Chok-Yung Chai

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.

Cardio-inhibitory mechanism in the gigantocellular reticular nucleus of the medulla oblongata

A cardio-inhibitory mechanism was localized in the ventral part of the medullary gigantocellular reticular nucleus (GRN) in chloralose--urethane anesthetized cats. Stimulation of this mechanism produced an average 58.9% reduction of the heart rate (calculated from 55 responsive points having more than 40% reduction) associated mostly with hypotension, or no change or occasionally a slight increase of the arterial blood pressure. Midcollicular decerebration did not affect this bradycardia. The bradycardia following GRN stimulation of either side by a pair of symmetrically placed electrodes was reduced slightly but equally by: (1) sectioning either side of the vagus nerve; (2) hemisection at a level 4 mm rostral of the obex on either side; or (3) partial destruction of the dorsal motor (DM) and solitary (SN) nuclei on either side. Additional section of the vagus nerve on the opposite side completely abolished the bradycardiac response. Besides, the GRN bradycardia was also slightly but equally attenuated by making a midline bisection in a length extending from 10 to 4 mm rostral of the obex. Additional section of the vagus nerve on either side abolished completely only the bradycardia following electrical stimulation of the GRN on the same side, while that following electrical stimulation of the GRN on the opposite side remained unaffected. On the other hand, the GRN bradycardia was not affected by simply making a caudal midline bisection in a length extending from 3 or 4 mm rostral to 2 mm caudal of the obex. The results suggest: (1) the ventral part of the GRN is a cardio-inhibitory mechanism independent of the higher center; (2) the efferent pathway descends both ipsilaterally and contralaterally and makes synaptic relay in the areas of DM and/or SN and finally exits via the vagus nerves; (3) the fibers decussate rostral to the level 4 mm rostral of the obex; and (4) both ipsilateral and contralateral descending fibers appeared to exert the same degree of suppressive influence in the heart rate.

Homocysteic acid elicits pressor responses from ventrolateral medulla and dorsomedial medulla

In rats and cats anesthetized with alpha-chloralose and urethane, the pressor response and its relative reactivity were studied following microinjection of dl-homocysteic acid (DLH, 2 nmol in 40 nl of saline) into the dorsomedial medulla (DM) or the ventrolateral medulla (VLM). DLH, which excites only cell bodies of neurons but not fibers of passage, consistently produced pressor responses in DM and VLM in both cats and rats. The pressor effects elicited from VLM were more pronounced than those from DM. In cats, the most active areas for DLH were found in the rostral and midmedulla; the pons and caudal medulla were less active. The pressor responses from DM and VLM were augmented following bilateral vagotomy, persisted after sectioning of the carotid sinus and aortic depressor nerves, and after cauterization of the carotid bodies with phenol. The response induced by DLH was more apparent from VLM than that from DM. These pressor effects were evoked directly by activation of neurons in these two regions, and were not necessarily related to any homocysteate blockade of baroreceptor and/or chemoreceptor reflexes. These results suggest that in the medulla there reside at least two discrete pressor areas, DM and VLM containing neuronal perikarya.

Involvement of Non-Nmda and Nmda Receptors in Glutamate-Induced Pressor or Depressor Responses of the Pons and Medulla

1. Fifty‐five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito‐neally with urethane (400 mg/kg) and a‐chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded.

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.

CHANGES IN INTRA‐ AND EXTRACRANIAL TISSUE BLOOD FLOW UPON STIMULATION OF A RETICULAR AREA DORSAL TO THE FACIAL NUCLEUS IN CATS

1. A small area in the dorsal part of the lateral tegmental field specifically responsible for the increase of blood flow in the common carotid artery (CCA) without accompanying change in the resting blood pressure was first identified in our laboratory. Since the area is located just dorsal to the facial nucleus, we named it the dorsal facial area (DFA; Kuo et al. 1987).

Role Of Nitric Oxide On Pressor Mechanisms Within The Dorsomedial And Rostral Ventrolateral Medulla In Anaesthetized Cats

1. The role of nitric oxide (NO) in central cardiovascular regulation and the correlation between NO and glutamate‐induced mechanisms is not clear. Microinjection of glutamate (3 nmol/ 30 nL) into dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM) increased arterial blood pressure (BP) and sympathetic vertebral nerve activity (VNA). Thus, in the present study, we examined the modulation by NO of glutamate‐induced pressor responses in the DM and RVLM of cats.

Castration May Not Affect the Penile Erection Ability In Terms of Peripheral Neurocavernous Mechanism in Dogs

The penile erection ability (PEA) was assessed in 27 dogs with intact orchids (Group I), seven dogs with bilateral orchidectomy for one month (Group II) and four dogs with bilateral orchidectomy for three months (Group III). PEA was indicated by the increase of the intracorporeal pressure (ICP) upon electrical stimulation of the cavernous nerves. PEA was significantly decreased in both orchidectomized groups. However, when reduction in the blood pressure was considered, the difference in PEA between Group I and the orchidectomized group was no longer significant. Before the orchidectomy, plasma testosterone level of 22 adult male dogs varied widely from 105 to 6302 pg./ml. At one or three months after the orchidectomy in 11 dogs, it decreased to a level below 100 pg./ml. There was no significant change in the body weight in the post orchidectomy period. These findings indicate that the castration and/or the resulting low plasma testosterone level does not directly affect PEA through the peripheral neural and cavernosal mechanism.

Striatal Dopamine Dynamics Are Altered Following an Intranigral Infusion of Iron in Adult Rats

In vivo electrochemical detection was employed to examine iron-induced oxidative injury on dopamine dynamics in the nigrostriatal system of urethane-anesthetized rats. Seven days after an intranigral infusion of iron, oxidative stress was confirmed by an elevated lipid peroxidation in lesioned substantia nigra (SN). Local application of potassium (K+) evoked dopamine releases from the dopamine-containing nerve terminals in the striatum. Both amplitude and rate of clearance (Tc) of evoked dopamine releases were lower in striatum with lesioned SN; however, the time course parameters of dopamine release in the lesioned group were not different from those of the intact group, indicating a reduction in dopamine clearance. Indeed, iron-induced oxidative stress attenuated the effect of nomifensine, a high-affinity dopamine uptake blocker, on dopamine clearance. In striatum with intact SN, the amplitude and time course parameters of signals by exogenous dopamine were increased and Tc was decreased by nomifensine. In contrast, nomifensine did not significantly alter the dopamine signals of the lesioned group. Taken together, in addition to the increased lipid peroxidation in SN, our in vivo electrochemical data demonstrates that iron-induced oxidative injury attenuates K+-evoked dopamine release and dopamine uptake in the ipsilateral striatum. The diminished nomifensine effect implies a lack of high-affinity dopamine uptake sites.

The dorsal facial area of the medulla in cats: inhibitory action of serotonin on glutamate release in regulating common carotid blood flow ☆

Whether glutamate and serotonin would release and interact in the dorsal facial area (DFA) of cat medulla to regulate common carotid arterial (CCA) blood flow was explored by placing a microdialysis probe in DFA and employing high performance liquid chromatographic technique. Glutamate concentration was dose-dependently decreased by perfusion with serotonin, or alaproclate, a serotonin reuptake inhibitor. Serotonin and glutamate concentrations were increased by perfusion with KCl, a depolarizing agent. Furthermore, CCA blood flow was decreased when glutamate concentration was reduced by serotonin or alaproclate perfusion, and conversely increased when glutamate concentration was increased by KCl perfusion. In conclusion, glutamate and serotonin releases in DFA that involve regulation of CCA blood flow are tonically mediated by nerve terminals. The glutamate release is depressed by the serotonin release.