Angiotensin potentiates excitatory sensory synaptic transmission to medial solitary tract nucleus neurons

Karen L. Barnes, Dannette M. DeWeese, Michael C. Andresen
2003 American Journal of Physiology. Regulatory Integrative and Comparative Physiology  
Barnes, Karen L., Dannette M. DeWeese, and Michael C. Andresen. Angiotensin potentiates excitatory sensory synaptic transmission to medial solitary tract nucleus neurons. Femtomole doses of angiotensin (ANG) II microinjected into nucleus tractus solitarii (nTS) decrease blood pressure and heart rate, mimicking activation of the baroreflex, whereas higher doses depress this reflex. ANG II might generate cardioinhibitory responses by augmenting cardiovascular afferent synaptic transmission onto
more » ... S neurons. Intracellular recordings were obtained from 99 dorsal medial nTS region neurons in rat medulla horizontal slices to investigate whether ANG II modulated short-latency excitatory postsynaptic potentials (EPSPs) evoked by solitary tract (TS) stimulation. ANG II (200 fmol) increased TS-evoked EPSP amplitudes 20-200% with minimal membrane depolarization in 12 neurons excited by ANG II and glutamate, but not substance P (group A). Blockade of non-N-methyl-D-aspartate receptors eliminated TS-evoked EPSPs and responses to ANG II. ANG II did not alter TS-evoked EPSPs in 14 other neurons depolarized substantially by ANG II and substance P (group B). ANG II appeared to selectively augment presynaptic sensory transmission in one class of nTS neurons but had only postsynaptic effects on another group of cells. Thus ANG II is likely to modulate cardiovascular function by more than one nTS neuronal pathway. cardiovascular regulation; L-glutamate; substance P, non-Nmethyl-D-aspartate receptor THE NUCLEUS TRACTUS SOLITARII (nTS) in the dorsal medulla comprises rostrocaudally oriented columns of diverse neurons and fiber tracts that lie lateral to the walls of the fourth cerebral ventricle and join above the central canal caudal to the obex (4, 73). This complex structure, with bidirectional connections to medullary and forebrain nuclei that subserve autonomic functions, plays a major role in the regulation and integration of visceral systems, including normal and impaired cardiovascular mechanisms (60, 61, 82). Anatomic studies (25, 26, 43, 52, 85) and in vivo recordings (91) verify that a substantial proportion of the arterial baroreceptor sensory fibers that originate from recep-tors in the aortic arch and carotid sinus regions course through the solitary tract (TS) into the nTS and make their first synapse on neurons in the dorsal medial region of the nucleus. Neurons in this region also receive synaptic inputs from other viscera and brain autonomic nuclei via the TS (79). The nTS is a primary central site at which angiotensin (ANG) II influences cardiovascular function. Within the brain, the anatomic distributions of ANG II and its receptors and their mRNAs correlate reasonably well with the probable functions of the peptide (2, 57). However, the cellular mechanisms responsible for the cardiovascular effects of ANG II mediated by the nTS remain unclear. Microinjection of femtomole doses of ANG II into the dorsal medial region of the nTS produces a transient fall in blood pressure and heart rate very similar to the response to activation of the cardiovascular baroreflex in anesthetized rats (41, 71, 78) and evokes a comparable bradycardia in an in vitro beating heart-brain stem rat preparation (75). Paradoxically, however, higher doses evoke pressor responses, creating dose-response relationships that are biphasic. ANG II injection into the nTS also generates dose-dependent inhibition of baroreceptor reflex bradycardia in anesthetized and conscious rats (21, 64, 69) and attenuates baroreflex inhibition of cardiac sympathetic outflow in the rat heart-brain stem preparation (17, 75) . Because antagonists to the ANG II type 1 (AT 1 ) receptor injected into the nTS potentiate baroreceptor reflex responses, whereas ANG II type 2 receptor antagonists are ineffective (64, 65), endogenous ANG II may attenuate baroreflex function via AT 1 receptors in this region. Cardioinhibitory and neuronal actions of low-dose ANG II in the dorsal medial nTS region are also mediated by AT 1 receptors (16, 41, 53) . The neuronal pathways and mechanisms responsible for these contrasting actions of ANG II within the nTS have not been established. Several reports have documented that short-latency sensory synaptic transmission onto nTS neurons is mediated by non-N-methyl-D-aspartate (non-NMDA) ionotropic excitatory amino acid receptors (5, 46, 58, 83, 89, 90) , whereas longerlatency responses to synaptic activation of these cells
doi:10.1152/ajpregu.00505.2002 pmid:12531785 fatcat:pyjqcwqzxvambojzwctvriclxq