Elevated myocardial interstitial norepinephrine concentration contributes to the regulation of Na+,K+-ATPase in heart failure

Ling Ping Lai, Tai-Hwang Fan, Joseph M. Delehanty, Akito Yatani, Chang Seng Liang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Myocardial Na+,K+-ATPase is reduced in congestive heart failure. To study the regulation of Na+,K+-ATPase in congestive heart failure, we performed Western and Northern blot analyses of ventricular myocardium of dogs with pacing-induced congestive heart failure and chronic norepinephrine infusion, using isoform-specific antibodies and cDNA probes. Congestive heart failure and norepinephrine infusion caused similar increases in myocardial interstitial norepinephrine concentration and reductions of myocardial Na+,K+-ATPase α3-subunit protein, but differed in their effects on myocardial Na+,K+-ATPase α3-subunit gene expression. Chronic norepinephrine infusion produced no changes in the steady-state mRNA level for the α3-subunit of Na+,K+-ATPase, suggesting that the changes in Na+,K+-ATPase protein were induced via a post-transcriptional mechanism. In contrast, down-regulation of the Na+,K+-ATPase α3-subunit in the failing heart was accompanied by a decreased α3-subunit mRNA level, indicating the presence of a transcriptional event. The α3-subunit protein content and mRNA level were not affected by either norepinephrine infusion or rapid ventricular pacing. We conclude that, while elevated myocardiaI interstitial norepinephrine levels may contribute substantially to the down-regulation of the Na+,K+-ATPase α3-subunit in the failing myocardium, additional regulatory factors are responsible for the decreased myocardial α3-subunit mRNA expression in congestive heart failure.

Original languageEnglish (US)
Pages (from-to)235-241
Number of pages7
JournalEuropean Journal of Pharmacology
Volume309
Issue number3
DOIs
StatePublished - Aug 15 1996
Externally publishedYes

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Norepinephrine
Heart Failure
Messenger RNA
Protein Subunits
Myocardium
Down-Regulation
sodium-translocating ATPase
Northern Blotting
Protein Isoforms
Complementary DNA
Western Blotting
Dogs
Gene Expression
Antibodies

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Elevated myocardial interstitial norepinephrine concentration contributes to the regulation of Na+,K+-ATPase in heart failure. / Lai, Ling Ping; Fan, Tai-Hwang; Delehanty, Joseph M.; Yatani, Akito; Liang, Chang Seng.

In: European Journal of Pharmacology, Vol. 309, No. 3, 15.08.1996, p. 235-241.

Research output: Contribution to journalArticle

Lai, Ling Ping ; Fan, Tai-Hwang ; Delehanty, Joseph M. ; Yatani, Akito ; Liang, Chang Seng. / Elevated myocardial interstitial norepinephrine concentration contributes to the regulation of Na+,K+-ATPase in heart failure. In: European Journal of Pharmacology. 1996 ; Vol. 309, No. 3. pp. 235-241.
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