Urethane-anesthetized Rabbits Research Articles

Anatomic and functional properties of bulboglandularis striated muscle support its contribution as sphincter in female rabbit micturition.

To determine anatomic and functional properties of the bulboglandularis muscle (Bgm) for clarifying its role in micturition in female rabbits. Virgin female rabbits were used to describe the gross anatomy and innervation of the Bgm, to determine the effect of the Bgm contraction on urethral pressure, and to evaluate the Bgm activity during the induced-micturition. Both electromyogram and cystometrogram activity were simultaneously recorded in urethane-anesthetized rabbits. Bladder function was assessed measuring standard urodynamic variables before and after blocking the Bgm activity for approaching its contribution to micturition. The relevance of the Bgm activation for micturition was approached applying lidocaine injections. The Bgm was composed of circularly oriented striated fibers enveloping distal urethra and pelvic vagina. Both the venous plexus and urethra were comprised by the Bgm contraction induced by electrical stimulation. The Bgm showed bursts of tonic activity at the storage phase of micturition that gradually decreased until turning off as the onset of the voiding phase. The voided volume, the voiding efficiency, the threshold pressure, and the maximal pressure were decreased after lidocaine injection. Contrastingly, the threshold volume, the residual volume, the voiding duration, and the urethral resistance at voiding were increased. Present anatomical and physiological findings support that the Bgm acts as a sphincter during micturition of female rabbits. Neurourol. Urodynam. 35:689-695, 2016. © 2015 Wiley Periodicals, Inc.

ANG II modulates both slow and rapid baroreflex responses of barosensitive bulbospinal neurons in the rabbit rostral ventrolateral medulla

This study investigated the effects of ANG II on slow and rapid baroreflex responses of barosensitive bulbospinal neurons in the rostral ventrolateral medulla (RVLM) in urethane-anesthetized rabbits to determine whether the sympathetic baroreflex modulation induced by application of ANG II into the RVLM can be explained by the total action of ANG II on individual RVLM neurons. In response to pharmacologically induced slow ramp changes in mean arterial pressure (MAP), individual RVLM neurons exhibited a unit activity-MAP relationship that was fitted by a straight line with upper and lower plateaus. Iontophoretically applied ANG II raised the upper plateau without changing the slope, and, thereby, increased the working range of the baroreflex response. An asymmetric sigmoid curve that was determined by averaging individual unit activity-MAP relationship lines became more symmetric with ANG II application. The characteristics of the average curves, both before and during ANG II application, were consistent with the renal sympathetic nerve activity-MAP relationship curves obtained under the same experimental conditions. ANG II also affected rapid baroreflex responses of RVLM neurons that were induced by cardiac beats, as application of ANG II predominantly raised the average unit activities in the downstroke phase of arterial pulse waves. The present study provides a possible explanation for the ANG II-induced sympathetic baroreflex modulation based on the action of ANG II on barosensitive bulbospinal RVLM neurons. Our results also suggest that ANG II changes both static and dynamic characteristics of baroreflex responses of RVLM neurons.

Slowly adapting pulmonary stretch receptor spike patterns carry lung distension information

Slowly adapting pulmonary stretch receptors (SARs) provide the respiratory and cardiovascular control systems with information regarding the rate and depth of breathing. Previous information theoretical analysis demonstrated that SAR spike count provides a reliable representation of lung distension. This study examines whether SAR spike patterns may also provide information about lung distension. To investigate this, artificial spike trains were generated with the same number of spikes (but randomized intervals) as those recorded from SARs in response to three different lung inflation volumes in urethane-anesthetized rabbits. Three different spike train classification methods were applied to estimate which stimulus evoked them, and the accuracy with which artificial spike trains were classified was compared to that of real SAR spike trains using the same methods. Because real SAR spike trains were classified with higher accuracies than artificial ones containing the same number of spikes, we conclude that SAR spike patterns, in addition to spike counts, contain information concerning the amplitude of lung distension.

Vestibular control of arterial blood pressure during head-down postural change in anesthetized rabbits

This study was undertaken to elucidate neural control of the arterial blood pressure (ABP) in head-down postural change which causes both stimulation to the vestibular system and head-ward fluid shift. Experiments were carried out with urethane-anesthetized rabbits. The animal was mounted on a tilting table, tilted to 45 degrees head-down in 5 s, and kept at the position for 5 min. The head-down rotation (HDR) induced a transient decrease in ABP (10 +/- 3 mmHg; mean +/- SE), and then the pressure gradually recovered toward the pre-HDR level during the 5 min at the head-down position. Pretreatment with hexamethonium bromide, a ganglionic transmission blocker, suppressed the HDR-induced drop of ABP, suggesting that the ABP drop was induced by an inhibition of autonomic neural outflows. Renal sympathetic nerve activity (RSNA) decreased considerably after 1.6 +/- 0.2 s from the onset of HDR, which was followed by the ABP drop. Aortic depressor nerve activity (ADNA), an afferent for baroreceptor reflex, increased significantly during the rotation, but the peak of ADNA increase was 3.2 +/- 0.5 s after the initiation of the HDR. Therefore, the suppression of RSNA seems to be induced mainly by a quicker mechanism than baroreceptor reflex. In order to test the possibility, we examined changes in ABP and RSNA during HDR using vestibular-lesioned rabbits. In these rabbits, RSNA and ABP did not change significantly during HDR. These results suggest that vestibular organs play a role in the transient drop in ABP induced by HDR through the suppression of sympathetic nerve outflows.

Identification of c-Fos immunoreactive brainstem neurons activated during fictive mastication in the rabbit

In the present study we used the expression of the c-Fos-like protein as a "functional marker" to map populations of brainstem neurons involved in the generation of mastication. Experiments were conducted on urethane-anesthetized and paralyzed rabbits. In five animals (experimental group), rhythmical bouts of fictive masticatory-like motoneuron activity (cumulative duration 60-130 min) were induced by electrical stimulation of the left cortical "masticatory area" and recorded from the right digastric motoneuron pool. A control group of five animals (non-masticatory) were treated in the same way as the experimental animals with regard to surgical procedures, anesthesia, paralysis, and survival time. To detect the c-Fos-like protein, the animals were perfused, and the brainstems were cryosectioned and processed immunocytochemically. In the experimental group, the number of c-Fos-like immunoreactive neurons increased significantly in several brainstem areas. In rostral and lateral areas, increments occurred bilaterally in the borderzones surrounding the trigeminal motor nucleus (Regio h); the rostrodorsomedial half of the trigeminal main sensory nucleus; subnucleus oralis-gamma of the spinal trigeminal tract; nuclei reticularis parvocellularis pars alpha and nucleus reticularis pontis caudalis (RPc) pars alpha. Further caudally-enhanced labeling occurred bilaterally in nucleus reticularis parvocellularis and nucleus reticularis gigantocellularis (Rgc) including its pars-alpha. Our results provide a detailed anatomical record of neuronal populations that are correlated with the generation of the masticatory motor behavior.

Spinal 5-HT2A receptors regulate cutaneous sympathetic vasomotor outflow in rabbits and rats; relevance for cutaneous vasoconstriction elicited by MDMA (3,4-methylenedioxymethamphetamine, “Ecstasy”) and its reversal by clozapine

We determined whether spinal 5-hydroxytryptamine 2A (5-HT2A) receptors contribute to resting cutaneous sympathetic vasomotor activity, and to increases in activity elicited by electrical stimulation of the medullary raphe/parapyramidal region, and whether these receptors are involved in the cutaneous vasoconstricting action of systemically administered MDMA (3,4-methylenedioxymethamphetamine, “Ecstasy”) and its reversal by clozapine. Experiments were conducted in urethane-anesthetized rabbits and rats. Administration of the 5-HT2A antagonist, trans-4-((3 Z)3-[(2-Dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate (SR 46349B, 0.1 mg/kg, i.v.) inhibited resting ear pinna sympathetic vasomotor nerve discharge and reduced the extent to which raphe/parapyramidal electrical stimulation caused ear pinna (rabbit) and tail (rat) artery blood flow to fall. Clozapine (0.125–0.5 mg/kg, i.v.) also reduced the fall in ear pinna blood flow elicited by raphe/parapyramidal stimulation. In rabbits, after inactivation of raphe/parapyramidal function by local microinjection of muscimol (1 nmol in 100 nl), the 5-HT2A agonist R(−)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI, 50 μg/kg, i.v.) increased ear pinna sympathetic nerve activity from 3±2% to 129±5% of pre-muscimol levels ( P<0.01, n=6), and this increase was abolished by section of the ipsilateral cervical sympathetic nerve trunk. MDMA (2 mg/kg, i.v.) after muscimol decreased ear pinna blood flow from 33±10 to 2±1 cm/s ( P<0.01, n=5) and increased ear pinna sympathetic nerve activity from 8±4% to 120±41% of pre-muscimol levels ( P<0.01, n=6). The MDMA-elicited increase in nerve activity was abolished by SR 46349B. Data suggest that spinal 5-HT2A receptors contribute to sympathetically induced cutaneous vasoconstriction regulated by raphe/parapyramidal neurons in the brainstem, and that these receptors contribute to the cutaneous vasoconstricting action of MDMA and its reversal by clozapine.

Clozapine Reverses Hyperthermia and Sympathetically Mediated Cutaneous Vasoconstriction Induced by 3,4-Methylenedioxymethamphetamine (Ecstasy) in Rabbits and Rats

Life-threatening hyperthermia occurs in some individuals taking 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). In rabbits, sympathetically mediated vasoconstriction in heat-exchanging cutaneous beds (ear pinnae) contributes to MDMA-elicited hyperthermia. We investigated whether MDMA-elicited cutaneous vasoconstriction and hyperthermia are reversed by clozapine and olanzapine, atypical antipsychotic agents. Ear pinna blood flow and body temperature were measured in conscious rabbits; MDMA (6 mg/kg, i.v.) was administered; and clozapine (0.1-5 mg/kg, i.v.) or olanzapine (0.5 mg/kg, i.v.) was administered 15 min later. One hour after MDMA, temperature was 38.7 +/- 0.5 degrees C in 5 mg/kg clozapine-treated rabbits and 39.0 +/- 0.2 degrees C in olanzapine-treated rabbits, less than untreated animals (41.5 +/- 0.3 degrees C) and unchanged from pre-MDMA values. Ear pinna blood flow increased from the MDMA-induced near zero level within 5 min of clozapine or olanzapine administration. Clozapine-induced temperature and flow responses were dose-dependent. In urethane-anesthetized rabbits, MDMA (6 mg/kg, i.v.) increased ear pinna postganglionic sympathetic nerve discharge to 217 +/- 33% of the pre-MDMA baseline. Five minutes after clozapine (1 mg/kg, i.v.) discharge was reduced to 10 +/- 4% of the MDMA-elicited level. In conscious rats made hyperthermic by MDMA (10 mg/kg, s.c.), body temperature 1 hr after clozapine (3 mg/kg, s.c.) was 36.9 +/- 0.5 degrees C, <38.6 +/- 0.3 degrees C (Ringer's solution-treated) and not different from the pre-MDMA level. One hour after clozapine, rat tail blood flow was 24 +/- 3 cm/sec, greater than both flow in Ringer's solution-treated rats (8 +/- 1 cm/sec) and the pre-MDMA level (17 +/- 1 cm/sec). Clozapine and olanzapine, by interactions with 5-HT receptors or by other mechanisms, could reverse potentially fatal hyperthermia and cutaneous vasoconstriction occurring in some humans after ingestion of MDMA.

Vestibularly evoked climbing-fiber responses modulate simple spikes in rabbit cerebellar Purkinje neurons.

The nodulus receives a primary vestibular afferent input from the ipsilateral labyrinth and a vestibularly related climbing-fiber input originating from the contralateral labyrinth. Previously we demonstrated that increased discharge of vestibularly evoked climbing-fiber responses (CFRs) in nodular Purkinje cells was correlated with decreased discharge of simple spikes (SSs). This left unresolved the question of whether vestibularly evoked antiphasic behavior of CFRs and SSs reflects a common neural mechanism or the activation of two separate parallel pathways. We answered this question using natural vestibular stimulation to modulate the discharge of uvula-nodular Purkinje cells recorded extracellularly in unilaterally labyrinthectomized, chloralose urethane-anesthetized rabbits. In such animals, vestibular primary afferents projecting to the uvula-nodulus as mossy fibers remained intact on the side contralateral to the unilateral labyrinthectomy. The discharge of CFRs recorded in ipsilateral nodular Purkinje cells was increased by ipsilateral roll-tilt while the discharge of SSs was increased by contralateral roll-tilt. These polarities were reversed for Purkinje cells recorded in the contralateral uvula-nodulus. The polarity of SS discharge recorded from Purkinje cells on both sides of the nodulus was opposite to that of the vestibular primary mossy-fiber afferents. SSs continued to respond to contralateral roll-tilt even when the primary vestibular afferent mossy-fiber pathway was destroyed by the unilateral labyrinthectomy. Although the discharge of SSs recorded in the contralateral uvula-nodulus was increased by contralateral roll-tilt, this modulation was reduced relative to that observed in Purkinje cells recorded in the ipsilateral uvula-nodulus. We conclude that vestibularly evoked CFRs caused the modulation of SS discharge.

