Myocardial adrenergic responsiveness after lethal and nonlethal doses of endotoxin

R. E. Shepherd, C. H. Lang, K. H. McDonough

Research output: Contribution to journalArticle

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Abstract

A dose-dependent impairment of intrinsic myocardial performance has been observed following in vivo administration of endotoxin. The present study reports a dose-dependent increase in plasma catecholamines following endotoxin (ET) that may impair β-adrenergic responsiveness. Hearts were removed from pentobarbital-anesthetized rats 4 h after a bolus injection of saline or ET (1,000, 100, or 10 μg/100 g body wt) and were studied as isolated cell preparations following collagenase digestion. Responsiveness of isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in myocytes prepared from hearts of animals injected with 10 and 100 μg ET was decreased when compared with control rats and was significantly blunted in myocytes prepared from animals receiving 1,000 μg ET. Similar sensitivities of the cAMP system existed, as judged by similar half-maximum effective concentration values. cAMP accumulation in the presence of 1 μM forskolin was depressed in myocytes from the 1,000-μg ET animals; β-adrenergic receptor density was decreased 25% (P < 0.05) in myocytes from high-dose ET animals when compared with control animals. This was accompanied by a nonsignificant reduction in the affinity of binding sites for (±) [3H]CGP 12177. The blunted myocyte hormonal responsiveness following ET challenge appears to be related to the decreased activity of the adenylate cyclase that may be attributed to alterations in both receptor density and in the adenylate cyclase itself.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume252
Issue number2
StatePublished - Jan 1 1987

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Endotoxins
Adrenergic Agents
Muscle Cells
Adenylyl Cyclases
Collagenases
Colforsin
Pentobarbital
Isoproterenol
Cyclic AMP
Adrenergic Receptors
Catecholamines
Digestion
Binding Sites
Injections

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Myocardial adrenergic responsiveness after lethal and nonlethal doses of endotoxin",
abstract = "A dose-dependent impairment of intrinsic myocardial performance has been observed following in vivo administration of endotoxin. The present study reports a dose-dependent increase in plasma catecholamines following endotoxin (ET) that may impair β-adrenergic responsiveness. Hearts were removed from pentobarbital-anesthetized rats 4 h after a bolus injection of saline or ET (1,000, 100, or 10 μg/100 g body wt) and were studied as isolated cell preparations following collagenase digestion. Responsiveness of isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in myocytes prepared from hearts of animals injected with 10 and 100 μg ET was decreased when compared with control rats and was significantly blunted in myocytes prepared from animals receiving 1,000 μg ET. Similar sensitivities of the cAMP system existed, as judged by similar half-maximum effective concentration values. cAMP accumulation in the presence of 1 μM forskolin was depressed in myocytes from the 1,000-μg ET animals; β-adrenergic receptor density was decreased 25{\%} (P < 0.05) in myocytes from high-dose ET animals when compared with control animals. This was accompanied by a nonsignificant reduction in the affinity of binding sites for (±) [3H]CGP 12177. The blunted myocyte hormonal responsiveness following ET challenge appears to be related to the decreased activity of the adenylate cyclase that may be attributed to alterations in both receptor density and in the adenylate cyclase itself.",
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Myocardial adrenergic responsiveness after lethal and nonlethal doses of endotoxin. / Shepherd, R. E.; Lang, C. H.; McDonough, K. H.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 252, No. 2, 01.01.1987.

Research output: Contribution to journalArticle

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