Repeated sympathetic stimuli elicit the decline and disappearance of prostaglandin modulation and an increase of vascular resistance in humans.

To investigate the role of prostaglandins I2 and E2 in modulating the vasoconstrictor response to sympathetic stimulation, repeated and proximate cold pressor tests were performed in 23 healthy young volunteers. Limb vascular resistance (blood flow measured by venous occlusion plethysmography), prostaglandin I2 (as 6-ketoprostaglandin F1 alpha) and prostaglandin E2 plasma levels (detected by radioimmunoassay), and plasma catecholamines (detected by high-performance liquid chromatography and electrochemical detection) were measured. A progressive increase in the duration of the vasoconstrictor response was observed with repetition of cold applications (p less than 0.001, by analysis of variance for trends). This increase was associated with a progressive decrease in cold-induced elevation of 6-ketoprostaglandin F1 alpha and prostaglandin E2 plasma levels until, after five stimulations, neither prostaglandin was detectable. The maximum detected concentration of norepinephrine did not significantly change, but its area under the curve in time showed a trend toward an increase. Epinephrine levels did not significantly change. The increase of vascular resistance was significantly correlated with the decrease of both prostaglandins (r = 0.93, p less than 0.05 for prostaglandin E2 and r = 0.89, p less than 0.05 for 6-ketoprostaglandin F1 alpha), whereas no significant correlations were found between variations of vascular resistance and catecholamines. Prostaglandin blockade induced by diclofenac sodium administration caused, from the first cold application, a pattern of the vasoconstrictor response and plasma prostaglandin and norepinephrine changes similar to that observed at the fifth cold application in untreated subjects, when prostaglandins are no longer detectable in plasma. We conclude that an increased vasoconstrictor response to sympathetic stimulation in humans may result from a diminished inhibitory influence of prostaglandins on adrenergic transmission.