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Biomedical subjects

R A Gillis

Publications and source records attributed to R A Gillis.

At least 19 recordsLinked to original sources
PubMed1992

Additive myocardial depressant effects of cocaine and ethanol.

Although significant morbidity and mortality have been associated with the combined use of cocaine and ethanol, the cardiovascular effects of this combination are unknown. In this study, the effect of ethanol on cocaine-induced cardiovascular alterations was examined in two groups (n = 8 each) of dogs, which were randomized to receive either ethanol (1.68 gm/kg intravenously) or saline solution and cocaine (2 mg/kg intravenously). Ethanol had no effect on heart rate, mean arterial pressure, or rate-pressure product; but it increased ventricular end-diastolic pressure (p < 0.05), reduced coronary diameter (p < 0.02), and decreased ejection fraction by 16% +/- 4% (p < 0.005) from baseline. Cocaine produced increases in mean arterial pressure, rate-pressure product, and left ventricular end-diastolic pressure that were similar in both groups. After administration of cocaine, left ventricular ejection fraction decreased 16% +/- 2% (p < 0.001) from the baseline value in controls and 32% +/- 5% (p < 0.0002 vs baseline; p < 0.01 vs controls) in the ethanol group. Coronary diameter decreased (p < 0.05) in both groups after administration of cocaine; however, there was no difference between groups in the response of coronary circulation to cocaine. Cocaine and ethanol depress myocardial function, and their effects are additive. Failure of ethanol to enhance cocaine-induced coronary vasoconstriction suggests that the additive myocardial depressant effect of this combination is not related to ischemia but rather to a direct toxic effect of these drugs. Individuals who combine ethanol and cocaine may be at increased risk of hemodynamic compromise.

Animals↗
PubMed1992

Effects of thyrotropin-releasing hormone on neurons in rat dorsal motor nucleus of the vagus, in vitro.

We sought to characterize the excitatory effect of thyrotropin-releasing hormone (TRH) in dorsal motor nucleus of the vagus (DMV) motoneurons by using the patch-clamp technique in rat brain stem slices. In our initial studies we used the cell-attached recording configuration using concentrations of TRH from 1 to 30 microM. Exposure of DMV motoneurons to TRH resulted in a concentration-related increase in spontaneously occurring action potential firing rate. This was observed in 63 of 85 DMV neurons (75%) tested and was unrelated to their location rostral or caudal to the obex. Invariably, desensitization occurred to the excitatory effect of TRH. Subsequent experiments using whole cell recordings in the current-clamp mode confirmed that TRH excites DMV neurons located both rostral and caudal to the obex. In the current-clamp configuration, TRH produced depolarization; i.e., 30 microM TRH elicited a depolarization of 8.7 +/- 3.2 mV (P < 0.05, n = 7). Studies using whole cell current recordings in voltage-clamp mode indicated that TRH in a concentration-dependent manner produces a small inward current that is associated with a decrease in the input resistance of -42.5 +/- 15.6 M omega (TRH 30 microM). TRH-induced inward current was also present under conditions of inhibition of synaptic transmission (i.e., in the presence of tetrodotoxin and cobalt). We also found that TRH reduced in a concentration-dependent manner both the fast transient A-type K+ current (IA) and the Ca(2+)-dependent afterhyperpolarizing current (IAHP). Using the extracellular recording technique in the cell-attached configuration, we investigated whether any part of TRH-induced increase in firing rate was due to an increase in the synaptic release of L-glutamate or acetylcholine. Prior exposure of DMV neurons to either kynurenic acid or to atropine did not antagonize any of the excitatory effect of TRH. Finally, we observed that addition of 30 microM TRH to the perfusing solution produced an increase in spontaneously occurring excitatory postsynaptic currents (EPSCs). This occurred without any change in the amplitude of EPSCs. These results indicated that TRH-induced increase in firing of DMV neurons is due to direct postsynaptic effects to activate an inward cationic current and to counteract IA and IAHP, as well as a presynaptic effect to increase the frequency of EPSCs.

Animals↗
PubMed1992

A beta-carboline derivative (ZK 93426) counteracts the cardiorespiratory depressant effects of intravenous midazolam.

The purpose of this study was to test the effects of the new beta-carboline ZK 93426 on midazolam-induced cardiorespiratory depression. Seven pentobarbital-anesthetized (35 mg/kg i.p.) cats were treated with intravenous midazolam (2 mg/kg) while monitoring the respiratory minute volume (VE), tidal volume, respiratory rate, blood pressure, heart rate and expired CO2. Midazolam caused significant decreases in VE (p less than 0.05) and blood pressure (p less than 0.05). ZK 93426 (5 mg/kg i.v.) antagonized these effects and produced significant increases in VE and blood pressure that resulted in the return of these variables to premidazolam control values. In 4 animals with morphine-induced respiratory depression, intravenous ZK 93426 failed to antagonize the respiratory effects of morphine. Administration of intravenous ZK 93426 alone to 4 pentobarbital-anesthetized animals also failed to produce significant changes in cardiorespiratory activity. We conclude that ZK 93426 is effective in counteracting the cardiorespiratory depressant effects of midazolam and that these effects appear to be specific. The present data suggest that this compound may be useful for the treatment of benzodiazepine oversedation and overdose.

Animals↗
PubMed1992

Gamma-aminobutyric acid type A receptor blockade at the intermediate area of the ventral surface of the medulla counteracts the cardiorespiratory depression produced by intravenous midazolam.

Intravenous administration of midazolam (2 mg/kg) to 8 pentobarbital-anesthetized cats produced a significant decrease in minute ventilation, tidal volume, blood pressure and heart rate. Treatment with the gamma-aminobutyric acid (GABA) type A receptor antagonist bicuculline (10 micrograms/side) at the intermediate area of the ventral surface of the medulla (VSM) oblongata completely reversed the cardiorespiratory depressant effects of intravenous midazolam. In contrast, treatment with bicuculline at the same area failed to counteract the respiratory depressant effects of intravenous morphine (1 mg/kg). We conclude that the cardiorespiratory depressant effects of intravenously administered midazolam are due to enhancement of GABAergic transmission at the intermediate area of the VSM.

Animals↗
PubMed1992

Cocaine produces coronary artery vasoconstriction independent of an intact endothelium.

Studies have demonstrated that cocaine causes coronary vasoconstriction, but this has been unassociated with myocardial ischemia. Therefore, cocaine seems unlikely to precipitate myocardial infarction in the absence of potentiating factors. We hypothesized that injury to coronary endothelium could potentiate cocaine-induced coronary vasoconstriction by decreasing EDRF. The effect of cocaine on LAD diameter was measured in dogs subjected to coronary endothelial denudation and compared with that in a non-denuded control group. Endothelial denudation was accomplished by abrasion with an inflated angioplasty balloon and confirmed in vivo by demonstrating a vasoconstrictive response to infused acetylcholine and by postmortem scanning electron microscopy. Cocaine produced a similar maximal reduction in LAD diameter in both groups. Thus, cocaine induces endothelium-independent coronary artery vasoconstriction. Failure of endothelial injury to potentiate the coronary vasoconstrictive effect by cocaine suggests that factors other than endothelial dysfunction may be important in pathogenesis of cocaine-associated myocardial infarction.

Acetylcholine↗
PubMed1991

Interaction between pressor and depressor areas in cat ventrolateral medulla.

The purpose of the present study was to investigate whether stimulation of the caudal depressor area (CA) in the medulla lowered blood pressure (BP) by enhancing GABA release at the intermediate pressor area (IA) of the medulla. Application of the excitotoxin kainic acid (KA; 40 mM solution) to the caudal area lowered BP as has been previously described (Gatti, et al., Brain Research, 330 (1985) 21-29). Subsequent IA application of the GABA receptor antagonists picrotoxin (100 micrograms/side) or bicuculline (10 micrograms/side) consistently reversed this hypotensive effect. Picrotoxin raised BP by 92 +/- 10 mmHg (n = 5) after KA while by itself, picrotoxin only increased BP by 23 +/- 7.0 mmHg (n = 3) when applied to the IA. This effect was significantly greater following KA application to the caudal area (P less than 0.05). Likewise, bicuculline raised BP by 74 +/- 8.7 mmHg (n = 7) following KA while by itself, bicuculline only increased BP by 24 +/- 8.2 mmHg when applied to the IA (n = 4). This also was significantly different. This potentiation was not seen with the glycine receptor antagonist, strychnine. These data indicate that there is a GABAergic input from the caudal to the intermediate ventral surface areas of the cat which is involved in the central control of BP.

Animals↗
PubMed1991

Evidence that cocaine slows cardiac conduction by an action on both AV nodal and His-Purkinje tissue in the dog.

