Cardiovascular responses and neurotransmission in the ventrolateral medulla during skeletal muscle contraction following transient middle cerebral artery occlusion and reperfusion

We hypothesized that static skeletal muscle contraction-induced systemic cardiovascular responses, and central glutamate/GABA release in rostral (RVLM) and caudal ventrolateral medulla (CVLM), would be modulated by cerebral ischemia. In sham-operated rats, a 2-min tibial nerve stimulation induced static contraction of the triceps surae, evoked pressor responses, increased glutamate in both the RVLM and CVLM, decreased GABA in the CVLM, and increased GABA in the RVLM. In rats with a temporary 90-min left middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion, pressor responses during muscle contractions were attenuated, as were glutamate within the left RVLM and left CVLM. Glutamate within the right RVLM and right CVLM were unaltered and similar to those in sham rats. In contrast, GABA increases during muscle contractions were enhanced in the left RVLM and CVLM but changes within the right CVLM and RVLM were similar to those in sham rats. These results indicate that unilateral ischemia increases ipsilateral GABA/glutamate ratios during muscle contraction in the RVLM. In contrast, opposite changes in ipsilateral glutamate and GABA release within the RVLM and CVLM were observed following a 90-min right-sided MCAO followed by 24 h reperfusion. However, cardiovascular responses during muscle contraction were depressed following such an ischemic brain injury. These data suggest that transient ischemic brain injury attenuates cardiovascular responses to static exercise via modulating neurotransmission within the ventrolateral medulla.     

Effects of nitric oxide and GABA interaction within ventrolateral medulla on cardiovascular responses during static muscle contraction

We hypothesized that nitric oxide (NO) has opposing roles in regulating cardiovascular responses within the rostral (RVLM) and caudal (CVLM) ventrolateral medulla by modulating release of gamma-aminobutyric acid (GABA). We have measured GABA concentrations within the RVLM and CVLM during increases in mean arterial pressure (MAP) and heart rate (HR) following a 2-min tibial nerve stimulation-evoked static muscle contraction before and after microdialysis of the NO precursor, L-arginine (1.0 microM), for 30 min, and after the NO inhibitor, L-NMMA (1.0 microM), for 30 min. In eight anesthetized rats, muscle contraction significantly increased MAP, HR and GABA levels within the RVLM area (from 0.53+/-0.09 to 1.22+/-0.10 ng/10 microl). Following microdialysis of L-arginine, muscle contraction augmented GABA levels (from 0.45+/-0.07 to 2.18+/-0.09 ng/10 microl) and attenuated changes in MAP and HR. Subsequent application of L-NMMA significantly decreased GABA levels (from 0.47+/-0.08 to 0.22+/-0.07 ng/10 microl) but potentiated MAP and HR responses to a muscle contraction. In contrast, muscle contraction significantly increased MAP and HR but decreased GABA concentrations within the CVLM (from 1.20+/-0.20 to 0.78+/-0.17 ng/10 microl). Following microdialysis of L-arginine, muscle contraction significantly attenuated GABA levels (from 1.34+/-0.19 to 0.33+/-0.10 ng/10 microl) and augmented changes in MAP and HR in response to muscle contraction. A subsequent microdialysis of L-NMMA into the CVLM reversed the effects of L-arginine. These results demonstrate that NO within the RVLM and CVLM differentially modulates cardiovascular responses during static muscle contraction and that NO influences exercise-induced cardiovascular responses by modulating GABA release within the ventrolateral medulla.     

Expression of Fos protein in adrenal preganglionic neurons following chemical stimulation of the rostral ventrolateral medulla of the rat

The ventrolateral medulla is known to be involved in the regulation of arterial blood pressure, especially via its connections with sympathetic preganglionic neurons (SPNs) mainly located in the intermediolateral nucleus of the spinal cord. It has been shown that stimulation of the rostral part of the ventrolateral medulla (RVLM) elicits a release of catecholamines from the adrenal medulla. The aim of the present study was to demonstrate the existence of a functional pathway between the RVLM and adrenal SPNs using the combination of a retrograde tract tracing technique (cholera toxin B subunit) with the immunohistochemical detection of Fos protein following the chemical stimulation of RVLM. The data obtained showed that: (1) chemical stimulation of the RVLM induced Fos immunoreactivity in the intermediolateral nucleus and particularly in SPNs projecting to the adrenal medulla; (2) along the thoracic segments T2-T12, 26.1% of retrogradely identified adrenal SPNs were Fos-immunoreactive with the greatest percentage (30.9%) in the T8 segment. These results favored a functional control of the RVLM on adrenal SPNs which may contribute to a substantial activation of the cardiovascular system via the release of adrenal catecholamines.     