Effects of kallidinogenase on ocular tissue circulation in rabbits.

The purpose of this study is to evaluate the effects of kallidinogenase, a tissue kallikrein, on tissue circulation in the optic nerve head (ONH), choroid and retina. Kallidinogenase (1.0 IU/kg) or saline was injected intravenously into urethane-anesthetized rabbits, and the normalized blur value (NB), a quantitative index of in vivo tissue blood velocity, was measured in the ONH, choroid and retina before and for 90 minutes after injection, using the laser speckle method. The difference in NB values in the kallidinogenase group was significantly higher compared with that in the control group in the choroid (p < 0.05) and retina (p < 0.05, ANOVA of repeated measurements). In the ONH, however, there was no significant difference between the kallidinogenase group and the control group except transient increment 10 min after drug administration (p < 0.01, unpaired t-test). On the other hand, systemic condition parameters and intraocular pressure showed no intergroup difference significantly except for a transient decrease in blood pressure and increase in pulse rate in the kallidinogenase groups. Kallidinogenase increased blood velocity, and probably blood flow, in the choroid and retina of rabbits.

Relative importance of rostral ventrolateral medulla in sympathoinhibitory action of rilmenidine in conscious and anesthetized rabbits.

The pressor region of the rostral ventrolateral medulla (RVLM) is a critical site in the sympathoinhibitory action of imidazoline receptor agonists as shown by studies in anesthetized animals. The aim of this study was to compare the importance of the RVLM in mediating the inhibitory action of rilmenidine on renal sympathetic nerve activity (RSNA) and arterial pressure in urethane-anesthetized rabbits (n = 11) and in conscious, chronically instrumented rabbits (n = 6). Bilateral microinjection of rilmenidine (4 nmol in 100 nl) into the RVLM caused a greater decrease in resting arterial pressure in anesthetized animals (-19 mm Hg) than in conscious animals (-8 mm Hg). By contrast, the decrease in resting RSNA evoked by rilmenidine was similar in conscious (-27%) and anesthetized (-36%) rabbits. Furthermore, rilmenidine microinjection into the RVLM was equally effective in inhibiting the RSNA baroreflex in both groups of animals. The upper plateau of the RSNA baroreflex decreased by 37% and 42%, and gain decreased by 41% and 44% after rilmenidine treatments in conscious and anesthetized rabbits, respectively. We conclude that the RVLM plays an equally important role in the inhibitory action of rilmenidine on RSNA in conscious and anesthetized rabbits either at rest or during baroreflex responses. A relatively moderate effect of rilmenidine on arterial pressure in conscious, chronically instrumented rabbits may relate to a lower level of sympathetic drive compared with anesthetized animals.

Effects of induced hypothermia on renal sympathetic nerve activity and baroreceptor reflex in urethane-anesthetized rabbits.

To evaluate the role of the autonomic nervous system in hemodynamic changes during induced hypothermia. Prospective, randomized animal study. An animal research laboratory in a medical university. A total of 29 anesthetized rabbits. Animals were anesthetized by intraperitoneal urethane. After tracheostomy and administration of gallamine, respiration was maintained by mechanical ventilatory support. The animals were divided into five groups (one control and the four experimental groups); animals were treated with an intact neuraxis and normothermia (control group), animals with an intact neuraxis (intact group), cervical vagotomized animals (vagotomy group), the carotid sinus and aortic nerves denervated animals (SAD group), and animals with SAD plus vagotomy (SADV group). The left renal sympathetic nerves were exposed by a retroperitoneal approach. We examined the effects of surface cooling on HR, mean arterial pressure, central venous pressure, and renal sympathetic nerve activity (RSNA) in the animals. Changes of baroreflex sensitivity and plasma catecholamines were also measured simultaneously. Surface cooling caused progressive and profound decreases in HR in all experimental groups. In all groups, RSNAs increased at the early phase, which were followed by return to the precooling level. Hemodynamics and RSNA during induced hypothermia are regulated by mechanisms other than the baroreceptor reflex system, possibly the dermal cold receptors. Suppression of the baroreflex occurred on HR but not on RSNA during hypothermia, which may indicate direct effects of hypothermia on the heart. RSNA responses may be activated earlier than systemic catecholamine responses during induced hypothermia.

