Myocardial adrenergic responsiveness after lethal and nonlethal doses of endotoxin
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 ..beta..-adrenergic responsiveness. Hearts were removed from pentobarbital-anesthetized rats 4 h after a bolus injection of saline or ET 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 ..mu..g ET was decreased when compared with control rats and was significantly blunted in myocytes prepared from animals receiving 1000 ..mu..g ET. Similar sensitivities of the cAMP system existed, as judged by similar half-maximum effective concentration values. cAMP accumulation in the presence of 1 ..mu..M forskolin was depressed in myocytes from the 1000-..mu..g ET animals; ..beta..-adrenergic receptor density was decreased 25% 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 (+/-)(/sup 3/H)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.
- Research Organization:
- Louisiana State Univ. Medical Center, New Orleans
- OSTI ID:
- 5442288
- Journal Information:
- Am. J. Physiol.; (United States), Vol. 252:2
- Country of Publication:
- United States
- Language:
- English
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TOXINS
BIOLOGICAL EFFECTS
TRITIUM COMPOUNDS
UPTAKE
AMP
ANIMAL CELLS
BLOOD PRESSURE
CATECHOLAMINES
DOSE-RESPONSE RELATIONSHIPS
MYOCARDIUM
RATS
RECEPTORS
AMINES
ANIMALS
ANTIGENS
AROMATICS
BODY
CARDIOVASCULAR SYSTEM
HEART
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MUSCLES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
RODENTS
TOXIC MATERIALS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques