CONTINUOUS RELEASE OF VASODILATOR PROSTANOIDS CONTRIBUTES TO REGULATION OF RESTING FOREARM BLOOD-FLOW IN HUMANS

Continuous release of nitric oxide contributes to the maintenance of r esting tone in the human forearm and coronary circulations; however ev idence for a similar role of vasodilator prostanoids such as prostacyc lin is lacking. We examined whether continuous release of prostacyclin contributes to basal forearm blood flow. Flow was measured using veno us occlusion plethysmography in 38 healthy volunteers [mean age 21.3 /- 2.5 yr (+/-SD); 13 female, 25 male] at rest, after administration o f three incremental intra-arterial infusions of either the cyclooxygen ase inhibitor aspirin or placebo, and before and after administration of the endothelium-dependent and -independent dilators acetylcholine ( 30 mu g/min) and nitroprusside (1 mu g/min). To assess the effect of a spirin on the production of prostacyclin, plasma 6-keto prostaglandin F-1 alpha (6-keto-PGF(1 alpha); the stable metabolite of prostacyclin) was measured by simultaneous arterial and venous sampling. Aspirin pr oduced a time-and dose; dependent reduction in forearm blood flow, res ulting in a 32% decrease at the highest dose. The effect was maximal a fter 10 min. Flow at rest and after aspirin doses of 1, 3, and 10 mg/m in was 2.6 +/- 0.2, 2.3 +/- 0.2, 2.1 +/- 0.2, and 1.8 +/- 0.2 ml 100 m i forearm tissue(-1).min(-1), respectively (means +/- SE, P < 0.001). Commensurate with these data, the net forearm production of 6-keto-PGF (1 alpha), was 52.9 +/- 16.4, 11.7 +/- 8.6, 18.7 +/- 8.5, and 12.0 +/- 12.5 pg.100 mi forearm tissue(-1).min(-1) for the respective doses (P = 0.04). No time-dependent reduction in flow was seen in subjects wit h vehicle infusion. Aspirin did not affect the responses to acetylchol ine or nitroprusside. These data suggest that continuous release of pr ostacyclin plays a role in the maintenance of resting forearm blood fl ow There appears to be a direct link between the reduction in flow wit h aspirin and inhibition of prostacyclin production.