KNOCKDOWN OF TYROSINE HYDROXYLASE IN THE NUCLEUS OF THE SOLITARY TRACT REDUCES ELEVATED BLOOD PRESSURE DURING CHRONIC INTERMITTENT HYPOXIA.

Bathina CS, Rajulapati A, Franzke M, Yamamoto K, Cunningham JT, Mifflin SW.
Am J Physiol Regul Integr Comp Physiol. 2013 Sep 18. [Epub ahead of print]. PMID: 24049117

Objective:   Sleep apnea produces chronic intermittent hypoxia (CIH) that causes elevations in sympathetic nerve activity and arterial pressure as a result of arterial chemoreceptor (CR) activation and subsequent activation of the NTS.  Since the CRs seem to preferentially activate the NTS A2 noradrenergic neurons, the role of these A2 neurons was examined by comparing the effect of CIH on wild type and tyrosine hydroxylase (TH) knockout rats.

Results:

·         Rats that had TH knocked down in the NTS with shRNA showed reduced change in MAP in the dark phase and a greater heart rate than controls.  Changes in heart rate persisted in normoxic phases in control rats, but not in knockdown rats.

·         In knockdown rats, there was a significant reduction in FosB immunoreactive cells in the PVN, but not in the controls.  This change did not significantly extend to the RVLM.

-DH