Faculty Collaboration Database

beta Adrenergic receptor desensitisation may serve a cardioprotective role. Cardiovasc Res 1992 Jun;26(6):608-14

Date

06/01/1992

Pubmed ID

1360332

DOI

10.1093/cvr/26.6.608

Scopus ID

2-s2.0-85047676086 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

OBJECTIVE: The aim was to test the hypothesis that beta adrenoceptor desensitisation is a form of cardioprotection whereby the myocardium is protected from the injurious effects of excessive adrenergic stimulation by isoprenaline.

METHODS: A new sensitive and specific method of identifying cardiac myocyte necrosis with monoclonal antimyosin was employed. Antibody labelled necrotic cardiomyocytes from male Sprague-Dawley rats (190-300 g) were identified by immunofluorescence. Homologous beta adrenoceptor desensitisation was induced by 9 d pretreatment with isoprenaline infusion (20 mg.kg-1.d-1), and heterologous desensitisation by treatment with 0.15% propylthiouracil in the diet for six weeks. The effects of isoprenaline induced cardiomyocyte injury in these animals were compared with those in control rats.

RESULTS: In euthyroid control rats, treatment with the beta adrenergic agonist, isoprenaline, produced prolonged tachycardia and hypotension, and a significant amount of cardiac myocyte necrosis subendocardially. When the same isoprenaline challenge was given to rats pretreated for 9 d with an isoprenaline infusion, the haemodynamic response was markedly attenuated and very little myocyte necrosis was noted. In the model of heterologous desensitisation occurring in hypothyroidism, isoprenaline challenge produced markedly diminished haemodynamic response and little cardiac myocyte necrosis.

CONCLUSIONS: In both homologous and heterologous models of beta adrenoceptor desensitisation, the susceptibility of the myocardium to isoprenaline induced cytotoxicity is markedly reduced.

Author List

Tan LB, Benjamin IJ, Clark WA

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic beta-Antagonists
Animals
Heart
Heart Diseases
Hypothyroidism
Infusion Pumps
Injections, Subcutaneous
Isoproterenol
Male
Myocardium
Necrosis
Rats
Rats, Sprague-Dawley
Time Factors