Effects of Semotiadil, A Novel Calcium Antagonist, on the Retina and Optic Nerve Head Circulation

The effects of semotiadil, a novel benzothiazine calcium antagonist, on the retinal and optic nerve head (ONH) tissue circulation were evaluated using the noninvasive laser speckle method. In urethane-anesthetized Dutch or albino rabbits, before and up to 90 min following intravenous injection of 400 microg/kg semotiadil fumarate (semotiadil group) or vehicle (control group), normalized blur value, a quantitative index of tissue blood velocity, in the retina (NB(retina)) or ONH (NB(onh)), was serially obtained with monitoring intraocular pressure (IOP) and systemic parameters: arterial pressure, pulse rate, arterial blood gas, and body temperature. There were no significant differences in IOP and the systemic parameters except arterial pressure between semotiadil and control groups during the experiments. Arterial pressure showed an acute and transient drop during the first 5 min after semotiadil administration. The time courses of the normalized blur value were significantly different between semotiadil and control groups in the retina (P = 0.0001, repeated measures two-way ANOVA), but not in the ONH (P = 0.6724). Changes in NB(retina) from the baseline in the semotiadil group was significantly greater than those in the control group 50 min or later after the administration (P < 0.0500, Mann-Whitney test). NB(onh) showed no significant differences between the two groups except during the first few min when arterial pressure acutely decreased in the semotiadil group. In conclusion, intravenously injected semotiadil increased the tissue blood velocity in the retina, but not in the ONH. This vascular selectivity in the ocular neural tissues differs from those of other calcium antagonists, such as nicardipine.

Dose-dependent effects of propofol on renal sympathetic nerve activity, blood pressure and heart rate in urethane-anesthetized rabbits

To evaluate the role of the autonomic nervous system in hemodynamic changes after propofol bolus injection, we used direct recordings of renal sympathetic nerve activity to examine the dose-dependent effects of propofol (2.5, 5, 10, and 20 mg/kg) on heart rate, mean blood pressure and renal sympathetic nerve activity in urethane-anesthetized rabbits. The animals were divided into four groups: animals with an intact neuraxis (intact group), cervical vagal nerve-sectioned animals (vagotomy group), carotid sinus and aortic-nerve sectioned animals (SAD group), and animals with SAD plus vagotomy (SADV group). Heart rate did not change significantly even after administration of 2.5 and 5 mg/kg but decreased markedly on 20 mg/kg injection in all groups. The intact and vagotomy groups had augmented renal sympathetic nerve activity with insignificant changes in mean blood pressure after 5 mg/kg injection of the agent. Insignificant changes of renal sympathetic nerve activity but a remarkable decrease of mean blood pressure appeared after 10 mg/kg propofol. Sustained hypotension in parallel with a profound depression of renal sympathetic nerve activity developed at the dose of 20 mg/kg. In SAD and SADV groups, however, dose-dependent depressions of renal sympathetic nerve activity were accompanied by decreases of mean blood pressure. These results suggest the following: (1) propofol-induced hypotensive effects are probably produced by the central-mediated sympathetic depression. (2) The baroreceptor reflex may be preserved at the lower dose of the agent. (3) Heart rate does not change significantly unless a large dose of propofol is used. The difference in effects on heart rate and on mean blood pressure may denote a greater inhibition of sympathetic vascular outflow than of the cardiac sympathetic outflow regulating cardiac rate and contractility. This hypothesis needs further clarification.

Synchronized oscillatory discharges of mitral/tufted cells with different molecular receptive ranges in the rabbit olfactory bulb.

