Altered norepinephrine content and ventricular function in p75NTR-/- mice after myocardial infarction

Christina U. Lorentz, William R. Woodward, Kevin Tharp, Beth A. Habecker

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Cardiac sympathetic neurons stimulate heart rate and the force of contraction through release of norepinephrine. Nerve growth factor modulates sympathetic transmission through activation of TrkA and p75NTR. Nerve growth factor plays an important role in post-infarct sympathetic remodeling. We used mice lacking p75NTR to examine the effect of altered nerve growth factor signaling on sympathetic neuropeptide expression, cardiac norepinephrine, and ventricular function after myocardial infarction. Infarct size was similar in wildtype and p75NTR-/- mice after ischemia-reperfusion surgery. Likewise, mRNAs encoding vasoactive intestinal peptide, galanin, and pituitary adenylate cyclase activating peptides were identical in wildtype and p75NTR-/- cardiac sympathetic neurons, as was expression of the TrkA neurotrophin receptor. Norepinephrine content was elevated in the base of the p75NTR-/- ventricle compared to wildtype, but levels were identical below the site of occlusion. Left ventricular pressure, dP/dt MAX, and dP/dt MIN were measured under isoflurane anesthesia 3 and 7days after surgery. Ventricular pressure decreased significantly 3days after infarction, and deficits in dP/dt MAX were revealed by stimulating beta receptors with dobutamine and release of endogenous norepinephrine with tyramine. dP/dt MIN was not altered by genotype or surgical group. Few differences were observed between genotypes 3days after surgery, in contrast to low pressure and dP/dt MAX previously reported in control p75NTR-/- animals. Seven days after surgery ventricular pressure and dP/dt MAX were significantly lower in p75NTR-/- hearts compared to WT hearts. Thus, the lack of p75NTR did not enhance cardiac function after myocardial infarction.

Original languageEnglish (US)
Pages (from-to)13-19
Number of pages7
JournalAutonomic Neuroscience: Basic and Clinical
Volume164
Issue number1-2
DOIs
StatePublished - Oct 28 2011

Keywords

  • Cardiac ischemia-reperfusion
  • Nerve growth factor
  • Norepinephrine

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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