Cardiovascular responses to microinjection of ANF into dorsal medulla of rats

1988 ◽  
Vol 255 (1) ◽  
pp. R182-R187 ◽  
Author(s):  
D. J. McKitrick ◽  
F. R. Calaresu

Atrial natriuretic factor (ANF) has been suggested as a putative neurotransmitter in central pathways involved in the control of the cardiovascular system. To investigate this possibility, 50 nl of 10(-7) M ANF were microinjected into discrete sites in the nucleus of the tractus solitarius (NTS) where baro- and chemoreceptor afferents terminate. Injections into 36 of a total of 66 sites in the NTS of paralyzed artificially ventilated Wistar rats under urethan anesthesia were found to produce a significant decline in heart rate [HR; -9.2 +/- 2.9 (SE) beats/min, P less than 0.05] and mean arterial pressure [MAP; -11.1 +/- 1.2 (SE) mmHg, P less than 0.01]. Similar responses were also present in anesthetized animals breathing spontaneously. Microinjection of an inactive peptide analogue or of saline did not produce cardiovascular changes. It was also found that ANF injection into the cuneate nucleus (20 of 38 sites) and the spinal trigeminal complex (28 of 42 sites) produced a decrease in MAP and HR that were of the same magnitude as those seen in the NTS. Injections of ANF into the medial longitudinal fasciculus (n = 22), hypoglossal nucleus (n = 9), area postrema (n = 16), and dorsal motor nucleus of the vagus (n = 11) did not change HR or MAP. These results suggest that ANF may serve as a neurotransmitter involved in cardiovascular reflexes mediated by specific nuclei in the dorsal medulla.

2005 ◽  
Vol 98 (4) ◽  
pp. 1442-1457 ◽  
Author(s):  
Qiuli Liu ◽  
Margaret T. T. Wong-Riley

Previously, we reported that the expression of cytochrome oxidase in a number of brain stem nuclei exhibited a plateau or reduction at postnatal day (P) 3–4 and a dramatic decrease at P12, against a general increase with age. The present study examined the expression of glutamate, N-methyl-d-aspartate receptor subunit 1 (NMDAR1), GABA, GABAB receptors, glycine receptors, and glutamate receptor subunit 2 (GluR2) in the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, medial accessory olivary nucleus, dorsal motor nucleus of the vagus, and cuneate nucleus, from P2 to P21 in rats. Results showed that 1) the expression of glutamate increased with age in a majority of the nuclei, whereas that of NMDAR1 showed heterogeneity among the nuclei; 2) GABA and GABAB expressions decreased with age, whereas that of glycine receptors increased with age; 3) GluR2 showed two peaks, at P3–4 and P12; and 4) glutamate and NMDAR1 showed a significant reduction, whereas GABA, GABAB receptors, glycine receptors, and GluR2 exhibited a concomitant increase at P12. These features were present but less pronounced in hypoglossal nucleus and dorsal motor nucleus of the vagus and were absent in the cuneate nucleus. These data suggest that brain stem nuclei, directly or indirectly related to respiratory control, share a common developmental trend with the pre-Bötzinger complex in having a transient period of imbalance between inhibitory and excitatory drives at P12. During this critical period, the respiratory system may be more vulnerable to excessive exogenous stressors.


2001 ◽  
Vol 29 (02) ◽  
pp. 211-220 ◽  
Author(s):  
Chang Hyun Lee ◽  
Han Sol Jung ◽  
Tae Young Lee ◽  
Sang Ryoung Lee ◽  
Sang Won Yuk ◽  
...  

The purpose of this morphological study was to investigate the relation between the meridian, meridian points and viscera using neuroanatomical tracers. The common locations of the spinal cord and brain projecting to the stomach and Zusanli were observed following injection of CTB (cholera toxin B subunit) and pseudorabies viruses (PRV-Ba, Bartha strain and PRV-Ba-Gal, galactosidase insertion) into the stomach and Zusanli (ST36). After 4–5 days of survival following injection into twelve rats, they were perfused, and their spinal cords and brains were frozen sectioned (30 μm). These sections were stained by X-gal histochemical, CTB and PRV-Bia immunohistochemical staining methods, and examined with the light microscope. The results were as follows: Commonly labeled medulla oblongata regions were dorsal motor nucleus of vagus nerve (DMV), nucleus tractus solitarius (NTS) and area postrema (AP) following injection of CTB and PRV-Ba-Gal into stomach and Zusanli, respectively. In the spinal cord, commonly labeled neurons were found in thoracic, lumbar and sacral spinal segments. Densely labeled areas were found in lamina IV, V, VII (intermediolateral nucleus) and X of the spinal cord. In the brain, commonly labeled neurons were found in the A1 noradrenalin cells/C1 adrenalin cells/caudoventrolateral reticular nucleus, dorsal motor nucleus of vagus nerve, nucleus tractus solitarius, area postrema, raphe obscurus nucleus, raphe pallidus nucleus, raphe magnus nucleus, gigantocellular nucleus, locus coeruleus, parabrachial nucleus, Kolliker-Fuse nucleus, A5 cell group, central gray matter, paraventricular hypothalamic nucleus, lateral hypothalamic nucleus, retrochiasmatic hypothalamic nucleus, bed nucleus of stria terminals and amygdaloid nucleus. Thus central autonomic center project both to the stomach and Zusanli. These morphological results suggest that there is a commonality of CNS cell groups in brain controlling stomach (viscera) and Zusanli (limb).


1995 ◽  
Vol 269 (6) ◽  
pp. R1301-R1307
Author(s):  
K. Kato ◽  
H. Yang ◽  
Y. Tache

Mechanisms involved in central thyrotropin-releasing hormone (TRH) analogue RX-77368-induced prevention of gastric lesions were investigated in urethan-anesthetized rats. Gastric lesions were induced by intragastric administration of ethanol (4 ml/kg) and assessed 1 h later by macroscopic visualization using computerized image analysis. RX-77368 (3, 5, and 10 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) decreased ethanol-induced gastric lesions by 79, 68, and 61%, respectively. RX-77368 at 1.5, 15, or 30 ng into the DMN or at 3 or 10 ng into the nucleus of the solitary tract, hypoglossal nucleus, or reticular field was ineffective in preventing mucosal damage. The protective effect of RX-77368 (3 ng into the DMN) was partly inhibited by peripheral injection of indomethacin and completely blocked by atropine, the calcitonin gene-related peptide antagonist, CGRP-(8-37), and NG-nitro-L-arginine methyl ester (L-NAME). L-arginine, but not D-arginine, reversed the effect of L-NAME. RX-77368 (3 ng into the DMN) enhanced gastric prostaglandin E2 (PGE2) release. These data indicate that low doses of TRH analogue act in the DMN to induce gastric protection against ethanol injury through muscarinic-, PGE2-, CGRP-, and nitric oxide-dependent mechanisms.


1989 ◽  
Vol 257 (1) ◽  
pp. H324-H329 ◽  
Author(s):  
M. J. Campagnole-Santos ◽  
D. I. Diz ◽  
R. A. Santos ◽  
M. C. Khosla ◽  
K. B. Brosnihan ◽  
...  

The amino terminal angiotensin heptapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro [ANG-(1–7)], is the major product formed during incubation of 125I-labeled ANG I or 125I-labeled ANG II with homogenates obtained from canine dorsomedial medulla oblongata. To determine whether ANG-(1–7) has central-mediated cardiovascular effects, this heptapeptide was microinjected into the dorsal medulla of chloralose-urethan-anesthetized rats. Unilateral injections of ANG-(1-7) into the medial nucleus tractus solitarii caused depressor and bradycardic effects at doses between 0.1 and 12.5 ng. Similar hypotensive responses accompanied with bradycardia were produced by injections of ANG-(1–7) into the dorsal motor nucleus of the vagus. In both nuclei, the monophasic depressor responses elicited by ANG-(1–7) were qualitatively similar to those found with injections of ANG II. Biphasic depressor-pressor responses of variable magnitude were produced by the injection of either angiotensin peptide at a high dose (250 ng). Because ANG-(1–7) has no direct vascular or dipsogenic effects, our findings suggest important differences in the receptor requirements for vascular and neural tissue of the dorsal medulla. Moreover, the data support the concept of tissue specific formation and action of angiotensin peptides in the brain.


2003 ◽  
Vol 285 (3) ◽  
pp. G566-G576 ◽  
Author(s):  
Marja D. Van Sickle ◽  
Lorraine D. Oland ◽  
Ken Mackie ◽  
Joseph S. Davison ◽  
Keith A. Sharkey

The aim of this study was to investigate the efficacy, receptor specificity, and site of action of Δ9-tetrahydrocannabinol (THC) as an antiemetic in the ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of cisplatin. The ED50 for retching was ∼0.1 mg/kg and for vomiting was 0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5 mg/kg ip) was ineffective. THC applied to the surface of the brain stem was sufficient to inhibit emesis induced by intragastric hypertonic saline. The site of action of THC in the brain stem was further assessed using Fos immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the solitary tract (NTS), but not other subnuclei of the NTS, was significantly reduced by THC rostral to obex. At the level of the obex, THC reduced Fos expression in the area postrema and the dorsal subnucleus of the NTS. The highest density of CB1 receptor immunoreactivity was found in the DMNX and the medial subnucleus of the NTS. Lower densities were observed in the area postrema and dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of staining in the commissural subnucleus of the NTS. These results show that THC selectively acts at CB1 receptors to reduce neuronal activation in response to emetic stimuli in specific regions of the dorsal vagal complex.


1999 ◽  
Vol 277 (4) ◽  
pp. R1104-R1111 ◽  
Author(s):  
Huiyuan Zheng ◽  
Lisa Kelly ◽  
Laurel M. Patterson ◽  
Hans-Rudolf Berthoud

To test the possible role of N-methyl-d-aspartate (NMDA) glutamate receptors in the transmission of gastrointestinal satiety signals at the level of the nucleus of the solitary tract (NTS), we assessed the effect of fourth ventricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on short-term sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not affecting initial rate of intake, significantly increased sucrose intake during the later phase of the meal (10–30 min, 8.9 ± 1.0 vs. 2.9 ± 0.8 ml, P < 0.01). In the medial subnucleus of the NTS, the area postrema, and the dorsal motor nucleus, MK-801 did not reduce gastric distension-induced Fos expression and itself did not significantly induce Fos expression. In the dorsomedial, commissural, and gelatinosus subnuclei, MK-801 in itself produced significant Fos expression and significantly reduced (−75%, P < 0.05) the ability of gastric distension to induce Fos expression, assuming an additive model with two separate populations of neurons activated by distension and the blocker. Although these results are consistent with NMDA receptor-mediated glutamatergic transmission of vagal satiety signals in general, they lend limited support for such a role in the transmission of specific gastric distension signals.


1995 ◽  
Vol 268 (1) ◽  
pp. R223-R230 ◽  
Author(s):  
K. A. Fraser ◽  
E. Raizada ◽  
J. S. Davison

We recently demonstrated that a meal induces c-fos immunoreactivity in the dorsal motor nucleus of the vagus (DMV), the nucleus of the tractus solitarius (NTS), and the area postrema (AP) of the rat brain stem. This response was not eliminated by the cholecystokinin A (CCK-A) antagonist L-364,718, a finding suggesting that feeding induces c-fos immunoreactivity by a pathway that is largely independent of CCK-A receptor activation. Consequently, the role of alternative gastrointestinal cues in the induction of c-fos was investigated. The induction of c-fos after oral-pharyngeal and esophageal stimuli was examined by use of a sham-feeding procedure via a gastric fistula. Gastric fistula-closed and fed rats displayed c-fos immunoreactivity similar to that of meal-fed rats seen previously. Fistula-open and fed rats showed the same degree of staining in the more rostral section of NTS examined as fistula-closed and fed rats, but fewer c-fos-positive nuclei in the more caudal level of the NTS. The potential for gastric distension to induce c-fos was assessed after the inflation of a gastric balloon. Physiological inflation of the balloon produced marked c-fos induction primarily in the medial NTS.


2006 ◽  
Vol 290 (6) ◽  
pp. G1350-G1358 ◽  
Author(s):  
Ying Li ◽  
Xiaoyin Wu ◽  
Ying Zhao ◽  
Shengliang Chen ◽  
Chung Owyang

Ghrelin receptors are present in the central nervous system. We hypothesized that ghrelin released from the stomach acts as an endocrine substance and stimulates brain stem vagovagal circuitry to evoke pancreatic secretion. In an in vivo anesthetized rat model, an intravenous infusion of ghrelin at doses of 5, 10, and 25 nmol increased pancreatic protein secretion from a basal level of 125 ± 6 to 186 ± 8, 295 ± 12, and 356 ± 11 mg/h, respectively. Pretreatment with atropine or hexamethonium or an acute vagotomy, but not a perivagal application of capsaicin, completely abolished pancreatic protein secretion responses to ghrelin. In conscious rats, an intravenous infusion of ghrelin at a dose of 10 nmol resulted in a 2.2-fold increase in pancreatic protein secretion over basal volume. Selective ablation of the area postrema abolished pancreatic protein secretion stimulated by intravenous infusion of ghrelin but did not alter the increase in pancreatic protein secretion evoked by diversion of bile-pancreatic juice. Immunohistochemical staining showed a marked increase in the number of c-Fos-expressing neurons in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus after an intravenous infusion of ghrelin in sham-lesioned rats; selective ablation of the area postrema eliminated this increase. In conclusion, ghrelin stimulates pancreatic secretion via a vagal cholinergic efferent pathway. Circulating ghrelin gains access to the brain stem vagovagal circuitry via the area postrema, which represents the primary target on which peripheral ghrelin may act as an endocrine substance to stimulate pancreatic secretion.


2005 ◽  
Vol 289 (5) ◽  
pp. E892-E899 ◽  
Author(s):  
Pu-Qing Yuan ◽  
Hong Yang

Hypo- or hyperthyroidism is associated with autonomic disorders. We studied Fos expression in the medullary dorsal motor nucleus of the vagus (DMV), nucleus tractus solitarii (NTS), and area postrema (AP) in four groups of rats with different thyroid states induced by a combination of drinking water and daily intraperitoneal injection for 1–4 wk: 1) tap water and vehicle; 2) 0.1% propylthiouracil (PTU) and vehicle; 3) PTU and thyroxine (T4; 2 μg/100 g); and 4) tap water and T4 (10 μg/100 g). The numbers of Fos immunoreactive (IR) positive neurons in the DMV, NTS, and AP were low in euthyroid rats but significantly higher in the 4-wk duration in hypothyroid rats, which were prevented by simultaneous T4 replacement. Hyperthyroidism had no effect on Fos expression in these areas. There were significant negative correlations between T4 levels and the numbers of Fos-IR-positive neurons in the DMV ( r = −0.6388, P < 0.008), NTS ( r = −0.6741, P < 0.003), and AP ( r = −0.5622, P < 0.004). Double staining showed that Fos immunoreactivity in the DMV of hypothyroid rats was mostly localized in choline acetyltransferase-containing neurons. Thyroid hormone receptors α1 and β2 were localized in the observed nuclei. These results indicate that thyroid hormone influences the DMV/NTS/AP neuronal activity, which may contribute to the vagal-related visceral disorders observed in hypothyroidism.


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