Biomedical subjects

A C Bonham

Publications and source records attributed to A C Bonham.

At least 37 records · Page 2Linked to original sources

PubMed1996

Substance P contributes to rapidly adapting receptor responses to pulmonary venous congestion in rabbits.

1. This study tested the hypothesis that substance P stimulates rapidly adapting receptors (RARs), contributes to the increase in RAR activity produced by mild pulmonary congestion, and evokes an augmented response from RARs when combined with near-threshold levels of pulmonary congestion. 2. RAR activity, peak tracheal pressure, arterial blood pressure and left atrial pressure were measured in paralysed, anaesthetized and ventilated rabbits. Substance P was given i.v. in one-half log incremental doses to a maximum of 3 micrograms kg-1. Mild pulmonary congestion was produced by inflating a balloon in the left atrium to increase left atrial pressure by 5 mmHg. Near-threshold levels of pulmonary congestion were produced by increasing left atrial pressure by 2 mmHg. 3. Substance P produced dose-dependent increases in RAR activity. The highest dose given increased the activity from 1.3 +/- 0.5 to 11.0 +/- 3.1 impulses bin-1. Increases in left atrial pressure of 5 mmHg increased RAR activity from 3.8 +/- 1.4 to 14.7 +/- 3.9 impulses bin-1. Blockade of NK1 receptors with CP 96345 significantly attenuated RAR responses to substance P and to mild pulmonary congestion. 4. Doses of substance P, which alone had no effect, stimulated the RARs when delivered during near-threshold levels of pulmonary congestion. 5. The findings suggest that substance P augments the stimulatory effect of mild pulmonary congestion on RAR activity, most probably by enhancing hydraulically induced microvascular leak.

Animals↗

PubMed1996

Sidestream smoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs.

We determined the effect of sidestream tobacco smoke (SS) exposure on responses of lung rapidly adapting receptors (RARs), peak tracheal pressure (Ptr), and arterial blood pressure (ABP) to substance P in young guinea pigs. Guinea pigs were exposed to SS or filtered air from day 8 to days 41-45 of life. They were then anesthetized and given three doses of intravenous substance P (1.56-4.94 nmol/kg). SS exposure augmented substance P-evoked increases in RAR activity (P = 0.029 by analysis of variance) but not substance P-evoked increases in peak Ptr or decreases in ABP. Neurokinin 1-receptor blockade (CP-96345, 400 nmol/kg) attenuated substance P-evoked increases in RAR activity (P = 0.001) and ABP (P = 0.009) but not in peak Ptr (P = 0.06). This chronic exposure to SS in young guinea pigs exaggerates RAR responsiveness to substance P. The findings may help explain the increased incidence of airway hyperresponsiveness and cough in children chronically exposed to environmental tobacco smoke.

Adaptation, Physiological↗

PubMed1995

Lung congestion augments the responses of cells in the rapidly adapting receptor pathway to cigarette smoke in rabbit.

1. We examined the effects of cigarette smoke, inhaled alone and during mild pulmonary venous congestion, on the activity of fifty-three neurones in the nucleus tractus solitarii (NTS) that were excited by input from pulmonary rapidly adapting receptors (RAR). Ten neurones excited by slowly adapting stretch receptors (SAR) were also studied. 2. Extracellular recordings of RAR-activated neurones were recorded in alpha-chloralose anaesthetized rabbits. Smoke from low- and high-nicotine cigarettes was delivered through a ventilator. Mild pulmonary venous congestion was produced by inflating a balloon in the left atrium. 3. Inhalation of three breaths of smoke from low-nicotine cigarettes increased the activity of fifty-one out of fifty-three RAR-activated neurones from 5.9 +/- 1.0 to 14.4 +/- 2.1 spikes breath-1 (P < 0.05). 4. The responses of fifteen neurones were compared with smoke inhaled alone or during mild pulmonary venous congestion. Smoke alone increased unit activity from 6.8 +/- 2.3 to 12.6 +/- 3.7 spikes breath-1 (P < 0.05). Small increases in left atrial pressure (2.0 +/- 0.5 mmHg) had no effect on baseline unit activity (7.6 +/- 2.11 vs. 7.7 +/- 2.3 spikes breath-1; P > 0.05), but enhanced the responses to smoke, increasing the activity from 7.6 +/- 2.1 to 17.1 +/- 4.8 spikes breath-1 (P < 0.05). The response was greater than to smoke alone (P < 0.05). 5. Of ten SAR-activated neurones, seven failed to respond to inhaled cigarette smoke, two were excited and one was inhibited. Pulmonary venous congestion had no effect on the unit activity before and after smoke (n = 4 neurones). 6. We conclude that smoke-evoked excitation of RAR lower-order neurones is augmented by pulmonary venous congestion.

Animals↗

PubMed1995

Neurotransmitters in the CNS control of breathing.

This review summarises our current understanding of the neurotransmitters involved in the generation, transmission and modulation of respiratory rhythm. The principal neurotransmitters involved in generating and transmitting respiratory rhythm include glutamate, GABA, and glycine. Glutamate acts primarily at non-NMDA receptors within the networks to generate respiratory rhythm in neonatal in vitro preparations, but it may also engage NMDA receptors in mature intact animals. Glutamate may likewise act as presynaptic AP-4 metabotropic receptors to fine tune its own release in the transmission of respiratory rhythm to the phrenic motoneurones. The role of other metabotropic receptors in rhythmogenesis is not known. GABA (primarily by acting at GABAA receptors), as well as glycine, transmit phasic waves of inhibition within the primary respiratory network. Neuroactive agents synthesized outside the primary network may shape the final expression of the basic rhythm. The most studied inputs originate in the pons and from the slowly adapting pulmonary stretch receptors (SAR). Both of these inputs contribute to the transition from inspiration to expiration. Pontine mechanisms rely on excitatory amino acid activation of NMDA receptors, while SAR pathways utilize non-NMDA receptors. Serotonin has also been implicated in regulating respiratory rhythm, possibly via serotonergic projections originating in the raphe nuclei. The amine has diverse effects on respiratory neuronal activity; the most consistent effect appears to be an augmentation of phrenic motoneuronal at the level of the spinal cord. Substance P regulates respiratory activity by acting in the CNS and on peripheral sensory receptors. Centrally, substance P largely augments respiration, by increasing respiratory rhythm in neonatal in vitro preparations and also by increasing tidal volume in the intact animal. Substance P is also released by carotid chemoreceptor afferents during hypoxia. Opioids are well known to decrease respiration; the central mechanism involves the suppression of baseline inspiratory neuronal activity and possibly the blunting of glutamate-evoked increases in inspiration drive.

Central Nervous System↗

PubMed1995

Role of spinal NK1 receptors in cardiovascular responses to chemical stimulation of the gallbladder.

The present study examined the role of substance P (SP) as a sensory neurotransmitter in cardiovascular responses to bradykinin applied on the gallbladder. Experiments were performed in anesthetized cats in which sympathetic chains were transected at the T5-T6 level, and the tip of the intrathecal catheter was positioned at T6-T7 to limit the injectate between T6 and L2. Bradykinin (10 micrograms/ml) was applied onto the gallbladder before and after intrathecal injection of [D-Pro2,D-Phe7,D-Trp9]SP (100-200 micrograms, NK1/NK2-receptor antagonist), CP-99,994 (50-100 micrograms, selective NK1 antagonist), MEN-10,376 (100-500 micrograms, selective NK2 antagonist), or vehicle. Intrathecal injection of NK1 but not NK2 antagonist significantly reduced increases in mean arterial pressure, heart rate, and maximal rate of left ventricular pressure change by 28 +/- 2 mmHg (33 +/- 4%), 4 +/- 1 beats/min (42 +/- 5%), and 497 +/- 46 mmHg/s (36 +/- 4%), respectively. Intrathecal injection of NK1 or NK1/NK2 antagonist had no effect on cardiovascular responses evoked by electrical stimulation in the rostral ventral lateral medulla. These data suggest that endogenous SP, acting as a sensory neurotransmitter, is involved in the excitatory cardiovascular reflex caused by chemical stimulation of the gallbladder through its action on NK1 receptors in the spinal cord.

