Rostral ventrolateral medulla catechol involvement upon sino-aortic deafferentation: an in vivo voltammetric study.

Pharmacologically-induced hypertension engages few aminergic ventrolateral medullary cells. To further address this issue, reflex hypertension evoked by acute sino-aortic deafferentation was chosen as a model. Adrenergic rostral ventrolateral neurons were recorded with a continuous, catechol-specific tool, i.e. in vivo voltammetry. Controlled hypotension led to the expected increase in catechol signal in sham rats (n = 4) but not in deafferented (vagi, superior laryngeal and glossopharyngeal nerves) rats (n = 5). Thus, the central responsiveness to known stimuli remained intact in this preparation following acute sino-aortic deafferentation. However, acute sino-aortic deafferentation itself induced no increase in catechol signal (n = 4 or 5 respectively). No increase in catechol signal was, observed when deafferentation was performed a) under hyperoxic conditions (O2 = 100%, n = 5) b) by extensive deafferentation involving also the cervical sympathetic trunk under halothane (n = 5) c) upon restrictive deafferentation leaving the vagi intact under pentobarbital (n = 5) d) in decerebrate animals (n = 4). Adrenergic rostral ventrolateral medullary barosensitive bulbospinal neurons may be primarily involved during hypotension.

Catechol activation in the vasomotor center upon emergence from anesthesia: specificity.

The rostral ventrolateral medulla (RVLM) controls the vascular system. It may contribute to postoperative hypertension observed upon emergence from anesthesia. This structure contains adrenergic cardiovascular neurons. Therefore, one question was addressed: does a change in RVLM catechol activity occur upon emergence from anesthesia? Halothane-anesthetized, paralyzed rats had their ventilatory, circulatory, and acid-base stability controlled. All pressure points and incisions were infiltrated with local anesthetic. With in vivo electrochemistry, a catechol signal was recorded in the RVLM in the following circumstances: (1) under stable halothane anesthesia for 120 minutes (halothane group), (2) during 120 minutes after halothane discontinuation (saline-emergence group), (3) during 60 minutes after halothane discontinuation followed by 60 minutes after halothane readministration (readministration group), (4) emergence in rats treated with atenolol and nitroprusside to hold blood pressure as close as possible to baseline, (5) emergence after morphine 1 mg.kg(-1) i.v., (6) emergence after decerebration, and (7) emergence upon recording in the mid-brain dopaminergic A10 area. Stable halothane anesthesia (n = 6) led to no change in mean arterial pressure (MAP), heart rate (HR), and catechol signal (CAOC). During emergence from anesthesia (n = 6), MAP, HR, and catechol signal increased and did not return to baseline. By contrast, a return of MAP, HR, and catechol signal to baseline was observed upon readministration of halothane (n = 6). Whereas blood pressure and heart rate were maintained as closely as possible to baseline, a large catechol activation (n = 5) was observed upon emergence from anesthesia. A catechol activation from a lowered baseline was observed upon emergence following morphine administration (n = 5). A minor circulatory activation without RVLM catechol activation was observed upon emergence following decerebration (n = 5). Recordings in the A10 area revealed no increase in the catechol signal following emergence (n = 5). Adrenergic RVLM neurons appear to be responsive upon emergence from anesthesia, possibly being activated by suprapontine afferents impinging on the RVLM.

Catechol activation in rat rostral ventrolateral medulla after systemic isocapnic metabolic acidosis.

The catechol signal recorded using in vivo voltammetry within the rat rostral ventrolateral medulla (RVLM) can be interpreted as a catechol-specific index of the integrated activity of RVLM adrenergic barosensitive bulbospinal and nonbulbospinal neurons. To test the hypothesis that systemic acidosis leads to the activation of RVLM adrenergic neurons, the RVLM catechol signal was observed in rats after mild systemic acidosis (pH 7.20-7.25 for 30 min) induced by 1 M HCl under halothane anesthesia, controlled mechanical ventilation, and continuous infusion of Ringer lactate. Particular attention was paid to ensure that changes in mean arterial pressure (MAP) were <15 mmHg during HCl challenge. Saline administration was not associated with any significant change in all considered variables (n = 5). Mild isocapnic systemic acidosis was associated with an increase in catechol signal (n = 5), irrespective of carotid sinus nerve section (n = 5). In keeping with the aim of the study, there were minor (<15 mmHg) but significant changes in MAP among saline, intact, and deafferented groups. Changes in heart rate were not significant. In conclusion, a catechol activation is observed in the RVLM when arterial pressure is maintained during isocapnic systemic metabolic acidosis. This catechol activation appears primarily centrally mediated. Therefore, adrenergic RVLM neurons may relay inputs from the central respiratory generator to the sympathetic system and/or act as chemosensors for H+ next to the surface of the ventrolateral medulla.

Catecholamine activation in the vasomotor center on emergence from anesthesia: the effects of alpha2 agonists.

UNLABELLED: The rostral ventrolateral medulla (RVLM) controls the vascular system and may contribute to postoperative hypertension. It comprises adrenergic cardiovascular neurons, a site for action of alpha2-adrenergic agonists. Because alpha2 agonists minimize perioperative circulatory activation, we asked the following question: do alpha2 agonists, such as clonidine and mivazerol, blunt the catecholamine activation observed in the RVLM on emergence from anesthesia? Halothane-anesthetized, paralyzed rats had their ventilatory, circulatory, and acid-base stability controlled. All pressure points and incisions were infiltrated with local anesthetics. With in vivo electrochemistry, a catechol signal was recorded in the RVLM during 150 min of stable halothane anesthesia (saline-halothane group); for 120 min after halothane discontinuation (saline-emergence group); after emergence and administration of the reference alpha2 agonist, clonidine 7 microg/kg or 21 microg/kg I.V. (50% or 90% effective dose [ED50 or ED90], respectively); and after emergence and administration of a new alpha2 agonist, mivazerol 20 microg/kg or 150 microg/kg I.V. (ED50 or ED90). Under halothane, dose-response curves for the RVLM catecholamine signal were constructed for mivazerol and an alpha2 antagonist, idazoxan (ED50 2.3 mg/kg I.V.). Stable halothane anesthesia (n = 5) led to no change in mean arterial pressure (MAP), heart rate (HR), or catechol signal (CAOC). During emergence from anesthesia, the MAP, HR, and CAOC increased (n = 5). Clonidine led to a near total suppression of the RVLM catecholamine activation noticed on emergence from anesthesia (n = 5). Hypertension was partially blunted with clonidine 7 microg/kg (n = 5). Tachycardia was partially blunted with mivazerol 20 microg/kg (n = 5). Pretreatment with idazoxan suppressed all the effects of mivazerol (n = 5). IMPLICATIONS: On emergence from anesthesia, alpha2 agonists modify the activity of adrenergic cardiovascular neurons located within the vasomotor center, as assessed by in vivo electrochemistry. We provide a rationale for the use of alpha2 agonists on emergence from anesthesia in coronary/hypertensive patients.

Catechol changes in the rat rostral ventrolateral medulla following changes in systemic CO2.

A catechol signal recorded with in vivo voltammetry within the rat rostral ventrolateral medulla (RVLM) was taken as an index of the activity of RVLM adrenergic neurons and related to the level of arterial PCO2, under halothane anesthesia. Reversible increases in catechol signal were observed during reversible increases in arterial partial CO2 pressure (PaCO2) from 20 to 60 mmHg after alteration of tidal volume (n = 5 intact rats, n = 5 after carotid sinus deafferentation). A reversible increase in inspiratory CO2 combined with constant tidal volume led to changes in PaCO2 from 40 mmHg to 50 or 60 or 70 mmHg for 60 min (n = 5 in each group) and to a reversible increase in catechol signal (r = 0.76). These changes were also observed after carotid sinus deafferentation (PaCO2 = 40 to 60 to 40 mmHg, n = 5). Lowering the PaCO2 from 40 to 20 mmHg led to a minor, nonsignificant reduction in catechol signal (n = 5). Changes in arterial pressure were minimal, although they reached statistical significance in some groups of experiments. The level of catechol metabolism in the RVLM 1) is continuously related to the level of arterial CO2, 2) functions close to its resting level under baseline nonstimulated condition with respect to CO2, and 3) is reversibly modified on changes in capnia. Sensitivity of the catechol signal, recorded in the rostral ventrolateral medulla, to CO2 appears primarily to be centrally mediated. Thus adrenergic RVLM neurons may relay inputs from the central respiratory generator to the sympathetic chemoreflex or act as chemosensors for CO2, next to the ventrolateral medulla surface.