The effects of intravenous cocaine (2 mg/kg) were tested on several indices of cardiac electrical activity in sedated dogs. These included sinus rate, PR, AH, and HV intervals; AV nodal effective refractory period (AVNERP); ventricular effective refractory period; QRS duration; and the QT interval. Cocaine induced significant changes in six control animals with an intact-functioning autonomic nervous systems. After pharmacologic autonomic blockade with propranolol plus propantheline, cocaine increased the PR interval (+ 11 +/- 4.0 ms, p less than 0.05), primarily by slowing conduction at the AV nodal level. However, with constant atrial pacing at a rate above the sinus cycle length, prolongation of both the AH and the HV intervals (+ 15 +/- 2.5 and 6.7 +/- 1.7 ms, respectively) occurred. There was also a significant increase in the AVNERP (+ 29 +/- 5.9 ms, p less than 0.05). Consistent with the observed rate-dependent HV prolongation, cocaine decreased the rate of rise of phase 0 of the transmembrane action potential of Purkinje fibers. These data indicate that cocaine impairs cardiac conduction by direct actions on AV nodal and His-Purkinje cells.

Action Potentials↗
PubMed1991

Excitation of neurons in the medullary raphe increases gastric acid and pepsin production in cats.

The nucleus raphe obscurus (NRO) has recently emerged as an important nucleus for excitation of gastric motor activity through projections to the dorsal motor nucleus of the vagus (DMV) [P. J. Hornby, C. D. Rossiter, R. L. White, W. P. Norman, D. H. Kuhn, and R. A. Gillis. Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21): G91-G96, 1990; and M. J. McCann, G. E. Herman, and R. C. Rogers. Brain Res. 486: 181-184, 1989]. A neurotransmitter thought to be involved in this NRO-DMV pathway is thyrotropin-releasing hormone (TRH), a peptide that excites gastric activity when microinjected into the DMV. The purpose of the present study was to determine whether gastric acid and pepsin secretion were altered by 1) activation of neurons in the NRO by microinjection of kainic cid and 2) microinjection of TRH into the DMV in chloralose-anesthetized cats. Microinjection of kainic acid into the NRO increased gastric acid secretion [baseline was 6 +/- 2 (mu eq) H+/15 min (n = 7) and increased to 8 +/- 2, 26 +/- 11 (P less than 0.05), and 21 +/- 7 mu eq/15 min (P less than 0.05) during the first, second, and third 15-min periods after microinjection, respectively]. Pepsin output also increased from a baseline of 287 +/- 67 pepsin units (PU) (n = 4) to 507 +/- 126 PU 15 min postinjection, 541 +/- 118 PU 30 min after injection (P less than 0.05), 608 +/- 92 PU 45 min after injection (P less than 0.05), and 700 +/- 156 PU 60 min postinjection (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Glutamate and GABA-mediated synaptic currents in neurons of the rat dorsal motor nucleus of the vagus.

We report the presence of excitatory and inhibitory spontaneous and evoked synaptic currents in the dorsal motor nucleus of the vagus (DMV) in the rat upon vagal and perivagal stimulation. Whole cell current-clamp recordings from anatomically identified DMV neurons in rat brain stem slices show that these neurons are capable of sustained slow-frequency action potential firing probably because of the presence of pacemaker current. Spontaneously occurring, tetrodotoxin-resistant miniature inhibitory and excitatory synaptic potentials were observed. Stimulation of the vagus mostly induced antidromic action potentials in DMV neurons. However, careful positioning of the stimulating electrode in the tissue surrounding the recording neuron, and sometimes in the vagus itself, was capable of evoking orthodromic-evoked mixed inhibitory-excitatory postsynaptic potentials, and eventually, action potentials. Whole cell voltage-clamp recordings of the synaptic currents corresponding to these synaptic potentials in the presence of pharmacological antagonists of the neurotransmitters gamma-aminobutyric acid (GABA), glutamate, and glycine receptor subtypes indicate that the inhibitory synaptic currents are mediated by GABA-activated Cl- channels, while the excitatory synaptic currents are due to activation of ionotropic glutamate receptors of the N-methyl-D-aspartic acid (NMDA) and non-NMDA subtypes.

Action Potentials↗
PubMed1991

The role of serotonin-1A receptor activation and alpha-1 adrenoceptor blockade in the hypotensive effect of 5-methyl-urapidil.

Our study had three purposes: 1) to determine whether 5-methyl-urapidil, topically applied to the ventrolateral medulla, produces hypotension by activating serotonin-1A (5-HT1A) receptors, 2) to determine whether 5-methyl-urapidil given i.v. produces hypotension in part by activating 5-HT1A receptors in the ventrolateral medulla, and 3) to determine the specific site within the ventrolateral medulla where 5-methyl-urapidil elicits a hypotensive response. In terms of the first purpose, 5-methyl-urapidil applied bilaterally to the intermediate area of the ventral surface of the medulla (1.2 micrograms/side) of chloralose-anesthetized cats produced a decrease in mean arterial pressure of -39 +/- 4 mm Hg (N = 8). Prior blockade of 5-HT1A receptors at this site with bilateral application of spiperone (30 micrograms/side) prevented the hypotensive effect of 5-methyl-urapidil (mean blood pressure now increased by 5 +/- 4 mm Hg). Pretreatment with the alpha-1 adrenoceptor antagonist, prazosin, did not prevent the hypotensive effect of 5-methyl-urapidil. In terms of the second purpose, spiperone applied bilaterally to the ventral surface of the medulla counteracted a significant portion of the hypotensive effect of 5-methyl-urapidil given by the i.v. route. The dose of 5-methyl-urapidil given intravenously was below the dose that produces alpha-1 adrenoceptor blockade. In terms of the third purpose, microinjection of 5-methyl-urapidil into central nervous system sites associated with the intermediate area was found to have its greatest hypotensive effect at the subretrofacial nucleus. Mean arterial pressure decreased by 74 +/- 14 mm Hg (N = 3) after bilateral microinjection of 25 ng of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1991

An excitatory amino acid(s) in the ventrolateral medulla is (are) required for breathing to occur in the anesthetized cat.

The purpose of the present study was to identify sites(s) in the ventrolateral medulla where excitatory amino acids are involved in respiratory control. For this purpose, the respiratory effects produced by bilateral microinjection of excitatory amino acid antagonist drugs were examined while tidal volume (Vt), respiratory rate (f), arterial blood pressure and heart rate were monitored in chloralose-anesthetized cats. Microinjection of kynurenic acid (12.5 nmol) into a site approximately 3 mm rostral to obex, 4 mm lateral to midline and 1.5 mm below the ventral surface produced a decrease in Vt (-20 +/- 2 ml), an increase in f (+20 +/- 3 breaths/min) and a decrease in respiratory minute volume (-108 +/- 19 ml/min) (n = 8). These changes progressed to apnea in each animal tested. No significant changes in blood pressure or heart rate were observed. To determine the excitatory amino acid receptor subtype(s) involved, antagonists of n-methyl-D-aspartate (NMDA) (3-[(RS)-carboxypiperazin-4-yl]-propyl-1-phosphoric acid (CPP] and non-NMDA [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] receptors were microinjected bilaterally into this site. In the case of CPP, three doses were studied (0.25 nmol, n = 4; 0.75 nmol, n = 3; 2.25 nmol, n = 2). All three doses produced similar decreases in Vt (-12 +/- 1, P less than .05; -10 +/- 1, P less than .05; and -16 +/- 5 ml, respectively) and increases in f (+14 +/- 2, P less than .05; +10 +/- 3, P less than .05; and +12 +/- 3 breaths/min, respectively). None of these animals exhibited apnea.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Cocaine acts in the central nervous system to inhibit sympathetic neural activity.

Cocaine was administered i.v. to decerebrate cats while monitoring cardiac preganglionic sympathetic nerve activity (SNA), arterial blood pressure (BP) and heart rate (HR). Cocaine, 4 mg/kg i.v., reduced SNA by 55 +/- 6%, but did not significantly affect BP or HR. Cocaine, in doses that were ineffective by the i.v. route, was administered into the vertebral artery and produced decreases in SNA, BP and HR in anesthetized cats. Administration of cocaine into the carotid artery was without effect. Topical administration of cocaine to the intermediate area of the ventrolateral medullary surface (25 micrograms/side) evoked hypotension and bradycardia. Nisoxetine, an inhibitor of norepinephrine uptake, applied bilaterally to the intermediate area (30 micrograms/side) exerted a similar hypotensive effect. Lidocaine administered in doses equivalent to those of cocaine had no significant effect on SNA when given i.v. or on BP when given into the vertebral artery. These results indicate that cocaine inhibits central sympathetic outflow and that the site of action appears to be in the hindbrain at a site that is reached by placement of the drug at the intermediate area of the ventrolateral medulla. The data also indicate that the mechanism of action of cocaine to inhibit sympathetic outflow may be unrelated to its local anesthetic action and may involve inhibition of catecholamine uptake in the ventrolateral medulla.