Animals↗

PubMed1995

Pulmonary venous congestion augments respiratory motoneuronal responses to cigarette smoke in rabbit.

We examined the effects of cigarette smoke inhaled during subthreshold pulmonary venous congestion (sPVC) on phrenic nerve (PN) and unit activity in the ventral respiratory group in rabbits. sPVC was achieved by inflating a balloon in the left atrium. Inhalation of low-nicotine cigarette smoke produced initial prolonged bursts in 34 (19 bulbospinal) out of 43 inspiratory (I) cells and in PN. Smoke decreased the activity of 29 out of 36 expiratory (E) cells (27 of 32 early E and 2 of 4 late E). The prolonged PN bursts occasionally progressed to doublets superimposed over regularly occurring PN bursts. sPVC augmented the smoke effects: I cells displayed greater increases in spikes/burst (27 vs. 12%; P = 0.02) and burst duration (42 vs. 20%; P = 0.02) and greater decreases in interburst interval (34 vs. 10%; P < 0.02); PN displayed greater increases in I time (40 vs. 27%; P < 0.05), greater decreases in E time (18 vs. 26%; P < 0.05), and a greater incidence and duration of time of PN doublets (29 +/- 9 vs. 9 +/- 4 s; P < 0.03); E cells displayed greater decreases in spikes/burst (43 vs. 29%; P = 0.01) and burst durations (35 vs. 18%; P < 0.01). Smoke-induced respiratory changes may be exaggerated during sPVC.

Animals↗

PubMed1995

Exposing young guinea pigs to sidestream tobacco smoke decreases rapidly adapting receptor responsiveness.

We exposed 21 young guinea pigs to 5 wk of either sidestream tobacco smoke (SS) or filtered air (FA). The exposure started on day 8 of life and ended at 41-45 days of life. The animals were then anesthetized, and lung rapidly adapting receptor (RAR) and slowly adapting receptor (SAR) activities and peak tracheal pressure (TP) were examined in response to mainstream smoke. SS exposure did not alter baseline RAR activity. Low-nicotine smoke increased RAR activity in the FA but not in the SS group. High-nicotine smoke increased RAR activity in both groups but more so in the FA than in the SS group. Baseline TP was lower in the SS group. Both low- and high-nicotine smoke increased TP but more so in the FA than in the SS group. The increase in RAR activity preceded the increase in TP. SS exposure increased baseline SAR activity but did not affect the variable responses of SARs to low- and high-nicotine smoke. We suggest that exposing guinea pigs to SS during development diminishes the responsiveness of RARs to acute inhalation of mainstream smoke.

Administration, Inhalation↗

PubMed1994

Effect of pulmonary lymphatic obstruction on respiratory rate and airway rapidly adapting receptor activity in rabbits.

1. The effects on respiratory rate of obstruction of pulmonary lymph flow, reduction of plasma protein concentration and a combination of the two procedures were examined in anaesthetized rabbits. The former was achieved by raising the pressure in a pouch created from the right external jugular vein and the latter by batch plasmapheresis. 2. In spontaneously breathing rabbits, neither pulmonary lymphatic obstruction (n = 6) nor plasmapheresis (n = 5) produced a significant change in respiratory rate. However, their combination (n = 8) produced a significant increase in respiratory rate (P < 0.05). 3. Cooling of the cervical vagi to 8-9 degrees C (n = 4) and vagotomy (n = 7) abolished this response. 4. There was a significant increase in the activity of the airway rapidly adapting receptors (RARs; n = 9) during pulmonary lymphatic obstruction, plasmapheresis and their combination (P < 0.05). 5. It is concluded that in the rabbit, obstruction of lymphatic drainage from the lung after plasmapheresis causes a reflex increase in respiratory rate. The afferent pathway for this reflex response lies in the vagus nerve and the RARs are likely to be the receptors involved in this response.

Action Potentials↗

PubMed1994

Area postrema excites and inhibits sympathetic-related neurons in rostral ventrolateral medulla in rabbit.

This study investigated the effects of area postrema stimulation on the activity of cardiovascular-related neurons in the rostral ventrolateral medulla and determined whether the effects were mediated by cell bodies. Results are based on recordings of extracellular spikes from 113 neurons in 37 alpha-chloralose- or pentobarbital sodium-anesthetized rabbits. Single sequential stimuli evoked an excitation (onset, 22 +/- 8 ms; duration, 20 +/- 14 ms) followed by an inhibition (onset, 53 +/- 21 ms; duration, 127 +/- 82 ms) in 1) 58 neurons with discharge patterns that were correlated with sympathetic nerve activity (determined by spike-triggered averaging) and with the cardiac cycle (determined by post-R wave-triggered histograms) and that were inhibited by increasing arterial pressure and 2) 27 neurons that exhibited a cardiac rhythm but not a sympathetic rhythm. Area postrema-evoked excitation and inhibition were markedly attenuated by kainic acid injections in area postrema, suggesting that both inputs were derived from cell bodies. The results suggest that area postrema neurons may modulate the activity of medullary neurons in the baroreflex-sympathetic arc as well as neurons in other networks that share baroreceptor input but may not be related to sympathetic nerve activity.

Animals↗

PubMed1994

Pulmonary congestion enhances responses of lung rapidly adapting receptors to cigarette smoke in rabbit.

We examined the effects of low-nicotine cigarette smoke, pulmonary venous congestion, and their combination on the activity of rapidly (RAR) and slowly adapting receptors (SAR) in anesthetized rabbits. Pulmonary venous congestion was achieved by inflating a balloon in the left atrium to increase left atrial pressure. We examined smoke effects on RARs (averaged over 15 breaths) at baseline left atrial pressure and at subthreshold and suprathreshold increases in left atrial pressure. At baseline, smoke significantly increased RAR activity from 12.1 +/- 4.2 to 16.2 +/- 4.2 impulses/breath (P < 0.05). At subthreshold increases in left atrial pressure (2.9 +/- 0.6 mmHg), smoke produced larger increases in RAR activity (12.3 +/- 3.3 to 22.5 +/- 4.1 impulses/breath; P < 0.05). Suprathreshold increases in left atrial pressure (9.2 +/- 1.1 mmHg) alone increased RAR activity from 10.9 +/- 3.2 to 19.8 +/- 5.9 impulses/breath (P < 0.05). Smoke had no additional effect (22.3 +/- 4.8 impulses/breath; P > 0.05). There was, however, a transient increase in RAR activity (1st 3 breaths of smoke) under all three conditions. Of nine SARs examined, only two were stimulated by smoke. We conclude that in the rabbit smoke-induced stimulation of RARs is augmented by mild pulmonary venous congestion. of RARs is augmented by mild pulmonary venous congestion.

Adaptation, Physiological↗

PubMed1993

Pulmonary stretch receptor afferents activate excitatory amino acid receptors in the nucleus tractus solitarii in rats.

