Isoproterenol inhibits transcription of cardiac cytokine genes induced by reactive oxygen intermediates

Walter H. Newman, Manuel R Castresana, Jerry G. Webb, Kristina Detmer, Zhongbiao Wang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Cytokines such as tumor necrosis factor α (TNF-α) are produced by the myocardium in heart disease and might be stimulated by reactive oxygen. In some cell types, cyclic adenosine monophosphate (AMP) inhibits TNF-α production. The authors tested the hypothesis that stimulation of cardiac β-adrenergic receptors would inhibit cytokine gene transcription induced by reactive oxygen. Methods: Rat hearts were perfused with buffer containing hypoxanthine. Reactive oxygen intermediates were generated by infusion of xanthine oxidase. Myocardial mRNA encoding 11 cytokines was determined. TNF-α, interleukin-6, and cyclic AMP were measured in the coronary effluent. Results: In control hearts, of the screened RNA, only mRNA encoding interleukin-1β, -4, and -6 was detected. Stimulation with hypoxanthine-xanthine oxidase (HX-XO) induced detectable mRNA for TNF-α and interleukin-5 and increased mRNA band density for interleukin-1β, -4, and -6. Simultaneous infusion of isoproterenol inhibited HX-XO-stimulated cytokine gene expression and caused release of cyclic AMP into the coronary effluent. In control hearts, TNF-α was not detected in the coronary effluent. After HX-XO administration, TNF-α was reliably detected at 60 min and interleukin-6 at 90 min. Simultaneous infusion of isoproterenol inhibited TNF-α and interleukin-6 release. Inclusion of propranolol in the perfusion buffer blocked the isoproterenol-induced inhibition of HX-XO-stimulated TNF-α release and release of cyclic AMP into the coronary effluent. In addition, elevating myocardial cyclic AMP with forskolin also blocked release of TNF-α stimulated by HX-XO. Finally, delaying infusion of isoproterenol until 30 min after HX-XO administration still suppressed release of TNF-α. Conclusions: Reactive oxygen species activate cytokine gene transcription in the myocardium. The sympathetic nervous system, acting through β-receptors to elevate myocardial cyclic AMP, regulates cardiac cytokine production by inhibition of transcription.

Original languageEnglish (US)
Pages (from-to)947-954
Number of pages8
JournalAnesthesiology
Volume96
Issue number4
DOIs
StatePublished - Apr 11 2002
Externally publishedYes

Fingerprint

Isoproterenol
Xanthine Oxidase
Tumor Necrosis Factor-alpha
Cytokines
Oxygen
Cyclic AMP
Genes
Interleukin-6
Messenger RNA
Interleukin-1
Interleukin-4
Myocardium
Buffers
Hypoxanthine
Sympathetic Nervous System
Interleukin-5
Colforsin
Propranolol
Adrenergic Receptors
Heart Diseases

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Isoproterenol inhibits transcription of cardiac cytokine genes induced by reactive oxygen intermediates. / Newman, Walter H.; Castresana, Manuel R; Webb, Jerry G.; Detmer, Kristina; Wang, Zhongbiao.

In: Anesthesiology, Vol. 96, No. 4, 11.04.2002, p. 947-954.

Research output: Contribution to journalArticle

Newman, Walter H. ; Castresana, Manuel R ; Webb, Jerry G. ; Detmer, Kristina ; Wang, Zhongbiao. / Isoproterenol inhibits transcription of cardiac cytokine genes induced by reactive oxygen intermediates. In: Anesthesiology. 2002 ; Vol. 96, No. 4. pp. 947-954.
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AU - Newman, Walter H.

AU - Castresana, Manuel R

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