Animals↗
PubMed1991

Propranolol promotes cocaine-induced spasm of porcine coronary artery.

Case reports suggest that cocaine use is associated with acute myocardial infarction which may be due to coronary spasm. The present study reports the effect of cocaine on the isolated coronary artery. Ring segments were prepared from the porcine left anterior descending coronary artery and suspended in tissue baths under isometric conditions. Cocaine was ineffective by itself in promoting contraction, but a cumulative concentration-response curve was obtained in the presence of DL-propranolol (1.3 x 10(-6) M); D-propranolol failed to promote cocaine-induced vasoconstriction. The maximum contractile response to cocaine was one-third of the response to histamine and was in the same range as the response to U46619, prostaglandin F2 alpha and norepinephrine. Phenylephrine had a weak effect. In the presence of DL-propranolol, the vasoconstrictive effect of cocaine was subject to rapid tachyphylaxis. Prazosin (5 x 10(-9) M), also in the presence of DL-propranolol, significantly displaced the cocaine concentration-response curve to the right and diminished contractile force by one-half. We conclude that cocaine-induced coronary vasoconstriction elicited in the presence of DL-propranolol can be mediated through local adrenergic mechanisms involving beta receptor antagonism and activation of both alpha-1 and alpha-2 adrenoceptors.

Animals↗
PubMed1990

Distribution of neuropeptide Y-like immunoreactive perikarya and processes in the medulla of the cat.

Neuropeptide Y-like immunoreactive (NPY-LI) perikarya and processes have been identified in the medulla of the cat. NPY-LI perikarya were found in 4 regions; (1) the medial N. of the solitary tract (MNTS), (2) the lateral tegmental field (LTF), (3) the ventrolateral medullary surface (VLMS), and (4) in the spinal trigeminal nucleus. Tyrosine hydroxylase-like immunoreactive (TH-LI) neurons were also found in the first 3 regions noted above. NPY-LI and TH-LI neurons had a similar morphology and distribution. NPY-LI and TH-LI neurons were counted in sections from 3 representative levels of the medulla. NPY-LI cells were most numerous in the LTF, especially at the level of the area postrema and more rostrally. The lowest number of NPY-LI cells was seen in the MNTS, particularly at a level caudal to the area postrema. NPY-LI cells were at least 3-fold less numerous than TH-LI cells at all levels of the MNTS, but there was a 27-fold greater number of TH-LI neurons at a level of MNTS caudal to the area postrema. In the LTF, NPY-LI cells were 2- to 5-fold less common than TH-LI cells. Approximately equal numbers of NPY-LI and TH-LI cells were counted in the VLMS at the level of the area postrema and rostrally. These data indicate that the majority of TH-LI cells in the MNTS of the cat probably do not contain NPY as a co-transmitter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of cocaine on the coronary circulation and systemic hemodynamics in dogs.

This study investigated the effect of intravenous cocaine (0.5 to 2 mg/kg body weight) on the coronary circulation and systemic hemodynamics in closed chest sedated dogs. The role of alpha- and beta-adrenoceptor stimulation in mediating these effects was also investigated. Cocaine produced dose-dependent increases in mean arterial pressure and rate-pressure product. Although the lower doses of cocaine had no significant effect on the coronary circulation, the 2 mg/kg dose produced a 55 +/- 14% increase in coronary vascular resistance (p less than 0.05 versus baseline) and a 19 +/- 3% reduction in diameter of the left anterior descending coronary artery (p less than 0.05 versus baseline). Despite these potentially deleterious effects on the coronary circulation (occurring at a time of markedly increased myocardial oxygen demand), the electrocardiogram did not demonstrate ischemic changes and there was no myocardial lactate production. Cocaine-induced coronary vasoconstriction was abolished by pretreatment with the alpha-adrenoceptor antagonist phentolamine, but not by pretreatment with the beta-adrenoceptor antagonist propranolol. The findings that cocaine did not change systemic vascular resistance in dogs without adrenergic blockade, reduced systemic vascular resistance in dogs after alpha-blockade (p less than 0.05) and increased systemic vascular resistance in dogs after beta-blockade (p = 0.06) suggest that epinephrine (rather than norepinephrine) is primarily responsible for the peripheral vascular actions of cocaine. Thus, in this canine preparation with normal coronary arteries, cocaine produced vasoconstriction of both epicardial and coronary resistance vessels that was not associated with evidence of myocardial ischemia. The pharmacologic mechanism for the effect of cocaine on the coronary circulation is alpha-adrenoceptor stimulation, whereas systemic hemodynamic effects are mediated by combined alpha- and beta-adrenoceptor stimulation.