1. The goal of the present study was to identify potential neurotransmitter candidates in the Breuer-Hering (BH) reflex pathway, specifically at synapses between the primary afferents and probable second-order neurones (pump cells) within the nucleus tractus solitarii (NTS). We hypothesized that if activation of specific receptors in the NTS is required for production of the BH reflex, then (1) injection of the receptor agonist(s) would mimic the reflex response (apnoea), (2) injection of appropriate antagonists would impair the apnoea produced by either lung inflation or agonist injection, and (3) second-order neurones in the pathway would be excited by either lung inflation or agonists while antagonists would prevent the response to either. 2. Studies were carried out either in spontaneously breathing or in paralysed, thoracotomized and ventilated rats in which either diaphragm EMG or phrenic nerve activity, expired CO2 concentration and arterial pressure were continuously monitored. The BH reflex was physiologically activated by inflating the lungs. 3. Pressure injections (0.03-15 pmol) of selective excitatory amino acid (EAA) receptor agonists, quisqualic acid (Quis) and N-methyl-D-aspartic acid (NMDA) into an area of the NTS shown previously to contain neurones required for production of the BH reflex produced dose-dependent apnoeas that mimicked the response to lung inflation. Injection of substance P (0.03-4 pmol) did not alter baseline respiratory pattern. 4. Injections of the EAA antagonists, kynurenic acid (Kyn; 0.6-240 pmol), 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the BH region of the NTS reversibly impaired the apnoea produced by lung inflation. All three antagonists reduced or abolished the apnoeas resulting from injection of Quis or NMDA, and slowed baseline respiratory frequency. In contrast, injections of the highly selective NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acids (AP5), in doses sufficient to block the apnoeic response to NMDA, neither altered the reflex apnoea evoked by lung inflation nor the baseline respiratory pattern. 5. Pump cells located within the BH region were excited by pressure injections of the broad spectrum EAA agonist, DL-homocysteic acid (DLH). Kyn reversibly blocked the excitation of pump cells in response to either lung inflation or DLH injection. 6. These findings suggest that EAAs mediate primary afferent excitation of second-order neurones in the Breuer-Hering reflex pathway, primarily through the activation of non-NMDA EAA receptor subtypes.

Amino Acids↗

PubMed1993

Area postrema and aortic or vagal afferents converge to excite cells in nucleus tractus solitarius.

Area postrema neurons enhance baroreflex function, perhaps by augmenting baroreceptor afferent processing in the nucleus tractus solitarius (NTS). If so, NTS neurons should receive convergent excitatory inputs from area postrema neurons and baroreceptors. The aims of this study were to record extracellular activity of NTS neurons to determine whether 1) area postrema and aortic baroreceptor afferents converged in NTS, 2) area postrema and vagal afferents converged in NTS, and 3) the convergent inputs were facilitative. Studies were performed in pentobarbital sodium- or alpha-chloralose-anesthetized rabbits. Forty-six of 194 NTS neurons received inputs from the area postrema and aortic depressor nerve. Twelve of the 23 inputs showed facilitative summation; unit response rate evoked by paired inputs (79%) doubled the predicted (calculated) response rate for simple addition (37%). Fifty-eight of 114 NTS neurons received excitatory inputs from the area postrema and vagus. Eleven of the 13 inputs showed facilitative summation; unit response to paired inputs (87%) doubled the predicted response (44%). Area postrema neurons may augment the processing of aortic and vagal inputs by NTS neurons and, hence, enhance the reflex output of these afferent pathways.

Animals↗

PubMed1991

Neurones in commissural nucleus tractus solitarii required for full expression of the pulmonary C fibre reflex in rat.

1. The pulmonary C fibre reflex, triggered by activating pulmonary C fibre endings in the lung, consists of rapid shallow breathing (which may be preceded by apnoea), bradycardia, and hypotension. The purpose of this work was to identify proximal synapses in this reflex. From pilot data, we hypothesized that neurones in a discrete region of the commissural nucleus in the nucleus tractus solitarii (NTS) are required for full expression of the pulmonary C fibre reflex. Studies were carried out in urethane-anaesthetized, unilaterally vagotomized, spontaneously breathing rats, in which diaphragm electromyogram, arterial pressure, and blood gases were measured. Phenyldiguanide (PDG) was injected in the right atrium to elicit the pulmonary C fibre reflex. Unilateral NTS injections were made through multibarrelled pipettes containing DL-homocysteic acid (DLH) to mimic the reflex, cobalt chloride to reversibly impair the reflex, and/or dye to mark the injection sites. 2. PDG (5-16 micrograms kg-1) injected in the right atrium of twenty-six rats produced the classic pulmonary C fibre reflex: a vagally mediated, rapid onset of rapid shallow breathing, bradycardia and hypotension. 3. Injection of DLH (3-12 nl of 20 mM for a total of 60-240 pmol) in the dorsomedial aspect of the commissural nucleus of the NTS in thirty rats mimicked the pulmonary C fibre reflex, producing rapid shallow breathing, hypotension, and a slight bradycardia. 4. Interruption of neuronal transmission by injecting cobalt chloride (15-30 nl of 100 mM) in the site where DLH produced rapid shallow breathing, reversibly impaired the rapid shallow breathing and bradycardia produced by right atrial injections of PDG in fifteen rats. The commissural region where DLH produced rapid shallow breathing and cobalt impaired the pulmonary C fibre reflex extended from 720-1100 microns caudal to the obex, 30-200 microns lateral to mid-line, and 200-600 microns ventral to the dorsal surface of the brain stem within the NTS. 5. Taken together, the results suggest that neurones within a discrete region in the dorsomedial commissural nucleus in caudal NTS are required for full expression of the pulmonary C fibre reflex.

