Burn-induced alterations in cardiac beta-adrenergic receptors.

Abstract

Previous studies in our laboratory have demonstrated that burn injury (45% total body surface area, 3rd-degree scald burn) diminishes contractile and relaxation function in the isolated perfused guinea pig heart. The mechanisms responsible for the burn-mediated dysfunction are not well understood. Therefore the purpose of this study was to examine the inotropic response to isoproterenol, a beta-adrenergic agonist, and burn-induced alterations in beta-adrenergic receptors (beta-AR) in adult guinea pig hearts. Isoproterenol dose-response curves were generated in isolated perfused hearts from sham-burned and burned guinea pigs. In addition, binding studies were performed using [125I]iodocyanopindolol on hearts from sham-burned and burned guinea pigs. Both the functional response and sensitivity to isoproterenol were significantly diminished 24 h after burn injury. beta-AR density (binding capacity, Bmax) and affinity were determined by Scatchard analysis. Agonist competition curves were performed in the presence or absence of 0.1 mM 5'-guanylyl imidodiphosphate. There was no difference in Bmax in membranes from sham-burned and burned hearts; however, the affinity of beta-AR was significantly decreased after burn injury compared with sham burn [dissociation constant = 32.5 +/- 1.9 (mean +/- SE), n = 10, vs. 26.7 +/- 1.7 pM, n = 10, P = 0.039]. Furthermore, the fraction of receptors in a high-affinity state (those functionally coupled to Gs protein) was significantly decreased after burn injury compared with sham burn (41.2 +/- 4.7%, n = 9, vs. 54 +/- 2%, n = 9, P = 0.023).(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: T M Kaufman, J W Horton
• Journal: The American journal of physiology (Am J Physiol) Vol. 262 Issue 5 Pt 2 Pg. H1585-91 (May 1992) ISSN: 0002-9513 [Print] United States
• PMID: 1350425 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adrenergic beta-Agonists
• Catecholamines
• Receptors, Adrenergic, beta
• Guanylyl Imidodiphosphate
• Isoproterenol

Topics

• Adrenergic beta-Agonists (pharmacology)
• Animals
• Binding, Competitive
• Burns (blood, metabolism)
• Catecholamines (blood)
• Dose-Response Relationship, Drug
• Guanylyl Imidodiphosphate (pharmacology)
• Guinea Pigs
• Isoproterenol (pharmacology)
• Male
• Myocardium (metabolism)
• Receptors, Adrenergic, beta (metabolism)