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

Publisher Website
Google Scholar
Abstract
In the isolated rat heart prelabeled with [3H]norepinephrine ([3H]NE) and perfused with oxygenated Krebs-Ringer bicarbonate solution, the effect of angiotensin II (AII) on the overflow of 3H was studied before and during electrical stimulation of the cardiac sympathetic nerve plexus in the presence and absence of prostaglandin [PG] synthesis inhibitors (indomethacin, sodium meclofenamate) and also during infusion of PGE2 and PGI2. Stimulation of the cardiac nerve plexus increased the overflow of 3H; this overflow was most likely due to excitation of adrenergic nerve fibers, because it was blocked by tetrodotoxin or guanethidine or by removal of Ca from the perfusion medium. Infusion of AII (9 nM) into the heart did not alter the basal 3H overflow, but increased that elicited by nerve stimulation. The AII-induced increase in the electrically evoked 3H overflow consisted primarily of intact [3H]NE and was most likely due to enhanced transmitter release, because it was not reduced by inhibitors of neuronal (cocaine) and extraneuronal (normetanephrine) uptake. AII had no effect on the uptake of [3H]NE by the heart, whereas cocaine markedly reduced it. AII infusion into the heart increased the output of PGE2 and 6-keto PGF1.alpha. (the stable metabolite of PGI2), and this increase was abolished during infusion of either indomethacin (1.4 .mu.M) or sodium meclofenamate (6.3 .mu.M). The cyclooxygenase inhibitors enhanced the AII-induced increase in 3H overflow elicited by nerve stimulation and this increment was minimized by infusion of PGE2 or PGI2 (27-85 nM) into the heart. Apparently, one or more products of arachidonic acid, presumably PGI2 and/or PGE2, synthesized in the rat heart act to attenuate the effect of AII at prejunctional sites to enhance adrenergic transmitter release elicited by nerve impulses.

This publication has 18 references indexed in Scilit: