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Many studies have demonstrated that the ventrolateral medulla (VLM) plays an important role in the maintenance of systemic arterial pressure (SAP) and vascular tone. The VLM is divided into rostral (RVLM) and caudal (CVLM) portions which play opposing roles in regulating cardiovascular functions. The purposes of this study are to explore the relationship of fibers projecting between the RVLM and CVLM, and to investigate the effect of propofol (PPF, 2 mg/kg), an anesthetic agent, on modulating their neuronal firing rate (NFR). Forty-four adult cats were anaesthetized intraperitoneally with urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). The femoral artery was cannulated to allow monitoring of SAP and heart rate (HR). The femoral vein was cannulated for intravenous drug administration. Microinjection of glutamate (Glu, 3.0 nmol/30 nl), kynurenic acid (Kyn, 3.0 nmol/30 nl), gamma-aminobutyric acid (GABA, 4.0 nmol/30 nl), or bicuculline (Bicu, 4.0 nmol/30 nl) into the RVLM produced SAP increases or decreases, but did not significantly change the NFR in the CVLM. This occurred even after intravenous administration of PPF. This shows that there are few fiber projections from the RVLM to the CVLM. Conversely, microinjection of Glu, Kyn, GABA or Bicu into the CVLM produced SAP changes, and the NFR in the RVLM was significantly changed. These changes were more significant after intravenous administration of PPF. These results show that there are more fibers projecting from the CVLM to the RVLM and fewer fibers projecting from the RVLM to the CVLM to affect the SAP and its NFR.

Nitric oxide (NO) is synthesized from L-arginine by NO synthase (NOS). NO stimulates the soluble form of guanylyl cyclase (sGC) and induces accumulation of cyclic guanosine monophosphate (cGMP). The purpose of this study was to examine whether the cardiovascular responses induced by N-methyl-D-aspartate (NMDA) in the rostral ventrolateral medulla (RVLM) depend on the actions of NOS and sGC. In anesthetized cats, the extracellular NO level was measured by in vivo voltammetry using a nafion/porphyrine/o-phenylenediamine-coated carbon-fiber electrode. Microinjection of NMDA into the RVLM produced hypertension and bradycardia associated with NO formation. These NMDA-induced responses were attenuated by prior injections of 7-nitroindazole, a neuronal NO synthase (nNOS) inhibitor, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a sGC inhibitor. These findings suggest that NO is involved in the NMDA-induced cardiovascular responses in the RVLM.

In the pretentorial periaqueductal grey (PAG), the region producing pressor responses, vocalization and other somatic and visceral signs (VPR) of the defence reaction and another region producing pressor responses (PR) were localized by electrical stimulation in adult cats, anesthetized with intraperitoneal chloralose (40 mg/kg) and urethane (400 mg/kg). The pressor responses included increases of systemic arterial pressure (SAP) and heart rate, increases of blood flow in the common carotid and femoral arteries and a decrease of blood flow in the superior mesenteric artery. The VPR was found in a relatively restricted region of the dorsolateral PAG, while PR was found scattered within the dorsal and ventral portions of the lateral PAG. The increase of SAP and the changes of blood flow in the sampled arteries were slightly greater during VPR than PR stimulation. Mild vocalization with a slight increase of SAP but marked increases of carotid and femoral blood flow (vasodilation) could be induced by microinjection of N-methyl d -aspartate (0.2 M, 200 nl) into the VPR and the blood flow increase, particularly that of the femoral artery, was greatly attenuated by atropine (1 mg/kg, i.v.). In order to ascertain the contribution of the medullary pressor areas to the VPR- and PR-induced responses, extensive lesions were made in the dorsomedial (DM) or vetrolateral medulla (VLM) by microinjections of kainic acid (KA, 0.024 M) in 27 of the 42 cats. The resting SAP and blood flow of the three arteries were reduced by lesioning of the VLM more than that of the DM. Responses of SAP and blood flow from activation of the PR and VPR, particularly the latter, were affected more after DM compared to VLM lesioning. These data suggest that, while the pretentorial PAG constitutes the `defence area', vocalization is confined exclusively to its dorsolateral region and that both the VLM and DM contribute to the cardiovascular components of defence reactions. The DM appears to have a greater contribution compared to the VLM.

The aim of this study was to investigate the effects of the cannabinoid receptor agonist, WIN55212-2, and the cannabinoid receptor antagonist, SR141716A, on dopamine (DA) release evoked by KC1 (120 mM) microinjected into the striatum. The cannabinoid agonist WIN55212-2 (1 and 5 mg/kg, i.p.) dose-dependently attenuated DA release in the striatum, whereas the cannabinoid receptor antagonist SR141716A (3 mg/kg, i.p.) produced the opposite effect. SR141716A (3 mg/kg, i.p.) blocked the effects on DA release by WIN55212-2 (5 mg/kg, i.p.). Vehicle alone did not change DA release. These results suggest that cannabinoids modulate DA release in the striatum.

The effect of propofol on neuronal activity in the rostral ventrolateral medulla (RVLM) is not well established. Therefore, we performed extracellular recording on neurons of the RVLM to investigate neuronal activity before and after administration of intravenous propofol. The mean systemic arterial pressure (MSAP), heart rate and integrated neuronal firing rate (INFR) in the RVLM were continuously recorded in anesthetized cats before and after intravenous injection of 2 mg/kg propofol or supplemental injections of 1, 2 and 4 mg/kg propofol that were given respectively. Additionally, we compared the MSAP, heart rate (HR), and INFR in the RVLM following intravenous injection of 2 mg/kg propofol or 12.5 microg/kg nitroprusside. Neuronal firing was dose-dependently and reversibly inhibited after the supplemental doses of 1, 2 and 4 mg/kg propofol. The control INFR was 14.2 +/- 9.9 Hz, and this decreased to 12.1 +/- 9.4 Hz after the first dose of propofol (P = 0.085 vs. control), and further decreased to 9.3 +/- 7.7 Hz (P = 0.001 vs. control) and 7.5 +/- 7.7 Hz (P0.001 vs. control) after the second and third doses of propofol, respectively. Besides, SAP and HR were dose-dependently decreased by propofol as well. However, the effects of propofol and nitroprusside on neuronal activity in the RVLM differed. Propofol inhibited neuronal firing, whereas nitroprusside activated neuronal firing. In conclusion, propofol may dose-dependently inhibit spontaneous neuronal activity and the baroreflex in the RVLM.

We examined the effects of serotonin (5-HT) on cardiovascular responses and blood flows in the right common carotid artery (RCCA), superior mesenteric artery (SMA) and right femoral artery (RFA), stimulated by glutamate (Glu) in the dorsomedial medulla (DM), rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM). Microinjection of Glu into the DM produced increases in systemic arterial pressure (SAP) and flows in the RCCA and RFA, and decrease in flow in the SMA. Microinjection of Glu into the RVLM produced increases in SAP and decreases in flows in the RCCA, SMA and RFA. Prior microinjections of 5-HT into the same sites attenuated all the Glu-induced responses. Microinjection of Glu into the CVLM produced decreases in SAP and flows in the RCCA, SMA and RFA. These decreases were potentiated by prior injection of 5-HT. These findings suggest that 5-HT modulates the cardiovascular and blood flow responses induced by Glu in the medulla.

The rostral ventrolateral medulla (RVLM) plays an important role in the integration of cardiovascular functions. We examined the effect of asphyxia on cardiovascular responses, on sympathetic vertebral nerve activity (VNA) and nitric oxide (NO) formation in the RVLM, on hemodynamics, and on plasma concentrations of catecholamines, blood gas partial pressures and carbohydrate metabolites. Using 16 anesthetized cats we found that the systemic arterial pressure (SAP), VNA, NO formation and the release of plasma catecholamine components of norepinephrine and epinephrine were increased during asphyxia. The onset of NO production was significantly earlier than that of SAP and VNA. The venous partial pressure of O2 decreased, while the partial pressure of CO2 increased. Furthermore, metabolism of glucose and lactate increased, as did the blood concentrations of white and red blood cells, hemoglobin and platelets. Thus, asphyxia increased SAP, VNA and NO formation. It increased the plasma catecholamines, blood gases, carbohydrate metabolites and blood cells.

Using in vivo voltammetry to directly measure extracellular nitric oxide (NO) levels, our previous studies suggested that the neuronal NO synthase (nNOS) and cyclic guanosine monophosphate (cGMP) signal transducing systems are involved in the cardiovascular responses elicited by activation of N-methyl-D-aspartate (NMDA) receptors in the rostral ventrolateral medulla. In this study, we examined if the depressor responses elicited by activation of NMDA receptors in the caudal ventrolateral medulla (CVLM) also depend on the actions of nNOS and soluble guanylyl cyclase. In anesthetized cats, microinjection of NMDA into the CVLM produced hypotension and bradycardia associated with NO formation. These NMDA-induced responses were attenuated by prior injections of 2-amino-5-phosphonopentanoate (a NMDA receptor competitive antagonist), 7-nitroindazole (a nNOS inhibitor) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase). These findings suggest that NO is also involved in the NMDA-induced depressor responses of the CVLM.

SUMMARY 1. The purpose of the present study was to investigate the effect of bilateral common carotid artery occlusion (BCCAO) on cardiovascular responses and nitric oxide (NO) formation in the nucleus tractus solitarius (NTS). 2. Twenty-three adult cats were anaesthetized intraperitoneally with urethane (400 mg/kg) and α-chloralose (40 mg/kg). The femoral artery was cannulated to allow monitoring of systemic arterial pressure (SAP) and heart rate (HR). The femoral vein was cannulated for intravenous drug administration. 3. Extracellular NO levels in the NTS were measured by in vivo voltammetry using an NO microsensor combined with a microcomputer-controlled apparatus. 4. Microinjection of l-arginine (30 nmol) into the NTS produced hypotension and NO release. This effect of l-arginine was not changed by 2 min of BCCAO. 5. Bilateral common carotid artery occlusion produced increases in SAP and NO levels. These effects were more apparent in vagotomized than in intact animals. 6. The onset latency of BCCAO-induced changes in SAP levels (8.4 ± 2.5 s) was longer than that for changes in NO (4.7 ± 1.7 s). 7. Bilateral common carotid artery occlusion induced hypertension and NO release in the NTS of intact and vagotomized animals. These cardiovascular and NO responses to BCCAO were significantly attenuated by NG-nitro-l-arginine methyl ester (10 mg/kg, i.v.) and MK-801 (2.5 mg/kg, i.v.). These data suggest that NO synthase and activation of N-methyl-d-aspartate receptors are involved in the cardiovascular and NO responses to BCCAO.

Propofol is a potent intravenous anesthetic. The action of propofol on the medullary depressor area, the caudal ventrolateral medulla (CVLM), has not been well established. We therefore performed extracellular recordings to study the neuronal activity of the CVLM in cats before and after intravenous propofol administration, to investigate its influence on neuronal firings.Experiments were performed on 31 cats anaesthetized with a mixture of alpha-chloralose and urethane administered intraperitoneally. Mean systemic arterial pressure, heart rate, and the neuronal firing (NF) rate were continuously recorded before and after intravenous injection of a single dose of 2 mg x kg(-1) propofol or separate supplemental doses of 1, 2, and 4 mg x kg(-1) propofol until those parameters had returned to the premedication level.Propofol dose-dependently and reversibly inhibited the NF rate after the supplemental doses of 1, 2, and 4 mg x kg(-1) propofol. The control NF rate of 17.9 +/- 8.6 Hz was depressed to 15.8 +/- 8.5 Hz after the first dose of propofol (p0.05 vs. the control), and was further depressed to 12.8 +/- 8.3 Hz (p0.05 vs. the control) and 10.0 +/- 7.9 Hz (p0.05 vs. the control) after the second and the third doses of propofol, respectively.The dose-dependent inhibition of the spontaneous neuronal firing rate is the main pharmacological action of propofol in the caudal ventrolateral medulla of cats.

Increasing evidence has demonstrated that nitric oxide (NO) is involved in central cardiovascular regulation. In this study, we directly measured extracellular NO levels, in real-time, in the nucleus tractus solitarius (NTS) of anesthetized cats using Nafion/Porphyrine/o-Phenylenediamine-coated NO sensors. We found that local application of L-arginine (L-Arg) induced NO overflow in NTS and hypotension. These responses were potentiated in the vagotomized animals. Pretreatment with NO synthase (NOS)/guanylate cyclase inhibitor methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or NO scavenger hemoglobin attenuated L-Arg-induced hypotension, suggesting that exogenous supplement of NO suppressed cardiac functions through the NOS/cyclic guanosine monophosphate mechanism. The role of endogenous NO was examined after local application of N(G)-nitro-L-arginine methyl ester (L-NAME). We found that L-NAME suppressed endogenous NO levels in NTS and elicited hypertension and tachycardia. Taken together, our data suggest that NO is tonically released in the NTS to inhibit blood pressure.