Animals↗
PubMed1990

Medullary raphe: a new site for vagally mediated stimulation of gastric motility in cats.

Thyrotropin-releasing hormone (TRH) is clearly implicated in the control of gastric function via interactions in the dorsal motor nucleus of the vagus (DMV) of the cat. The source of the TRH innervation of the DMV is important to determine because this region could be of importance in control of gastric function. TRH-immunoreactive (ir) neurons are located in the raphe obscurus (Ro), raphe pallidus (Rp), and raphe magnus (Rm). Retrograde tracer applied to the DMV resulted in the most numerous labeled neurons in the caudal Ro and Rp in the same region where TRH-ir neurons are located. To address the question whether DMV-projecting neurons in the raphe subnuclei play a role in control of gastric motility, the following experiments were performed in alpha-chloralose-anesthetized cats while recording pyloric motility and blood pressure. Microinjection of a cell body excitant L-glutamate (44-200 nl, 0.5 M) into the caudal Ro and Rp in 15 experiments produced significant increases in pyloric minute motility index (MMI) of 4.9 +/- 1.5 (from 1.6 +/- 0.7 preinjection to 6.5 +/- 1.8 postinjection, P less than 0.05). Mean blood pressure (MBP) decreased significantly in these animals by 12 +/- 7 mmHg (from 100 +/- 6 to 88 +/- 8 mmHg, P less than 0.05). Saline microinjection in the same sites in seven cases resulted in no significant change in pyloric MMI (-1.0 +/- 0.8) or MBP (-4 +/- 11 mmHg). In five of these experiments, a second microinjection of L-glutamate (132-240 nl) was performed into the caudal Ro and Rp after spinal cord transection. This resulted in a significant increase in pyloric MMI of 3.3 +/- 0.9 (from 1.0 +/- 0.5 preinjection to 4.3 +/- 1.1 postinjection, P less than 0.05) but no change in MBP (+1 +/- 1 mmHg). Bilateral vagotomy resulted in the abrupt cessation of the pyloric response to caudal Ro and Rp stimulation. Microinjection of L-glutamate into the rostral Rp and caudal Rm in nine experiments resulted in no significant changes in pyloric MMI (-0.4 +/- 0.8) or MBP (-10 +/- 11 mmHg). These data indicate that a population of neurons in the caudal raphe nuclei, which may contain TRH, project to the DMV. In addition, excitation of these neurons causes an increase in gastric motility that is not caused by inhibition of sympathetic outflow to the gut but rather by excitation of vagal neurons in the DMV.

Animals↗
PubMed1990

Control of lower esophageal sphincter pressure by two sites in dorsal motor nucleus of the vagus.

Our purpose was to determine the central vagal sites for regulating changes in lower esophageal sphincter (LES) pressure in the cat. Injection of the retrograde tracer, horseradish peroxidase, into the LES resulted in labeling of cells in the dorsal motor nucleus of the vagus (DMV), with the largest number of cells appearing in two areas, one area rostral to obex (1.5-4.0 mm) and one area caudal to obex (-0.5 to -1.5 mm). In alpha-chloralose-anesthetized cats, L-glutamic acid was microinjected into these areas and LES pressure, intragastric pressure, and stomach motility were monitored. Microinjection of L-glutamic acid into the rostral area resulted in significant increases in LES pressure (18.6 +/- 4.9 mmHg; P less than 0.05), pyloric motility (baseline minute motility increased from 5.7 +/- 2.2 to 14.5 +/- 3.9 postinjection; P less than 0.05) and stomach pressure (baseline of 16.9 +/- 2.3 mmHg increased to 23.8 +/- 3.7 mmHg postinjection; P less than 0.05). Microinjection of L-glutamic acid into the caudal area resulted in significant decreases in LES pressure (-14.3 +/- 5.8 mmHg; P less than 0.05) and intragastric pressure (-7.5 +/- 2.2 mmHg; P less than 0.05) with no significant changes in pyloric motility. Ipsilateral vagotomy abolished both sets of responses. These data indicate that excitatory and inhibitory control of LES and intragastric pressure are mediated by vagal efferent neurons located in two distinct sites in the DMV.

Animals↗