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

• Published in: European journal of pharmacology 1996-08, Vol.309 (3), p.235-241
• Main Authors: Lai, Ling-Ping, Fan, Tai-Hwang M., Delehanty, Joseph M., Yatani, Akito, Liang, Chang-seng
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Digitalis; Disease Models, Animal; Dogs; Heart; Heart failure; Heart Failure - metabolism; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Medical sciences; Myocardium - metabolism; Na +,K +-ATPase; Norepinephrine; Norepinephrine - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(96)00311-1

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 α 3-subunit protein, but differed in their effects on myocardial Na +,K +-ATPase α 3-subunit gene expression. Chronic norepinephrine infusion produced no changes in the steady-state mRNA level for the α 3-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 α 3-subunit in the failing heart was accompanied by a decreased α 3-subunit mRNA level, indicating the presence of a transcriptional event. The α 1-subunit protein content and mRNA level were not affected by either norepinephrine infusion or rapid ventricular pacing. We conclude that, while elevated myocardial interstitial norepinephrine levels may contribute substantially to the down-regulation of the Na +,K +-ATPase α 3-subunit in the failing myocardium, additional regulatory factors are responsible for the decreased myocardial α 3-subunit mRNA expression in congestive heart failure.