Bradykinin and postganglionic sympathetic transmission.

The effect of bradykinin on postganglionic sympathetic neuroeffector transmission was studied in superfused strips of rabbit pulmonary artery and in perfused rabbit hearts. 1. In pulmonary artery strips preincubated with 3H-noradrenaline, bradykinin (1–100 nM) diminished the overflow of total tritiated compounds evoked by transmural stimulation at 2 Hz and simultaneously reduced stimulation-evoked contractions. The inhibition was stronger, the less time was allowed to elapse between addition of bradykinin and stimulation. The effect of bradykinin was not changed by atropine, but was abolished by indometacin and 5,8,11,14-eicosatetraynoic acid. 2. Separation of individual 3H-compounds showed that bradykinin and prostaglandin E2 (PGE2) caused proportionate reduction of the stimulation-evoked overflow of total radioactive material, 3H-noradrenaline, 3H-3,4-dihydroxyphenylglycol, and 3H-normetanephrine. 3. Bradykinin (1–100 nM) greatly increased the outflow of PGE from the tissue. The outflow peaked in the 3-min period after addition of bradykinin and then declined rapidly. PGF2α and the metabolites 15-keto-PGF2α, 13,14-dihydro-15-keto-PGF2α and 13,14-dihydro-15-keto-PGE2 were not detected. 4. In the heart, bradykinin (100 nM) diminished the overflow of endogenous noradrenaline evoked by sympathetic nerve stimulation at 3 Hz. Similar results were obtained in hearts perfused with atropine-containing medium. Indometacin, on the other hand, abolished the effect of bradykinin. 5. Bradykinin (100 mM) greatly increased the venous outflow of PGE. PGE2α and the metabolites 15-keto-PGF2α, 13,14-dihydro-15-keto-PGF2α and 13,14-dihydro-15-keto-PGE2 were not detected. 6. It is concluded that bradykinin inhibits the nerve impulse-evoked release of noradrenaline, and consequently postganglionic sympathetic neuroeffector transmission, by enhancing the biosynthesis of prostaglandins of the E series; however, a contribution to the inhibition by other products of the fatty acid cyclooxygenase pathway cannot be ruled out. No prostaglandin-independent presynaptic effect of bradykinin was found.