arterial occlusion (reactive hyperemia) was investigated with respect to its dependence on an intact PG synthesis. In 10 healthy subjects, five men and five women, forearm blood flow was measured, using venous occlusion plethysmography, in the basal state and during the recovery phase following 5 min of obstructed arterial flow. The subjects were studied at nine different occasions. At six of these they were pre-treated with the highest recommended doses of either of the PG synthesis inhibitors acetyl-salicylic acid, diclofenac, ibuprofen, indomethacin, naproxen or piroxicam; the remaining occasions were controls, performed in the absence of drugs in the beginning, middle, and end of the series. All the drugs significantly decreased the total reactive hyperemia following 5 min of arterial occlusion. Ibuprofen was the most efficient agent, inhibiting the total reactive hyperemia by more than 70%, and naproxen was least active, producing about 35% inhibition. The rest of the drugs diminished the total reactive hyperemia by 55-65%. Basal forearm blood flow was not affected by either of the agents. From these data we conclude that drugs which inhibit PG synthesis in man have in common the capacity to decrease post-occlusive reactive hyperemia. This indicates that an activation of the local release of arachidonic acid, leading to formation of vasodilator PG, is one of the main factors behind the vascular smooth muscle relaxation response to arterial occlusion.