n-Chin Wu

Nitric oxide reduces blood pressure in the nucleus tractus solitarius: a real time electrochemical study

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 nNOS/cGMP signal transducing system is involved in the cardiovascular responses induced by activation of NMDA receptors in the rostral ventrolateral medulla of cats

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.

Propofol inhibits medullary pressor mechanisms in cats

PurposePropofol may cause hypotension and the mechanism is complex. The present study was designed to determine the direct actions of propofol in medulla of cats.MethodsMean 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.ResultsPropofol 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 < 0.01) or in RVLM (56 ± 4 % vs 18 ± 2 %, n = 9,P < 0.01). In CVLM, propofol slightly but not significantly increased the depressor responses elicited by Glu (−27 ± 2 %vs ∼-33 ± 3 %. n = 5,P > 0.05).ConclusionOur results show that propofol principally inhibits the vasomotor mechanism in the dorsomedial and ventrolateral medulla to effect its hypotensive actions.RésuméObjectifLe propofol produit de l’hypotension par un mécanisme complexe. Cette étude avait pour objectif de délimiter sur le bulbe du chat l’activité directe du propofol.MéthodesLa pression artérielle systémique moyenne (PASM), la fréquence cardiaque (FC) et la contractilité cardiaque (dp/dt) ont été comparées avant et après l’injection de propofol dans la veine fémorale (2, 3 et 4 mg · kg−1), l’artère vertébrale (1 mg · kg−1) et le ventricule cérébral latéral (0, 5 mg · kg−1) chez six chats anesthésiés. Pour étudier les effets bulbaires directs du propofol, les zones vasopressives dorsomédiane (DM) et ventrolatérale rostrale (BVLR) bulbaires, ou la zone vasodépressive ventrolatérale caudale (BVLC) bulbaire ont d’abord été identifiées par stimulation électrique et confirmées par micro-injection sous pression de glutamate (Glu 0.25M, 30 ml) à l’aide d’une micropipette à plusieurs banllets chez 28 chats. Une heure plus tard, du propofol (0, 001%, 50 nl) était injecté au même site. Lélectrostimulation et Glu étaient appliqués encore une fois pour comparer les changements de PAS. le FC et de dp/dt avec ceux du contrôle.RésultatsDépendaminent de la dose, le propofol diminue PAS, FC etdp/dt. En pourcentage, l’augmentation de PASM induite par Glu était réduite par le propofol dans DM 159 ± 3 %va 13 ± 2 %. n= 11,P < 0, 01) ou dans BLVR (56 ± 4 %vs 18± 2%, n = 9, P < 0.01). Dans BLVM, le propofol a augmenté légèrement mais non significativement les réponses vasodépressives induites par Glu (−27 ± 2 % vs −33 ± 3 %. n = 5,P < 0, 05).ConclusionNos résultats montrent que l’action hypotensive du propofol est causée par l’inhibition du mécanisme vasomoteur au niveau des zones bulbaires dorsomédiane et ventrolatérale.

Glycine increases arterial pressure and augments NMDA-induced pressor responses in the dorsomedial and ventrolateral medulla of cats

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 alpha-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.

Nitric oxide release in the nucleus tractus solitarius during and after bilateral common carotid artery occlusion.

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).

Glycine produced pressor responses when microinjected in the pressor areas of pons and medulla in cats

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 rostral 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.

Modulation of Propofol on the Effects of Blood Pressure and Firing Activity of Related Neurons in the Medulla

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.