Individual glomeruli in the mammalian olfactory bulb represent a single or a few type(s) of odorant receptors. Signals from different types of receptors are thus sorted out into different glomeruli. How does the neuronal circuit in the olfactory bulb contribute to the combination and integration of signals received by different glomeruli? Here we examined electrophysiologically whether there were functional interactions between mitral/tufted cells associated with different glomeruli in the rabbit olfactory bulb. First, we made simultaneous recordings of extracellular single-unit spike responses of mitral/tufted cells and oscillatory local field potentials in the dorsomedial fatty acid-responsive region of the olfactory bulb in urethan-anesthetized rabbits. Using periodic artificial inhalation, the olfactory epithelium was stimulated with a homologous series of n-fatty acids or n-aliphatic aldehydes. The odor-evoked spike discharges of mitral/tufted cells tended to phase-lock to the oscillatory local field potential, suggesting that spike discharges of many cells occur synchronously during odor stimulation. We then made simultaneous recordings of spike discharges from pairs of mitral/tufted cells located 300-500 microm apart and performed a cross-correlation analysis of their spike responses to odor stimulation. In approximately 27% of cell pairs examined, two cells with distinct molecular receptive ranges showed synchronized oscillatory discharges when olfactory epithelium was stimulated with one or a mixture of odorant(s) effective in activating both. The results suggest that the neuronal circuit in the olfactory bulb causes synchronized spike discharges of specific pairs of mitral/tufted cells associated with different glomeruli and the synchronization of odor-evoked spike discharges may contribute to the temporal binding of signals derived from different types of odorant receptor.

Neurogenic origin of articular hyperemia in early degenerative joint disease.

It has been speculated that joint instability resulting from anterior cruciate ligament (ACL) rupture could be exacerbated by changes in vasomotor activity in the remaining supporting structures. In this study, the effect of ACL transection on medial collateral ligament (MCL) basal perfusion and its responsiveness to calcitonin gene-related peptide (CGRP) and sympathetic adrenergic influences was examined. Using urethan-anesthetized rabbits, we tested the effects of CGRP and its antagonist CGRP-(8-37) by topical application of these agents to the exposed knee while sympathetic influences were tested by electrically stimulating the saphenous nerve. It was found that MCL basal perfusion was elevated in ACL-sectioned joints; however, this effect was abrogated by prior resection of the articular nerve supply. At the doses tested, the normal vasodilator response to CGRP was abolished in ACL-sectioned joints, whereas the response to CGRP-(8-37) was attenuated. Even under the influence of increased constrictor tone, MCL and capsule blood vessels still showed substantially reduced responses to exogenous CGRP administration. By contrast, nerve-mediated constrictor responses were mostly unaffected by joint instability. This study suggests that posttraumatic knee joint hyperemia is neurogenically mediated, possibly by increased secretion of CGRP.

Effects of pranidipine, a new calcium antagonist, on circulation in the choroid, retina and optic nerve head

PURPOSE. To study the effects of pranidipine, a newly developed Ca 2+ -antagonist, on tissue circulation in the optic nerve head (ONH), choroid, and retina in rabbits. METHODS. Pranidipine (5 µg/kg) or vehicle solution was injected intravenously in urethane-anesthetized rabbits and the normalized blur value (NB), a quantitative index of in vivo tissue blood velocity, was measured in the choroid and in an area of the ONH and retina free of visible surface vessels before and for 90 min after injection, using the laser speckle method. Measurements in the ONH and choroid were performed in the same albino rabbit eyes (pranidipine group, n = 10; control group, n = 10) and those in the retina in another group of Dutch rabbits (pranidipine group, n = 10; control group, n = 10). RESULTS. Between 30 and 90 min after injection, the NB in the pranidipine group increased by 24% in the ONH, 19% in the choroid, and 17% in the retina on an average compared to baseline, and was significantly different from that in the control group (P < 0.0001, ANOVA). There were no significant inter-group differences in the systemic parameters, except for a transient decrease in blood pressure in the pranidipine groups. CONCLUSIONS. Pranidipine increased blood velocity and probably blood flow in the ONH, choroid, and retina of rabbits.

P–249 - Effects of some vasopressors on chlorpromazine-induced orthostatic hypotension in urethane-anesthetized rabbits.

P–249 - Effects of some vasopressors on chlorpromazine-induced orthostatic hypotension in urethane-anesthetized rabbits.