Rostral ventrolateral medulla suppresses reflex bradycardia by the release of gamma-aminobutyric acid in nucleus tractus solitarii of the rat

We investigated the role of gamma-aminobutyric acid (GABA) in the nucleus tractus solitarii (NTS), the principal recipient of baroreceptor afferent fibers in the medulla oblongata, in the suppression of cardiac baroreceptor reflex (BRR) response by the rostral ventrolateral medulla (RVLM). Direct microinfusion via reverse microdialysis of L-glutamate (50 microM) into the RVLM promoted an inhibition of the BRR response, alongside an increase in the concentration of GABA in the dialysate collected from the ipsilateral NTS. Such an increase in GABA concentration in the NTS to RVLM activation was site-specific, as microinfusion of L-glutamate into areas outside the confines of RVLM resulted in no discernible change in GABA concentration in the dialysate of the NTS and minimal effect on the cardiac BRR response. The RVLM-induced BRR suppression of cardiac BRR response to microinjection into the bilateral RVLM of L-glutamate (1 nmol) was antagonized by administration into the bilateral NTS of the GABA(A) receptor antagonist, bicuculline methiodide (1 or 5 pmol), or the GABA(B) receptor antagonist, 2-hydroxy-saclofen (100 or 500 pmol). These results suggest that GABA released in the NTS may participate in cardiac BRR suppression induced by glutamatergic activation of the RVLM, via an action on both GABA(A) and GABA(B) receptor subtypes.     

Circulatory and respiratory responses to glutamate stimulation of the lateral parabrachial nucleus of the cat.

Electrical stimulation of the dorsal part of the lateral parabrachial nucleus (Pbl) induced a pressor response associated with a brief hyperpneic response, whereas glutamate stimulation induced no response, suggesting that the response to electrical stimulation may be due to excitation of passing fibers. Electrical stimulation of the lateral part of the Pbl induced a pressor and hyperpneic response, while glutamate stimulation induced either a pressor-depressor or single depressor response associated with a hyperpneic and polypneic response, suggesting that the response to electrical stimulation of the lateral part may be due to excitation of cell bodies. WGA-HRP study clarified that the cells in the region around the ventrolateral edge of the brachium conjunctivum project to the cells in the C1 area and subfacial cell group of the rostral ventrolateral medulla (RVLM), suggesting that the cells in this region may send a message to the sympathetic premotor and respiratory premotor cells in the RVLM. Inversely, the cells in the C1 area and the subfacial cell group project to the lateral part of the Pbl, suggesting mutual innervation between the Pbl and RVLM.     

Simultaneous glutamate and gamma-aminobutyric acid release within ventrolateral medulla during skeletal muscle contraction in intact and barodenervated rats.

The purpose of this study was to determine if baroreflex modulates cardiovascular responses and neurotransmitter release within rostral (RVLM) and caudal (CVLM) ventrolateral medulla during static contraction of skeletal muscle using anesthetized rats. We evoked cardiovascular responses by a static muscle contraction and measured simultaneous release of glutamate and gamma-aminobutyric acid (GABA) in both the RVLM and CVLM using microdialysis probes, two inserted bilaterally into the RVLM and two into the CVLM. In intact anesthetized rats, a muscle contraction increased release of glutamate concomitantly in both the RVLM and CVLM along with significant increases in heart rate and arterial blood pressure. In contrast, concentrations of GABA increased within the RVLM, but decreased significantly within the CVLM during the pressor response. These changes were due to contraction-evoked activation of muscle afferents since tibial nerve stimulation following muscle paralysis failed to evoke glutamate, GABA, or any cardiovascular changes. On the other hand, static muscle contractions in baroreceptor denervated rats augmented the increases in heart rate and blood pressure. Furthermore, muscle contraction significantly enhanced the release of glutamate in the RVLM but attenuated its release in the CVLM. In addition, concentrations of GABA within the RVLM were attenuated following a muscle contraction in denervated rats without any changes in GABA within the CVLM. These results demonstrate that the baroreceptors influence cardiovascular responses to static muscle contraction associated with dynamic changes in glutamate and GABA release within the RVLM and CVLM.     

