Infarction-induced cytokines cause local depletion of tyrosine hydroxylase in cardiac sympathetic nerves: Experimental Physiology-Research Paper

Diana C. Parrish, Eric N. Alston, Hermann Rohrer, Paul Nkadi, William Woodward, Günther Schütz, Beth Habecker

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Myocardial infarction causes a heterogeneity of noradrenergic transmission that contributes to the development of ventricular arrhythmias and sudden cardiac death. Ischaemia-induced alterations in sympathetic transmission include regional variations in cardiac noradrenaline (NA) and in tyrosine hydroxylase, the rate-limiting enzyme in NA synthesis. Inflammatory cytokines that act through gp130 are elevated in the heart after myocardial infarction. These cytokines decrease expression of tyrosine hydroxylase in sympathetic neurons, and indirect evidence suggests that they contribute to the local depletion of tyrosine hydroxylase in the damaged left ventricle. However, gp130 cytokines are also important for the survival of cardiac myocytes following damage to the heart. To examine the effect of cytokines on tyrosine hydroxylase and NA content in cardiac nerves we used gp130DBH-Cre/lox mice, which have a deletion of the gp130 receptor in neurons expressing dopamine β-hydroxylase. The absence of neuronal gp130 prevented the loss of tyrosine hydroxylase in cardiac sympathetic nerves innervating the left ventricle 1 week after ischaemia-reperfusion compared with wild-type C57BL/6J mice. Surprisingly, restoration of tyrosine hydroxylase in the damaged ventricle did not return neuronal NA content to normal levels. Noradrenaline uptake into cardiac nerves was significantly lower in gp130 knockout mice, contributing to the lack of neuronal NA stores. There were no significant differences in left ventricular peak systolic pressure, dP/dtmax or dP/dtmin between the two genotypes after myocardial infarction, but ganglionic blockade revealed differences in autonomic tone between the genotypes. Stimulation of the heart with dobutamine or release of endogenous NA with tyramine generated similar responses in both genotypes. Thus, the removal of gp130 from sympathetic neurons prevents the post-infarct depletion of tyrosine hydroxylase in the left ventricle, but does not alter NA content or cardiac function.

Original languageEnglish (US)
Pages (from-to)304-314
Number of pages11
JournalExperimental Physiology
Volume95
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Tyrosine 3-Monooxygenase
Infarction
Norepinephrine
Cytokines
Research
Heart Ventricles
Myocardial Infarction
Genotype
Ischemia
Neurons
Tyramine
Dobutamine
Dopaminergic Neurons
Sudden Cardiac Death
Mixed Function Oxygenases
Inbred C57BL Mouse
Cardiac Myocytes
Knockout Mice
Reperfusion
Cardiac Arrhythmias

ASJC Scopus subject areas

  • Physiology

Cite this

Infarction-induced cytokines cause local depletion of tyrosine hydroxylase in cardiac sympathetic nerves : Experimental Physiology-Research Paper. / Parrish, Diana C.; Alston, Eric N.; Rohrer, Hermann; Nkadi, Paul; Woodward, William; Schütz, Günther; Habecker, Beth.

In: Experimental Physiology, Vol. 95, No. 2, 02.2010, p. 304-314.

Research output: Contribution to journalArticle

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