Effects of dexmedetomidine, an α2-adrenoceptor agonist, on renal sympathetic nerve activity, blood pressure, heart rate and central venous pressure in urethane-anesthetized rabbits

To clarify the role of the neural blood pressure control system in hemodynamic changes after dexmedetomidine (DXM) administration, we examined the effects of an intravenous injection of DXM (10 μg/kg) on heart rate (HR), mean blood pressure (MBP), central venous pressure (CVP) and renal sympathetic nerve activity (RNA) in urethane-anesthetized rabbits using direct recordings of RNA. The animals were divided into four groups: animals with an intact neuraxis (intact group; n=12), cervical vagotomized animals (vagotomy group; n=5), sino-aortic denervated animals (SAD group; n=5), and animals with SAD plus vagotomy (SADV group; n=5). An initial HR decrease, which occurred in the intact group, did not occur in the other three groups, suggesting the mediation of the baroreflex. A subsequent HR decrease occurred in the three groups other than the vagotomy group, in which RNA recovered earlier than in the other groups. RNA in the intact group, associated with transient hypertension, was suppressed shortly after the injection. Such an RNA drop was not eliminated even in the SADV group. Despite recovery of RNA, hypotension lasted until the end of experiment in the intact and vagotomy groups. However, sustained depression of RNA associated with lasting hypotension was found in the SAD and SADV groups. CVP in all groups did not change significantly after the injection. These results suggest the following: (1) Initial bradycardia after DXM is mediated via the baroreflex. Subsequently, HR reductions may result mainly from central sympathetic depression. (2) An initial reduction in RNA is not mediated via the baroreceptor reflex, unlike HR responses, but by central sympatho-inhibitory effects. (3) Long-lasting hypotension after DXM is likely to be attributable to its peripheral vascular effects including the stimulation of pre-synaptic α 2-adrenoceptors, rather than to central sympathetic depression.

Influence of endothelin-1 on clonidine-induced cardiovascular effects in anesthetized rabbits.

This study was designed to investigate the effect of endothelin-1 (ET-1) on clonidine-induced cardiovascular effects in urethane-anesthetized rabbits and to clarify the mechanism of its action. Clonidine (5, 10, and 20 micrograms/kg) given into a femoral vein (i.v.) produced a marked dose-dependent fall in arterial blood pressure and heart rate, but intracerebroventricular (i.c.v.) clonidine (2, 4, and 8 micrograms/kg) induced a slight depressor effect and bradycardia. Intravenous clonidine-induced hypotension was significantly enhanced by pretreatment with ET-1 or sarafotoxin, but the bradycardia was not affected. Intracerebroventricular clonidine-induced depressor responses were greatly inhibited by sarafotoxin pretreatment but not by ET-1. Both i.v. and i.c.v. ET-1 and sarafotoxin elicited marked hypotensive responses, with a slight decrease in heart rate. The depressor action evoked by i.v. ET-1 and sarafotoxin was significantly inhibited by nitroprusside but not by phentolamine or sodium acetylsalicylate. Furthermore, the weak bradycardia induced by ET-1 or sarafotoxin was not influenced by pretreatment with phentolamine, nitroprusside, or sodium acetylsalicylate. Taken together, these experimental data suggest that ET-1 potentiates clonidine-induced hypotensive responses in the urethane-anesthetized rabbit through facilitation of nitric oxide release, which appears to be associated with endothelin receptors.

Dynamic transduction properties of in situ baroreceptors of rabbit aortic depressor nerve.

We developed a new method for isolating in situ baroreceptor regions of the rabbit aortic depressor nerve (ADN) and estimated the transfer function from pressure to afferent nerve activity in the frequency range of 0.01-5 Hz by a white noise technique. Complete isolation of the baroreceptor area of the right ADN was made in situ by ligation of the innominate artery and the right subclavian and common carotid arteries. We altered the pressure in the isolated baroreceptor area according to a binary quasi-white noise between 80 and 100 mmHg in 12 urethan-anesthetized rabbits. The gain increased two to three times as the frequency of pressure perturbation increased from 0.01 to 2 Hz and then decreased at higher frequencies. The phase slightly led below 0.2 Hz. The squared coherence value was > 0.8 in the frequency range of 0.01-4 Hz. The step responses estimated from the transfer function were indistinguishable from those actually observed. We conclude that the baroreceptor transduction of the ADN is governed by linear dynamics under the physiological operating pressure range.