Animals↗

PubMed1991

Coronary vasoconstriction during stimulation in hypothalamic defense region.

Previous studies have identified a site in lateral hypothalamus (LH) in which electrical stimulation elicits coronary vasoconstriction. We injected the retrogradely transported tracer Fast Blue to determine which brain regions project to LH. Projections to or through LH were found from the paraventricular nucleus (PVN) of the hypothalamus, bed nucleus of the stria terminalis (BNST), and dorsal raphe nucleus (DRN). In chloralose-anesthetized cats, electrical stimulation in DRN and BNST failed to increase coronary vascular resistance (CVR). However, stimulation lateral to PVN in the anterior hypothalamic area (AHA), a region not labeled by the tracer, caused a transient decrease in coronary blood flow similar to that elicited from LH. The increase in CVR was accompanied by hemodynamic changes that are characteristic of the defense reaction including a cholinergically mediated decrease in hindquarter vascular resistance. This response is likely due to activation of fibers of passage and not cell bodies, since cell bodies in the region were not retrogradely labeled and coronary vasoconstriction was not seen following microinjection of several excitatory amino acids into AHA. These data suggest that coronary vasoconstriction may be a component of the defense reaction elicited by electrical activation of AHA.

Amidines↗

PubMed1990

Neurones in a discrete region of the nucleus tractus solitarius are required for the Breuer-Hering reflex in rat.

1. The Breuer-Hering reflex consists of a shortening of inspiration and lengthening of expiration in response to afferent input from slowly adapting pulmonary stretch receptors (SAR). We hypothesized that neurones in a discrete region of the nucleus tractus solitarius (NTS) are required for producing the reflex. Accordingly, the present studies were undertaken to: (1) identify sites in the NTS in which chemical excitation of neurones inhibited phrenic nerve discharge in a manner consistent with SAR activation, (2) determine whether localized interruption of synaptic transmission prevented the Breuer-Hering reflex, and (3) determine whether these regions contained pump cells and SAR terminal afferents. Studies were carried out in urethane-anaesthetized rats. 2. Injection of picomoles of an excitatory amino acid, DL-homocysteic acid (DLH), in the NTS, at the rostrocaudal level of the area postrema and immediately medial to the tractus solitarius, silenced phrenic nerve activity similarly to that expected from SAR activation. These apnoeas lasted from 3 to 43 s and were produced with little or no change in arterial pressure or heart rate. 3. The Breuer-Hering reflex, physiologically activated by maintaining lung inflation, was transiently impaired by interruption of synaptic transmission following injections of cobalt chloride in the DLH-responsive region. 4. Pump cell (SAR interneurone) and SAR afferent activity were recorded at the site in which DLH produced apnoea. 5. Taken together, the results of chemical excitation, interruption of synaptic transmission and extracellular recording, suggest that cells within a discrete region of the NTS, probably pump cells, are necessary for the production of the Breuer-Hering reflex.

Action Potentials↗

PubMed1990

Connections between hypothalamus and medullary reticular formation mediate coronary vasoconstriction.