Absence of evidence for a powerful tonic baroreflex-mediated inhibition on catechol activity in the rat rostral ventrolateral medulla: in vivo voltammetric evidence during sino-aortic deafferentation.

To test in a catechol-specific and dynamic manner for the existence of a powerful long-lasting inhibition arising from barosensitive afferents that depresses the activity of adrenergic neurons in the rostral ventrolateral medulla (RVLM), in vivo voltammetry was used before and after acute sino-aortic deafferentation. Rats were anaesthetized with pentobarbital or halothane and ventilated with a mixture of air and oxygen. Snares were inserted around the vagus, the glossopharyngeal and the superior laryngeal nerves. After placing the animal prone in the stereotaxic frame and stabilization at a high mean arterial pressure (MAP approximately 120 mmHg), the snares were rapidly closed to produce complete barodeafferentation, assessed by loss of heart rate responses and changes in renal nerve sympathetic activity in response to vasoactive agents. Recording of a catechol signal was maintained in the RVLM during deafferentation. Under pentobarbital-induced anaesthesia (n = 5), deafferentation did not lead to a significant change in the catechol signal within the deafferented group. Under halothane-induced anaesthesia and phenylephrine-induced high baseline pressure (n = 5), no changes in the catechol signal were observed upon deafferentation (not significant vs. sham animals: n = 5). This failure to demonstrate a major increase in catechol activity upon deafferentation does not fit with the hypothesis that a powerful tonic baroreflex-mediated inhibition depresses the activity of adrenergic RVLM barosensitive bulbospinal neurons, even when the baseline MAP is high. Rather, these data are compatible with weak or no inhibition of catechol activity by the baroreceptors and a nonessential role of adrenergic neurons within the baroreceptor reflex arc itself: the adrenergic neurons may not be in series within this arc but in parallel with the arc. This interpretation is in keeping with newer schemas of autonomic core circuitry that are devoid of adrenergic neurons.

Systemic acidosis after controlled hypotension activates catechol activity in the vasomotor center.

Activation of the catechol metabolism, assessed with in vivo voltammetry, in the vasopressor area of the vasomotor center was investigated during systemic acidosis occurring after controlled hypotension. Rats anesthetized with halothane were mechanically ventilated. Sodium nitroprusside lowered mean arterial pressure to 55 mmHg for > or = 20 min. Arterial blood gases allowed us to group rats according to whether they showed symptoms of metabolic acidosis (pH < or = 7.34) immediately after controlled hypotension. To assess the effect of systemic acidosis independently of the progressive decline in pressure observed during the recovery period after controlled hypotension, we used phenylephrine infusion to maintain mean arterial pressure at baseline pressure during the recovery period after controlled hypotension in two groups of animals. Systemic acidosis increased the catechol signal in a prolonged manner [nitroprusside with acidosis (n = 7) vs. nitroprusside without acidosis (n = 5); P < 0.0001]. This catechol activation was greater when pressure was restored after hypotension [nitroprusside with acidosis plus phenylephrine (n = 5) vs. nitroprusside with acidosis over the whole interval (from -30 to +150 min); P < 0.05]. When the nitroprusside with acidosis group and nitroprusside with acidosis plus phenylephrine group were compared, hypercapnia had an involvement in the larger increase of the catechol signal observed in the nitroprusside with acidosis plus phenylephrine group [arterial PCO2: nitroprusside with acidosis vs. nitroprusside with acidosis plus phenylephrine over the whole interval (from -30 to +150 min) and at +30 and +60 min; all P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)