Prostaglandin Mediated Inhibition of Noradrenaline Release at Different Nerve Impulse Frequencies

Abstract

Abstract The isolated perfused, sympathetically innervated rabbit heart was stimulated for 6 min at 2 or 10 Hz and the outflow of noradrenaline was monitored by assay of the perfusate from the organ during nerve stimulation. Continuous nerve stimulation caused a decline in the outflow of noradrenaline, which was more pronounced at the higher nerve stimulation frequency. When 5, 8, 11, 14‐eicosa tetranyoic acid, a compound known to inhibit prostaglandin synthesis in this preparation, was infused during nerve stimulation at 2 Hz, the relative outflow of noradrenaline was increased by about 90, while at 10 Hz no significant influence on the outflow of noradrenaline was observed. The outflow of endogenous prostaglandins was slightly more than doubled when the stimulation frequency was increased from 2 to 10 Hz. Simultaneously the sensitivity to exogenous prostaglandin E2 of the chronotropic response to nerve stimulation was decreased. The absence of endogenous inhibition of transmitter release at 10 Hz seems to be the result of both a decreased sensitivity of the noradrenaline release process to prostaglandins and an insufficient increase at this frequency in the amount of prostaglandin available to inhibit this process. The experiments show, that the prostaglandin mediated inhibition of the process of release of the sympathetic transmitter is more efficient at lower, more “physiological”, nerve impulse frequencies.