We have recently identified discrete sites within the lateral hypothalamus and medullary reticular formation that, when stimulated electrically, produce neurally mediated coronary vasoconstriction. This study examined whether these sites are part of the same coronary vasomotor pathway. The neuronal tracing dye fast blue was injected in cats into the coronary vasoconstrictor site within medullary reticular formation. Fluorescence microscopy revealed major afferent projections originating from within the same region of midbrain ventrolateral periaqueductal gray that receives projections from lateral hypothalamus. To determine the functional importance of the proposed connections between the hypothalamic and medullary sites, anesthetized cats were prepared for continuous hemodynamic measurements. Constant current electrical stimulation within lateral hypothalamus produced significant increases in heart rate (21 +/- 6%), arterial pressure (11 +/- 3%), and femoral (36 +/- 18%) and coronary resistances (14 +/- 9%) with no change in coronary flow velocity (-1.1 +/- 2.5%). After beta-adrenoreceptor blockade, significantly greater increases in arterial pressure (35 +/- 8%) and coronary resistance (39 +/- 5%) with transient decreases in coronary flow velocity (21 +/- 6%) were seen. Microinjections of lidocaine into the medullary site blocked coronary constriction produced by lateral hypothalamic stimulation (39 +/- 5% increase in coronary resistance to electrical stimulation before and 2.4 +/- 2% increase after lidocaine in medullary reticular formation). These data provide evidence that specific regions of lateral hypothalamus and medullary reticular formation are part of a common central vasomotor projection that mediates coronary vasoconstriction in addition to other hemodynamic effects.

Amidines↗

PubMed1989

Cardiorespiratory effects of DL-homocysteic acid in caudal ventrolateral medulla.

We carried out experiments in urethan-anesthetized rats to determine 1) whether increasing the activity of small groups of neurons in the caudal ventrolateral medulla (CVLM) by injecting picomoles of an excitatory amino acid altered cardiovascular and/or respiratory homeostasis and 2) whether the depressor responses after chemical excitation in the CVLM were elicited only from the immunohistochemically identified catecholamine-containing cell group. In discrete sites in the CVLM, unilateral injections of 1-12 nl (20-240 pmol) of DL-homocysteic acid (DLH; 20 mM, pH 7.4) selectively or concomitantly inhibited arterial pressure, heart rate, and diaphragm electromyogram (EMG) activity. In the region in which chemical excitation slowed breathing, units were recorded extracellularly that discharged with respiratory periodicity. Sites where the smallest volumes of DLH decreased arterial pressure were located outside the immunohistochemically identified DBH-positive cell bodies. These data suggest that either the same or neighboring neurons in the CVLM are involved in the central neural circuitry for both cardiovascular and respiratory control and that cells other than the catecholaminergic cell group are important in medullary depressor responses.

Animals↗

PubMed1989

Characterization of coronary vasoconstrictor site in medullary reticular formation.

The importance of sympathetic neural influences in regulating coronary blood flow has been well established. However, central nervous system pathways responsible for these effects are largely unknown. In a feline model, we have identified a site in medullary reticular formation that may play a role in neural control of the coronary circulation. Changes in heart rate (HR), mean arterial pressure (AP), Doppler coronary flow velocity (CBFV), and femoral flow velocity (FBFV) were measured in 67 anesthetized cats. Electrical stimulation in a specific region of the right medullary lateral reticular formation produced elevations in HR (12 +/- 2% from 156 beats/min), AP (41 +/- 6% from 83 mmHg), CBFV (33 +/- 7%), and femoral vascular resistance index (136 +/- 27%). After beta-adrenergic blockade (propranolol), a transient (5-15 s) stimulus-induced decrease in CBFV was observed in 67% of animals, with a 55 +/- 6% increase in coronary vascular resistance index, not the result of autoregulation. Ipsilateral stellate ganglionectomy or systemic alpha 1-adrenergic blockade abolished the CBFV decrement. Microinjection of L-glutamate into this medullary region failed to elicit either pressor or coronary vasomotor responses. It is concluded that electrical stimulation in a specific site within medullary reticular formation produces neurogenic coronary vasoconstriction as part of a more generalized activation of central sympathetic fibers. This brain stem site may play an important role in reflex or behaviorally mediated coronary responses.

Adrenergic beta-Antagonists↗