Cholinergic inputs to rostral ventrolateral medulla pressor neurons from hypothalamus

The rostral ventrolateral medulla (RVLM) has cholinergic mechanisms responsible for pressor responses. Stimulation of the hypothalamic paraventricular nucleus (PVN) causes an increase of arterial pressure via activation of neurons in the RVLM. In this study, we examined whether PVN stimulation causes a pressor response via activation of cholinergic mechanisms in the RVLM. Male Wistar rats were used and they were anesthetized, paralyzed and artificially ventilated. Electrical stimulation of the PVN produced a pressor response. Microinjection of the muscarinic receptor antagonist scopolamine and the cholinesterase inhibitor physostigmine into the RVLM inhibited and potentiated, respectively, the pressor response induced by PVN stimulation. PVN stimulation also increased the firing rate of RVLM barosensitive neurons and the increase in the firing rate was inhibited and potentiated by scopolamine and physostigmine, respectively, iontophoretically applied on neurons. Microinjection of L-glutamate into the PVN produced a release of ACh in the RVLM. The inhibitory amino acid gamma-aminobutyric acid injected into the lateral parabrachial nucleus (LPBN) inhibited the pressor response induced by PVN stimulation. These results suggest that PVN stimulation causes an increase in arterial pressure via activation of cholinergic inputs in the RVLM. It appears that the pressor response is mediated, at least in part, via cholinergic inputs from the LPBN.     

Simultaneous glutamate and γ-aminobutyric acid release within ventrolateral medulla during skeletal muscle contraction in intact and barodenervated rats

The purpose of this study was to determine if baroreflex modulates cardiovascular responses and neurotransmitter release within rostral (RVLM) and caudal (CVLM) ventrolateral medulla during static contraction of skeletal muscle using anesthetized rats. We evoked cardiovascular responses by a static muscle contraction and measured simultaneous release of glutamate and γ-aminobutyric acid (GABA) in both the RVLM and CVLM using microdialysis probes, two inserted bilaterally into the RVLM and two into the CVLM. In intact anesthetized rats, a muscle contraction increased release of glutamate concomitantly in both the RVLM and CVLM along with significant increases in heart rate and arterial blood pressure. In contrast, concentrations of GABA increased within the RVLM, but decreased significantly within the CVLM during the pressor response. These changes were due to contraction-evoked activation of muscle afferents since tibial nerve stimulation following muscle paralysis failed to evoke glutamate, GABA, or any cardiovascular changes. On the other hand, static muscle contractions in baroreceptor denervated rats augmented the increases in heart rate and blood pressure. Furthermore, muscle contraction significantly enhanced the release of glutamate in the RVLM but attenuated its release in the CVLM. In addition, concentrations of GABA within the RVLM were attenuated following a muscle contraction in denervated rats without any changes in GABA within the CVLM. These results demonstrate that the baroreceptors influence cardiovascular responses to static muscle contraction associated with dynamic changes in glutamate and GABA release within the RVLM and CVLM.     

Central Amino Acids Mediate Cardiovascular Response to Angiotensin II in the Rat

To elucidate the role of the rostral ventrolateral medulla (RVLM) in cardiovascular control through the release of central amino acid neurotransmitters, experiments were performed in Sprague–Dawley (normotensive) rats and spontaneously hypertensive rats (SHR) anesthetized with urethane by using microdialysis sampling from the RVLM for determination of amino acid neurotransmitters. The baseline release of the excitatory amino acid neurotransmitter, glutamate (GLU) from the RVLM in SHR was higher and those of the inhibitory amino acid neurotransmitters, glycine (GLY), taurine (TAU), and γ-aminobutyric acid (GABA), were lower than in normotensive rats. Microinjection of angiotensin II (ANG II) into the RVLM caused a dose-dependent increase in mean arterial pressure (MAP) and heart rate (HR), accompanied by increased release of GLU in the RVLM. In contrast, microinjection of the ANG II type 1 receptor (AT₁) antagonist CV 11974 into the RVLM reduced MAP and HR, accompanied by increased release of GLY, TAU and GABA. These changes in MAP and HR after administration of ANG II or AT₁ antagonist were partially blocked by the use of the corresponding antagonist of each amino acid neurotransmitter. Furthermore, these effects were more prominently seen in SHR than in normotensive rats. These results suggest that the release of amino acid neurotransmitters mediate the cardiovascular effects of the angiotensin system in the RVLM, which may be involved in the generation of hypertension in SHR.     