The present study is designed to determine and characterize two neurobiological events. Firstly, we investigated whether increases of systemic arterial pressure (SAP) and sympathetic vertebral nerve activity (VNA) produced by microinjection of glycine (Gly) in the dorsomedial (DM) or rostral ventrolateral medulla (RVLM) are mediated by pressor neurons in DM or RVLM. Secondly, we assessed whether simultaneous microinjections of Gly and N -methyl- d -aspartate (NMDA) in DM or RVLM potentiate the NMDA-pressor effects. Changes in SAP and VNA were recorded in 33 cats under α -chloralose and urethane anesthesia. Microinjection of sodium glutamate (Glu, 0.25 M, 30 nl) or Gly (1.0 M, 30 nl) into the DM or RVLM increased SAP and VNA in similar magnitude. Latencies of changes in SAP and VNA induced by Gly, however, were longer (3 s) than those induced by Glu. Prior microinjection of the following antagonists blocked the Gly-induced pressor responses: 2-amino-5-phosphonopentanoate (AP-5, 25 mM, 30 nl), a specific NMDA receptor antagonist; or glutamate diethyl ester (GDEE, 0.5 M, 30 nl), a quisqualate receptor antagonist; or kynurenic acid (KYN, 10 mM, 30 nl), a broad spectrum competitive Glu antagonist. Prior treatment with strychnine (3 mM, 30 nl), a specific Gly antagonist, also blocked the Gly-induced pressor responses. Since Gly is believed to be an inhibitory neurotransmitter, these data suggest that Gly may produce pressor actions via an inhibition on specific inhibitory neurons synapsing with the pressor neurons. NMDA (0.1 M, 30 nl) and Gly (1.0 M, 30 nl) microinjected simultaneously in DM or RVLM produced a greater pressor action than NMDA alone. This potentiation was blocked by KYN, another known antagonist for such potentiation, but was only partially blocked by strychnine.

Propofol may cause hypotension and the mechanism is complex. The present study was designed to determine the direct actions of propofol in medulla of cats. Mean systemic arterial pressure (MSAP), heart rate (HR) and cardiac contractility (dp/dt) were compared before and after administration of propofol through the femoral vein (2, 3 or 4 mg · kg−1), vertebral artery (1 mg · kg−1) or the lateral cerebral ventnricle (0.5 mg · kg−1) in eight anaesthetized cats. To study the direct effect of propofol in medulla, pressor areas of the dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM), or the depressor area of the caudal ventrolateral medulla (CVLM) were first identified with electrical stimuli and then confirmed by pressure microinjection of glutamate (Glu, 0.25M, 30 nl) via a multibarrel-micropipette in 28 cats. One hour later, propofol (0.001%, 50 nl) was microinjected at the same site. Electrical stimulation and Glu were applied again to compare changes of SAR HR and dp/dt with that of the control. Propofol dose-dependently decreased SAR HR and cardiac contractility. The percent increase of MSAP induced by Glu were reduced by propofol in DM (59 ± 3 % vs 13 ± 2 %, n = 11.P 0.05). Our results show that propofol principally inhibits the vasomotor mechanism in the dorsomedial and ventrolateral medulla to effect its hypotensive actions. Nos resultats montrent que l’action hypotensive du propofol est causee par l’inhibition du mecanisme vasomoteur au niveau des zones bulbaires dorsomediane et ventrolaterale.

In 24 cats under chloralose/urethane anesthesia changes of systemic arterial pressure (SAP) and sympathetic vertebral nerve activities (VNA) were induced by microinjection of glycine (Gly, 1.0 M, 50 nl) into the pressor areas of the rostra] pons, i.e., locus coeruleus-parabrachial nucleus (LC-PBN), nucleus of gigantocellular tegmental field-lateral tegmental field (FTG-FTL), and dorsomedial (DM) and ventrolateral (VLM) medulla. The effects were compared with those induced by microinjection of sodium glutamate (Glu, 0.25 M, 50 nl) into the same sites. In about 60% of the injections Gly produced increases in SAP and VNA similar to that of Glu. The increase in SAP was greater in VLM, while the increase in VNA was more marked in DM. In the rest of microinjections Gly and Glu produced changes of SAP and VNA in different combinations. The latency of Gly-induced increases in SAP and VNA was 1 to 3 s longer than that induced by Glu. Our findings show that although Gly is classified as an inhibitory transmitter, it often produced excitation of the pressor neurons in the pons and medulla similar to that of Glu. Whether Gly acts through the same cardiovascular neurons that respond to Glu or through activation of different kinds of neurons remains to be elucidated.