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1 Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA; Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, USA
2 Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA
3 Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, USA; Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA
4 Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA
5 Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA
* To whom correspondence should be addressed. E-mail: zjchen01{at}gwise.louisville.edu.
The nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DmnX) innervate distinct populations of cardiac ganglionic principal neurons. This anatomical evidence suggests that these two nuclei play different roles (6). However, lesion of the DmnX does not attenuate baroreflex sensitivity (4). The present study was to study the functional role of the NA in the baroreflex control of the heart rate. Domoic acid (DA) was injected into the left NA of Sprague-Dawley rats to lesion the NA. The neuronal loss was assessed using retrograde labeling and confocal microscopy. Heart rate (HR) changes induced by phenylephrine and sodium nitroprusside administration and following electrical stimulation of the left vagal trunk were measured at 15 days, and HR responses to left NA microinjection of L-glutamate were determined at 180 days post-lesion. Compared with vehicle control, DA lesions significantly reduced the population of NA motor neurons by 
68% (p <0.01) and attenuated baroreflex sensitivity by 83% (p<0.01) at 15 days. Similarly, electrical stimulation of the vagal trunks of DA lesioned animals led to attenuated decreases in HR responses. NA neuronal counts were reduced by 81% (p <0.01) and mean HR responses to L-glutamate injection into the lesioned NA were attenuated by 65% (p<0.01) at 180 days. Therefore, the NA plays a major role in baroreflex control of HR, and the integrity of the NA is critically important for the normal baroreflex control. In addition, NA lesions produce long-term anatomical and functional dysfunction of the nucleus, and thus, it may provide a useful tool for functional assessment of respective roles of the NA and DmnX.
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