Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output

Mutoh, Tatsushi; Bonham, Ann C.; Joad, Jesse P.

doi:10.1152/ajpregu.2000.279.4.r1215

Cited by 86 publications

(63 citation statements)

References 52 publications

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“…The specific neurokinin receptors mediating these responses are unknown. Previous studies have shown that all three neurokinin receptors are present and functional in regions of the nTS likely containing vagal afferent nerve terminals (32,33,35). We observed that systemic pretreatment with a combination of NK 1 and NK 3 receptor antagonists was equally effective at reducing the laryngeal capsaicin-induced reflex and blockade of all neurokinin receptor subtypes.…”

Section: Discussionmentioning

confidence: 47%

Synergistic interactions between airway afferent nerve subtypes mediating reflex bronchospasm in guinea pigs

Mazzone

Canning

2002

American Journal of Physiology-Regulatory, Integrative and Comp

108

117

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The hypothesis that airway afferent nerve subtypes act synergistically to initiate reflex bronchospasm in guinea pigs was addressed. Laryngeal mucosal application of capsaicin or bradykinin or the epithelial lipoxygenase metabolite 15( S)-hydroxyeicosatetraenoic acid evoked slowly developing but pronounced and sustained increases in tracheal cholinergic tone in situ. These reflexes were reversed by atropine and prevented by vagotomy, trimethaphan, or laryngeal denervation. Central nervous system-acting neurokinin receptor antagonists also abolished the reflexes without altering baseline cholinergic tone. Baseline tone was, however, reversed by disrupting pulmonary afferent innervation while preserving the innervation of the trachea and larynx. Surprisingly, selective pulmonary denervation also prevented the laryngeal capsaicin-induced tracheal reflexes, suggesting that laryngeal C-fibers act synergistically with continuously active intrapulmonary mechanoreceptors to initiate reflex bronchospasm. Indeed, reflex bronchospasm evoked by histamine was markedly potentiated by bradykinin, an effect mimicked by intracerebroventricular, but not intravenous, substance P. These data, as well as anatomic evidence for afferent nerve subtype convergence in the commissural nucleus of the solitary tract, suggest that airway nociceptors and mechanoreceptors may act synergistically to regulate airway tone.

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Section: Discussionmentioning

confidence: 47%

Synergistic interactions between airway afferent nerve subtypes mediating reflex bronchospasm in guinea pigs

Mazzone

Canning

2002

American Journal of Physiology-Regulatory, Integrative and Comp

108

117

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“…Thus we speculate that group B neurons may be inhibitory interneurons and could participate in the baroreflex depression reported after microinjection of higher doses of ANG II into this nTS region. In contrast, SP influences respiratory and gastric as well as cardiovascular function (10,24,66,72). Furthermore, the localization of our group B neurons responsive to ANG II and SP in the dorsal medial nTS region (77) is congruent with the distribution of vagal afferent projections from the esophagus and stomach (62,80).…”

Section: Perspectivesmentioning

confidence: 66%

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

Barnes

DeWeese

Andresen

2003

American Journal of Physiology-Regulatory, Integrative and Comp

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Barnes, Karen L., Dannette M. DeWeese, and Michael C. Andresen. Angiotensin potentiates excitatory sensory synaptic transmission to medial solitary tract nucleus neurons. Am J Physiol Regul Integr Comp Physiol 284: R1340-R1353, 2003. First published January 16, 2003 10.1152/ajpregu.00505.2002-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 nTS 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 . 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 receptors 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 al...

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“…The end-expiratory PCO 2 concentration was maintained at 3.0 -4.0% by adjusting the ventilation volume. Before and after the rat was paralyzed with gallamin triethiodide, we evaluated the adequacy of the depth of anesthesia by checking whether rapid variations of arterial BP (Ϯ5 mmHg) and heart rate (HR; Ϯ10%) would be caused by paw pinch every 0.5 h throughout the experimental procedure (18). If any one of these responses was found, urethane (0.1-0.2 g/kg) was supplemantally given with an IP injection.…”

Section: Methodsmentioning

confidence: 99%

Dose-dependent effects of l-carnosine on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats

Tanida¹,

Niijima²,

Fukuda³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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. Dose-dependent effects of L-carnosine on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats. Am J Physiol Regul Integr Comp Physiol 288: R447-R455, 2005. First published October 21, 2004; doi:10.1152/ajpregu.00275. 2004.-The physiological function of L-carnosine (␤-alanyl-L-histidine) synthesized in mammalian muscles has been unclear. Previously, we observed that intravenous (IV) injection of L-carnosine suppressed renal sympathetic nerve activity (RSNA) in urethaneanesthetized rats, and L-carnosine administered via the diet inhibited the elevation of blood pressure (BP) in deoxycorticosterone acetate salt hypertensive rats. To identify the mechanism, we examined effects of IV or intralateral cerebral ventricular (LCV) injection of various doses of L-carnosine on RSNA and BP in urethane-anesthetized rats. Lower doses (1 g IV; 0.01 g LCV) of L-carnosine significantly suppressed RSNA and BP, whereas higher doses (100 g IV; 10 g LCV) elevated RSNA and BP. Furthermore, we examined effects of antagonists of histaminergic (H1 and H3) receptors on L-carnosine-induced effects. When peripherally and centrally given, thioperamide, an H3 receptor antagonist, blocked RSNA and BP decreases induced by the lower doses of peripheral L-carnosine, whereas diphenhydramine, an H1 receptor antagonist, inhibited increases induced by the higher doses of peripheral L-carnosine. Moreover, bilateral lesions of the hypothalamic suprachiasmatic nucleus eliminated both effects on RSNA and BP induced by the lower (1 g) and higher (100 g) doses of peripheral L-carnosine. These findings suggest that low-dose L-carnosine suppresses and high-dose L-carnosine stimulates RSNA and BP, that the suprachiasmatic nucleus and histaminergic nerve are involved in the activities, and that L-carnosine acts in the brain and possibly other organs. suprachiasmatic nucleus; histaminergic nerve; autonomic nervous system; hypertension; hypotension L-CARNOSINE (␤-ALYNYL-L-HISTIDINE) is found in large amounts in skeletal muscles of vertebrates, where it is synthesized by carnosine synthetase (4). However, the physiological significance of L-carnosine has not been clear. A marked increase in the blood concentration of L-carnosine and hypotension was reported in a patient with a congenital deficiency of carnosinase, the L-carnosine-degrading enzyme (33). In addition, Lcarnosine concentrations in skeletal muscles of hypertensive rats were markedly reduced (13). These findings suggest that L-carnosine has hypotensive effects. We previously showed that intravenous (IV) injection of L-carnosine reduced the renal sympathetic nerve activity (RSNA) in urethane-anesthetized rats and that diets containing L-carnosine inhibited the hypertensive response in DOCA salt hypertensive rats (25).The RSNA, or the postganglionic sympathetic fibers that innervate the renal vascular bed (9), is controlled by the medullary sympathetic premotoneurons in the central nervous system (CNS) and plays an important role in modulating blood pressure (BP) (10, 29). We ...

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Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output

Cited by 86 publications

References 52 publications

Synergistic interactions between airway afferent nerve subtypes mediating reflex bronchospasm in guinea pigs

Synergistic interactions between airway afferent nerve subtypes mediating reflex bronchospasm in guinea pigs

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

Dose-dependent effects of l-carnosine on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats

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