Attenuation of baroreflex sensitivity after domoic acid lesion of the nucleus ambiguus of rats

Abstract

The nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DmnX) innervate distinct populations of cardiac ganglionic principal neurons. This anatomic evidence suggests that these two nuclei play different roles (Cheng Z and Powley TL, Soc Neurosci Abstr 26: 1189, 2000). However, lesion of the DmnX does not attenuate baroreflex sensitivity (Cheng Z, Guo SZ, Lipton AJ, and Gozal D, J Neurosci 22: 3215–3226, 2002). The present study tested the functional role of the NA in baroreflex control of heart rate (HR). 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. HR changes induced by phenylephrine and sodium nitroprusside administration and after 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 postlesion. Compared with vehicle injections, 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 trunk 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 anatomic and functional dysfunction of the nucleus, and thus it may provide an useful model for functional assessment of respective roles of the NA and DmnX.