Microinjection of L-glutamate into the intermediate nucleus tractus solitarii in anesthetized rats elicits hypotension, bradycardia, and apnea, simulating baroreceptor reflexes. Ablation of the nodose ganglion results in selective reduction of high-affinity uptake of L-glutanate in the nucleus tractus solitarii. L-Glutamate may be the neurotransmitter of afferent nerve fibers from arterial baroreceptors.

In the present study we investigated whether interruption of the chemoreceptor reflex by an electrolytic lesion of the commissural subnucleus of the nucleus tractus solitarii (commNTS) influenced pressor and bradycardic responses induced by microinjection of L-glutamate (L-Glu) into the medial NTS (mNTS) of conscious rats. Seven days after sham lesions, seven rats demonstrated significant pressor [change in mean arterial pressure (MAP) = +33 +/- 3 mmHg] and bradycardic [change in heart rate (HR) = -74 +/- 8 beats/min (bpm)] responses to chemoreceptor reflex activation by intravenous injection of KCN. Likewise, L-Glu (1 nmol in 100 nl) injected into the mNTS in sham rats induced pressor (+29 +/- 2 mmHg) and bradycardic responses (-90 +/- 8 bpm). However, in 11 rats with lesions in commNTS, pressor and bradycardic chemoreceptor reflex responses were abolished, and injection of L-Glu into the mNTS decreased MAP (-14 +/- 6 mmHg) and HR (-59 +/- 16 bpm) as is reported in anesthetized control rats. We conclude that pressor responses induced by L-Glu microinjected into the baroreceptor reflex region of mNTS in conscious rats depend on the integrity of the commNTS, which plays an important role in central chemoreceptor reflex pathways.

Numerous studies have suggested that nitric oxide (NO) in the nucleus tractus solitarii (NTS) participates in modulating cardiovascular function. Nitric oxide synthase (NOS), the enzyme responsible for synthesis of NO, exists in 3 isoforms: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). Although the distribution of nNOS in the NTS has been well documented, the distribution of eNOS in the NTS has not. Because recent studies have shown that eNOS may contribute to regulation of baroreceptor reflexes and arterial pressure, we examined the distribution of eNOS and the types of cells that express it in rat NTS by using multiple labels for immunofluorescent staining and confocal microscopy. Immunoreactivity (IR) for eNOS and nNOS was found in cells and processes in all NTS subnuclei, but eNOS-IR was more uniformly distributed than was nNOS-IR. Although structures containing either eNOS-IR or nNOS-IR were often present in close proximity, they never contained both isoforms. Almost all eNOS-IR positive structures, but no nNOS-IR positive structures, contained IR for the glial marker glial fibrillary acidic protein. Furthermore, while all nNOS-IR positive cells contained IR for the neuronal marker neuronal nuclear antigen (NeuN), none of the eNOS-IR positive cells contained NeuN-IR. We conclude that eNOS in the NTS is present only in astrocytes and endothelial cells, not in neurons. Our data complement previous physiological studies and suggest that although NO from nNOS may modulate neurotransmission directly in the NTS, NO from eNOS in the NTS may modulate cardiovascular function through an interaction between astrocytes and neurons.

The central nervous system has an important role in the second-to-second regulation of cardiac activity and vasomotor tone. Central lesions that lead to a disturbance in autonomic activity tend to cause electrocardiographic and pathological evidence of myocardial damage, cardiac arrhythmias, and disturbances of arterial blood pressure regulation. To a great extent such cardiovascular disturbances result from alterations in sympathetic activity. Similar alterations in sympathetic activity can occur under conditions of emotional stress and precipitate cardiac arrhythmias that can themselves lead to the syndrome of sudden death. Experimental and clinical evidence suggests that central neural mechanisms may be involved in this important human syndrome, but no central lesion has yet been identified to account for it. Recent experimental evidence, derived from hypertension research, suggests that chemical disturbances in the central nervous system, without accompanying structural lesions, may be found to explain cardiovascular disturbances such as sudden death and hypertension.

The cardiovascular effects of electrolytic lesions of the A2 group of catecholaminergic neurons of the dorsal medulla were analyzed in chronically instrumented rats. A2 lesions resulted after 24 hours, in an enduring increase in lability (variability) and augmented reactivity of the arterial pressure during spontaneous or elicited behaviors, without a change in the average arterial pressure. Heart rate and its variability were unchanged. A2 lesions almost abolished the bradycardia elicited by acutely elevating arterial pressure with phenylephrine, but not the hypotension elicited under anesthesia by carotid sinus stretch. Lability of arterial pressure could not be attributed to damage to cardiovagal neurons. Vagal blockade with atropine or methylatropine did not alter the mean or variability of the arterial pressure. Lability of arterial pressure was produced only by damage to A2 neurons and not by lesions in the area postrema or by transection of commissural fibers of the nucleus tractus solitarii (NTS). Moreover, the magnitude of lability was correlated directly with the amount of damage to A2. A2 lesions resulted in a reduction of dopamine-/3-hydroxylase activity to 60% of control in the NTS. We conclude that destruction of A2 neurons produces persistent lability and exaggerated reactivity of arterial pressure as a consequence of partial removal of the noradrenergic innervation of the NTS. The results suggest that noradrenergic neurons of A2 serve to modulate baroreceptor reflexes in NTS. The observation that lability of arterial pressure can occur in the absence of changes of average arterial pressure suggests distinctive anatomical networks subserving phasic and tonic control of the arterial pressure in the brainstem. Circ Res 46: [842][843][844][845][846][847][848][849][850][851][852][853] 1980