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

S. M. Lanier, Kafait Malik

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24 Citations (Scopus)

Abstract

In the isolated rat heart prelabeled with [3H]norepinephrine ([3H]NE) and perfused with oxygenated Krebs-Ringer bicarbonate solution, we studied the effect of angiotensin II (AII) 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 meclofenamte) and also during infusion of PGE2 and PGI2. 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 AII (9 nM) into the heart did not alter the basal tritium overflow but increased that elicited by nerve stimulation. The AII-induced increase in the electrically evoked tritium 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. Moreover, 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(α) (the stable metabolite of PGI2), and this increase was abolished during infusion of either indomethacin (1.4 μM) or sodium meclofenamate (6.3 μM). The cyclooxygenase inhibitors enhanced the AII-induced increase in tritium overflow elicited by nerve stimulation, and this increment was minimized by infusion of either PGE2 or PGI2 (27-85 nM) into the heart. These data suggest that one or more products or 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.

Original languageEnglish (US)
Pages (from-to)594-601
Number of pages8
JournalCirculation research
Volume51
Issue number5
DOIs
StatePublished - Jan 1 1982

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Angiotensin II
Adrenergic Agents
Prostaglandins
Tritium
Epoprostenol
Dinoprostone
Cocaine
Indomethacin
Normetanephrine
Meclofenamic Acid
Adrenergic Fibers
Guanethidine
Prostaglandin Antagonists
Cyclooxygenase Inhibitors
Tetrodotoxin
Bicarbonates
Nerve Fibers
Arachidonic Acid
Electric Stimulation
Action Potentials

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Attenuation by prostaglandins of the facilitatory effect of angiotensin II at adrenergic prejunctional sites in the isolated Krebs-perfused rat heart",
abstract = "In the isolated rat heart prelabeled with [3H]norepinephrine ([3H]NE) and perfused with oxygenated Krebs-Ringer bicarbonate solution, we studied the effect of angiotensin II (AII) 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 meclofenamte) and also during infusion of PGE2 and PGI2. 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 AII (9 nM) into the heart did not alter the basal tritium overflow but increased that elicited by nerve stimulation. The AII-induced increase in the electrically evoked tritium 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. Moreover, 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(α) (the stable metabolite of PGI2), and this increase was abolished during infusion of either indomethacin (1.4 μM) or sodium meclofenamate (6.3 μM). The cyclooxygenase inhibitors enhanced the AII-induced increase in tritium overflow elicited by nerve stimulation, and this increment was minimized by infusion of either PGE2 or PGI2 (27-85 nM) into the heart. These data suggest that one or more products or 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.",
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N2 - In the isolated rat heart prelabeled with [3H]norepinephrine ([3H]NE) and perfused with oxygenated Krebs-Ringer bicarbonate solution, we studied the effect of angiotensin II (AII) 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 meclofenamte) and also during infusion of PGE2 and PGI2. 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 AII (9 nM) into the heart did not alter the basal tritium overflow but increased that elicited by nerve stimulation. The AII-induced increase in the electrically evoked tritium 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. Moreover, 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(α) (the stable metabolite of PGI2), and this increase was abolished during infusion of either indomethacin (1.4 μM) or sodium meclofenamate (6.3 μM). The cyclooxygenase inhibitors enhanced the AII-induced increase in tritium overflow elicited by nerve stimulation, and this increment was minimized by infusion of either PGE2 or PGI2 (27-85 nM) into the heart. These data suggest that one or more products or 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.

AB - In the isolated rat heart prelabeled with [3H]norepinephrine ([3H]NE) and perfused with oxygenated Krebs-Ringer bicarbonate solution, we studied the effect of angiotensin II (AII) 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 meclofenamte) and also during infusion of PGE2 and PGI2. 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 AII (9 nM) into the heart did not alter the basal tritium overflow but increased that elicited by nerve stimulation. The AII-induced increase in the electrically evoked tritium 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. Moreover, 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(α) (the stable metabolite of PGI2), and this increase was abolished during infusion of either indomethacin (1.4 μM) or sodium meclofenamate (6.3 μM). The cyclooxygenase inhibitors enhanced the AII-induced increase in tritium overflow elicited by nerve stimulation, and this increment was minimized by infusion of either PGE2 or PGI2 (27-85 nM) into the heart. These data suggest that one or more products or 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.

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