Cardiovascular responses and neurotransmitter changes following blockade of nNOS within the ventrolateral medulla during static muscle contraction

Nitric oxide (NO) is synthesized from L-arginine through the activity of the synthetic enzyme, NO synthase (NOS). Previous studies have demonstrated the roles of the three isoforms of NOS, namely endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS) in cardiovascular regulation. However, no investigation has been done to study their individual role in modulating cardiovascular responses during static skeletal muscle contraction. In this study, we determined the effects of microdialyzing a specific nNOS antagonist into the rostral (RVLM) and caudal ventrolateral medulla (CVLM) on cardiovascular responses and glutamatergic/GABAergic neurotransmission during the exercise pressor reflex using rats. We hypothesized that the NO modulation of the exercise pressor reflex was largely influenced by specific nNOS activity within the ventrolateral medulla. Bilateral microdialysis of a selective nNOS antagonist, 1-(2-trifluoromethylphenyl)-imidazole (1.0 microM), for 30 or 60 min into the RVLM potentiated cardiovascular responses and glutamate release during a static muscle contraction. Levels of GABA within the RVLM were decreased. The cardiovascular responses and neurochemical changes to muscle contraction recovered following discontinuation of the drug. In contrast, bilateral application of the nNOS antagonist into CVLM attenuated cardiovascular responses and glutamate release during a static muscle contraction, but augmented GABA release. These results demonstrate that nNOS in the ventrolateral medulla plays an important role in modulating glutamatergic/GABAergic neurotransmission that regulates the exercise pressor reflex, and contributes to the sympathoexcitatory and sympathoinhibitory actions of NO within the RVLM and CVLM, respectively.     

大鼠头端延髓腹外侧区神经元对电刺激中脑导水管周围灰质背侧部及腹外侧部的反应（英文）

观察了大鼠延髓头端腹外侧区（rostralventrolateralmedulla，RVLM）神经元电活动对电刺激中脑导水管周围灰质背侧部及腹外侧部（dorsalandventrolateralperiaqueductalgraymatter，dPAG和vPAG）的反应。在139个神经元中,有92个被刺激dPAG兴奋；125个神经元中，有72个被刺激vPAG抑制。相当数量的神经元接受dPAG和vPAG的汇聚影响。刺激vPAG可减弱刺激dPAG在RVLM引起的兴奋反应。在检测的36个神经元中，有24个因具有压力敏感性并投射至脊髓而被认为是心血管神经元。这些结果与RVLM的心血管活动整合功能有关。     

Origin of tonic GABAergic inputs to vasopressor neurons in the subretrofacial nucleus of the rabbit

The aims of this study were to determine (1) whether the vasomotor effects reflexly elicited by baroreceptor stimulation are dependent upon gamma-aminobutyric acid (GABA) receptors in the subretrofacial (SRF) nucleus in the rostral ventrolateral medulla; (2) the extent to which inputs other than those arising from peripheral baroreceptors, or transmitted via the nucleus tractus solitarius (NTS), contribute to the tonic GABAergic inhibition of SRF vasopressor cells. Following bilateral injection of a mixture of the GABA antagonist bicuculline methiodide (500 pmol) and GABA agonist muscimol (500 pmol) into the SRF nucleus, the sympathoinhibitory response normally evoked by a rise in arterial pressure (induced by inflating an aortic cuff) was abolished in 4 out of 8 rabbits and reduced in the remainder. For the whole group, the mean reduction in this response was 71%. In other experiments, the pressor response produced by injection of bicuculline methiodide into the SRF nucleus was still present after (1) destruction of the intermediate portion of the NTS, and (2) complete removal of the brain rostral to the pons. We conclude that (1) an inhibitory GABAergic input into the SRF nucleus is an important component of the central pathways mediating baroreceptor inhibition of sympathetic vasomotor tone; (2) the SRF nucleus also receives tonic GABAergic inputs that are intrinsic to the lower brainstem and are independent of baroreceptor or other cardiovascular inputs relayed by the NTS.     

Neurons in the caudal ventrolateral medulla mediate the somato-sympathetic inhibitory reflex response via GABA receptors in the rostral ventrolateral medulla.

In urethane-anesthetized rabbits, stimulation of the sural nerve, consisting of cutaneous afferents (A-fibers), evoked reflex responses consisting of an early small excitatory component followed by a prolonged inhibitory component in renal sympathetic nerve activity. Bilateral injections of GABA antagonist, bicuculline (4 nmol/site), into the rostral ventrolateral medulla (RVLM), where sympatho-excitatory reticulospinal neurons are located, attenuated the inhibitory component in a dose-dependent manner as well as the inhibition evoked by stimulation of the aortic nerve A-fibers (baroreceptor afferents). Bilateral injections of a neurotoxic agent, kainic acid (4 nmol/site, 3 sites/side), into the caudal ventrolateral medulla (CVLM), where sympatho-inhibitory neurons with axonal projection to the RVLM are located, diminished these sympatho-inhibitory responses. Therefore it is concluded that the sympatho-inhibition evoked by activation of somatic afferents was mediated by neurons in the CVLM and by GABA receptors in the RVLM, as was the sympatho-inhibition associated with the arterial baroreceptor reflex. Bilateral injections of kynurenic acid (4 nmol/site, 3 sites/side) into the CVLM did not affect the somato-sympathetic reflex response, but diminished the sympatho-inhibition produced by activation of the baroreceptor afferents. Sympatho-inhibitory neurons in the CVLM were activated by glutamate when baroreceptor afferents were activated, but another excitatory transmitter may participate in the somato-sympathetic reflex in the CVLM.     

RVLM glycine receptors mediate GABAA and GABAB)independent sympathoinhibition from CVLM in rats

The caudal ventrolateral medulla (CVLM) provides tonic inhibitory and also excitatory inputs to the rostral ventrolateral medulla (RVLM). These experiments evaluated the role of RVLM gamma-amino butyric acid (GABA) receptor subtypes and glycine receptors in mediating CVLM sympathoinhibition. In Inactin anesthetized female rats, the CVLM and RVLM were functionally defined by pressor and depressor responses to microinjected GABA (500 pmol, 50 nl). Although reduced, pressor and sympathoexcitatory responses due to inhibition of the CVLM with GABA persisted following ipsilateral RVLM GABA(A) receptor blockade (bicuculline, BIC, 400 pmol, 100 nl; n=12) in rats with contralateral nucleus tractus solitarius (NTS) lesion. In the presence of either ipsilateral (+contralateral NTS lesion; n=8) or bilateral (n=6) GABA(A) and GABA(B) receptor blockade of the RVLM (400 pmol BIC+400 pmol CGP35348, 100 nl), inhibition of the CVLM still increased MAP and renal sympathetic nerve activity (RSNA). Thus neither GABA(B) receptors nor a contralateral CVLM to RVLM GABAergic pathway explains residual responses to CVLM blockade. The addition of strychnine (300 pmol, 100 nl) to the RVLM eliminated responses to CVLM inhibition, suggesting that a GABA(A) and GABA(B) independent sympathoinhibitory influence from CVLM to RVLM is mediated by glycine receptors. Decreases in MAP and RSNA due to activation of the CVLM with glutamate (500 pmol, 50 nl) were reversed to increases in the presence of RVLM GABA(A) receptor blockade (n=7). Thus, a sympathoexcitatory pathway from the CVLM can be activated in the presence of RVLM GABA receptor blockade, but sympathoinhibitory influences from the CVLM predominate.     

The rostral parvicellular reticular formation neurons mediate lingual nerve input to the rostral ventrolateral medulla

In rats that had been anesthetized by urethane-chloralose, we investigated whether neurons in the rostral part of the parvicellular reticular formation (rRFp) mediate lingual nerve input to the rostral ventrolateral medulla (RVLM), which is involved in somato-visceral sensory integration and in controlling the cardiovascular system. We determined the effect of the lingual nerve stimulation on activity of the rRFp neurons that were activated antidromically by stimulation of the RVLM. Stimulation of the lingual trigeminal afferent gave rise to excitatory effects (10/26, 39%), inhibitory effects (6/26, 22%) and no effect (10/26, 39%) on the RVLM-projecting rRFp neurons. About two-thirds of RVLM-projecting rRFp neurons exhibited spontaneous activity; the remaining one-third did not. A half (13/26) of RVLM-projecting rRFp neurons exhibited a pulse-related activity, suggesting that they receive a variety of peripheral and CNS inputs involved in cardiovascular function. We conclude that the lingual trigeminal input exerts excitatory and/or inhibitory effects on a majority (61%) of the RVLM-projecting rRFp neurons, and their neuronal activity may be involved in the cardiovascular responses accompanied by the defense reaction.     

Brain sources of inhibitory input to the rat rostral ventrolateral medulla

The rostral ventrolateral medulla (RVLM) contains neurons critical for cardiovascular, respiratory, metabolic, and motor control. The activity of these neurons is controlled by inputs from multiple identified brain regions; however, the neurochemistry of these inputs is largely unknown. Gamma‐aminobutyric acid (GABA) and enkephalin tonically inhibit neurons within the RVLM. The aim of this study was to identify all brain regions that provide GABAergic or enkephalinergic input to the rat RVLM. Neurons immunoreactive for cholera toxin B (CTB‐ir), retrogradely transported from the RVLM, were assessed for expression of glutamic acid decarboxylase (GAD67) or preproenkephalin (PPE) mRNA using in situ hybridization. GAD67 mRNA was expressed in CTB‐ir neurons in the following regions: the nucleus of the solitary tract (NTS, 6% of CTB‐ir neurons), area postrema (AP, 8%), caudal ventrolateral medulla (17%), midline raphe (40%), ventrolateral periaqueductal gray (VLPAG, 15%), lateral hypothalamic area (LHA, 25%), central nucleus of the amygdala (CeA, 77%), sublenticular extended amygdala (SLEA, 86%), interstitial nucleus of the posterior limb of the anterior commissure (IPAC, 56%), bed nucleus of the stria terminals (BNST, 59%), and medial preoptic area (MPA, 53%). PPE mRNA was expressed in CTB‐ir neurons in the following regions: the NTS (14% of CTB‐ir neurons), midline raphe (26%), LHA (22%), zona incerta (ZI, 15%), CeA (5%), paraventricular nucleus (PVN, 13%), SLEA (66%), and MPA (26%). Thus, limited brain regions contribute GABAergic and/or enkephalinergic input to the RVLM. Multiple neurochemically distinct pathways originate from these brain regions projecting to the RVLM. J. Comp. Neurol. 521:213–232, 2013. © 2012 Wiley Periodicals, Inc.     

Cardiovascular responses to muscle contraction following microdialysis of nitric oxide precursor into ventrolateral medulla

We determined the effects of administering L-arginine, a precursor for the synthesis of nitric oxide, and L-NMMA (NG-monomethyl-L-arginine), a nitric oxide synthase blocker, into the rostral (RVLM) and caudal (CVLM) ventrolateral medulla on cardiovascular responses elicited during static contraction of the triceps surae muscle. Two microdialysis probes were inserted bilaterally into the RVLM or CVLM of anesthetized Sprague-Dawley rats using stereotaxic guides. For RVLM experiments, static muscle contraction evoked by stimulation of the tibial nerve increased mean arterial pressure (MAP) and heart rate (HR) by 29+/-3 mmHg and 44+/-7 bpm, respectively (n=8). Microdialysis of L-arginine (1.0 microM) for 30 min attenuated the contraction-evoked increases in MAP and HR. After discontinuing L-arginine, L-NMMA (1.0 microM) was microdialyzed into the RVLM for an additional 30 min followed by a muscle contraction. This contraction augmented the pressor response (37+/-4 mmHg) and HR (61+/-11 bpm) with respect to control values. For CVLM experiments, muscle contraction increased MAP and HR by 23+/-3 mmHg and 25+/-5 bpm, respectively (n=9). Microdialysis of L-arginine (1.0 microM) for 30 min potentiated the contraction-evoked increases in MAP and HR. Subsequent administration of L-NMMA (1.0 microM) into the CVLM for an additional 30 min blocked the augmented MAP and HR responses. Developed tensions did not alter during contractions throughout both RVLM and CVLM protocols. These results suggest that nitric oxide, within the RVLM and CVLM, plays an opposing role in modulating cardiovascular responses during static muscle contraction.     

Responses of single units in the midline medulla to stimulation of the rostral ventrolateral medulla.

Single units in the midline medulla were characterized as sympathoexcitatory (SE), sympathoinhibitory (SI) or serotonin (5-HT) neurons. Post-stimulatory changes in the firing patterns of sympathoexcitatory, sympathoinhibitory and 5-HT units were observed during single shock stimulation of the pressor area of the rostral ventrolateral medulla (RVLM). Excitation, inhibition, or no change in cell firing patterns were observed for each cell type, but each cell showed only one type of response to stimulation. No midline neurons were antidromically activated by stimulation of the rostral ventrolateral medulla. These results are discussed in relation to neuronal pathways between the RVLM and the midline medulla involved in the generation of sympathetic activity.     

Activation of noradrenergic mechanism attenuates glutamate-induced vasopressor responses in the pons and medulla of cats in vivo.

1. Using anesthetized cats, the authors examined the noradrenergic modulation of the glutamate induced pressor and depressor responses in various brainstem areas, including pontine gigantocellular tegmental field (FTG), dorsomedial medulla (DM), rostral ventrolateral medulla (RVLM), and caudal ventrolateral medulla (CVLM). 2. Unilateral microinjection of L-glutamate (Glu, 3 nmol in 30 nL saline) into FTG, DM and RVLM produced an increase in systemic arterial pressure (SAP) and a decrease in heart rate (HR), while into CVLM produced decreases of SAP and HR. 3. Application of norepinephrine (NE) into the pressor areas (0.05 to 5 nmol) did not alter the resting SAP and HR, but significantly attenuated the Glu-induced pressor response with an order of potency: FTG > DM > RVLM. In the depressor CVLM, NE alone produced a dose-dependent decrease of resting SAP and HR, but did not affect the Glu-induced depressor responses. 4. The involvement of different adrenoceptor subtypes was further investigated by application of selective adrenoceptor agonists including phenylephrine (alpha1), clonidine (alpha2), and isoproterenol (beta). Responses to these agonists are similar to those elicited by NE, except that only alpha-adrenoceptor agonists could antagonize the Glu-induced pressor responses of the RVLM. 5. Our observations indicate that NE not only inhibits the pressor mechanisms in various brainstem areas but also elicits a direct depressor response in CVLM. These findings also suggest that NE acts more likely a neurotransmitter, rather than a modulator, in the CVLM.     

Hypothalamic projections to cardiovascular centers of the medulla

The purpose of this project was to identify hypothalamic neurons having projections to two cardiovascular centers of the medulla, the rostral ventrolateral medulla (RVLM; a vasopressor region) and the nucleus of the solitary tract (NTS; a vasodepressor region). To accomplish this, fluorescent tracers (fast blue and diamidino yellow) were injected into NTS and RVLM, after each site had been physiologically identified in rats. In each case, one of the tracers was injected into the RVLM and another was injected into the NTS. Labelled neurons were subsequently observed along the entire rostral-caudal extent of the hypothalamus, where they were found in nuclei having known cardiovascular functions. Although the two groups of hypothalamomedullary neurons were largely overlapped in their distributions, less than 0.1% of the neurons were double labelled. In addition to this overlapping distribution of neurons, there were some areas within the hypothalamus where the two groups of hypothalamomedullary neurons were somewhat segregated. This clustering pattern was observed in the posterolateral hypothalamus (PLH) and, to a much lesser degree, in the paraventricular nucleus (PVN). Within the PLH, lying medial to the subthalamic nucleus, virtually all the labelled neurons projected exclusively to the NTS. Within the PVN, neurons projecting to the NTS were more numerous ventrally, whereas neurons projecting to the RVLM were more evenly dispersed within the PVN. In addition to hypothalamic labeling, clusters of labelled neurons were also observed in the zona incerta and the interstitial nucleus of the stria terminalis. Within the zona incerta, almost all the labelled neurons projected to the RVLM. Within the interstitial nucleus of the stria terminalis, neurons projecting to NTS were much more abundant in the dorsal portion of this nucleus; whereas, neurons projecting to the RVLM were more abundant ventrally. The findings of this study provide additional support to the notion that hypothalamic influences upon cardiovascular functions are in part mediated through hypothalamomedullary projections.