Attenuation by prostaglandins of the facilitatory effect of angiotensin II at adrenergic prejunctional sites in the isolated Krebs-perfused rat heart.

In the isolated rat heart prelabeled with [ 3 H]norepinephrine ([ 3 H]NE) and perfused with oxygenated Krebs-Ringer bicarbonate solution, we studied the effect of angiotensin II (All) on the overflow of tritium before and during electrical stimulation of the cardiac sympathetic nerve plexus in the presence and absence of prostaglandin synthesis inhibitors (indomethacin, sodium meclofenamate) and also during infusion of PGE2 and PGI 2 .Stimulation of the cardiac nerve plexus increased the overflow of tritium, which was most likely due to excitation of adrenergic nerve fibers because it was blocked by tetrodotoxin, guanethidine, or by removal of calcium from the perfusion medium.Infusion of All (9 nM) into the heart did not alter the basal tritium overflow but increased that elicited by nerve stimulation.The All-induced increase in the electrically evoked tritium overflow consisted primarily of intact [ 3 H]NE and was most likely due to enhanced transmitter release because it was not reduced by inhibitors of neuronal (cocaine) and extraneuronal (normetanephrine) uptake.Moreover, All had no effect on the uptake of [ 3 H]NE by the heart, whereas cocaine markedly reduced it.All infusion into the heart increased the output of PGE2 and 6-keto PGFi n (the stable metabolite of PGI2), and this increase was abolished during infusion of either indomethacin (1.4 /XM) or sodium meclofenamate (6.3 JIM).The cyclooxygenase inhibitors enhanced the All-induced increase in tritium overflow elicited by nerve stimulation, and this increment was minimized by infusion of either PGE2 or PGI 2 (27-85 nM) into the heart.These data suggest that one or more products of arachidonic acid, presumably PGI2 and/or PGE2, synthesized in the rat heart act to attenuate the effect of All at prejunctional sites to enhance adrenergic transmitter release elicited by nerve impulses.