Koji Inui

Arterial baroreflex inhibition by midbrain periaqueductal grey in anaesthetized rats

Midbrain periaqueductal grey (PAG) provokes the defense reaction when stimulated. The present study was conducted to determine whether, and how, the PAG produces baroreflex inhibition, a feature characterizing the hypothalamic defense reaction. In chloralose-urethane anaesthetized rats, baroreflex vagal bradycardia and baroreflex hypotension were provoked by aortic depressor nerve stimulation. When the PAG was electrically stimulated baroreflex vagal bradycardia was remarkably suppressed; suppression of baroreflex hypotension was observed following bilateral vagotomy. In contrast, chemical stimulation of the PAG by d,l-homocysteic acid microinjection markedly suppressed baroreflex vagal bradycardia but only minimally suppressed baroreflex hypotension. These findings suggest that whereas overall PAG stimulation inhibits not only cardiac but also vascular components of baroreflexes, inhibition of the latter component either depends largely on activation of passing fibers or requires recruitment of a larger number of PAG cell bodies. PAG inhibition of baroreflex vagal bradycardia was not affected following spinal cord transection at C1, indicating that the inhibition was exclusively central in origin and not due to peripheral, prejunctional inhibition of vagal acetylcholine release by increased cardiac sympathetic nerve activities. The PAG inhibition of baroreflexes was greatly attenuated following electrolytic as well as chemical destruction of the parabrachial region. On the other hand, when the PAG was extensively lesioned, baroreflex inhibition produced by hypothalamic defense area stimulation was markedly diminished. PAG excitation thus causes powerful inhibition of arterial baroreflexes which is mediated by the parabrachial region; the PAG also mediates a major fraction of hypothalamic inhibition of the baroreflexes.

Facilitation of the arterial baroreflex by the ventrolateral part of the midbrain periaqueductal grey matter in rats.

1. The effects of stimulation of the ventrolateral part of the midbrain periaqueductal grey matter (PAG) on the arterial baroreflex were investigated in urethane‐chloralose anaesthetized and artificially ventilated rats. 2. Both electrical and chemical stimulation of the ventrolateral PAG provoked hypotension, vagal bradycardia and marked facilitation of baroreflex vagal bradycardia (BVB), which was induced by stimulation of the aortic depressor nerve. The magnitude of ventrolateral PAG facilitation of BVB was 328 +/‐ 193% (n = 34) for electrical stimulation and 243 +/‐ 224% (n = 13) for chemical stimulation. Baroreflex hypotension was slightly augmented during either electrical or chemical stimulation of the ventrolateral PAG in vagotomized rats. 3. Stimulation of the nucleus raphe magnus (NRM) also provoked hypotension, vagal bradycardia and facilitation of BVB. The magnitude of BVB facilitation was 234 +/‐ 132% (n = 8) for electrical stimulation and 328 +/‐ 170% (n = 7) for chemical stimulation. After microinjection of kainic acid into the NRM region, baroreflex facilitation, as well as hypotension and vagal bradycardia, produced by ventrolateral PAG stimulation, was almost abolished. 4. In conclusion, the ventrolateral PAG, besides producing hypotension and bradycardia, facilitates arterial baroreflexes. These effects are exerted via the NRM, sharply contrasting with effects of the dorsal PAG.

Baroreceptor inhibition of the locus coeruleus noradrenergic neurons

The locus coeruleus is involved in the regulation of blood pressure. The present study was undertaken to address the question of how the blood pressure, in turn, changes the activity of the locus coeruleus neurons via the action of baroreceptors. In chloralose- and urethane-anesthetized rats, the central cut end of the aortic depressor nerve, which does not contain chemoreceptor afferents in this species, was stimulated electrically to excite baroreceptor afferents after bilateral vagotomy and sectioning of the carotid sinus nerve. Single train-pulse stimulation of the aortic depressor nerve provoked the inhibition of ongoing activity in 48% of locus coeruleus neurons tested, but 30% of them responded by excitation with subsequent inhibition. However, when the train-pulse stimulation was repeated with a frequency of 5 Hz, which is close to that of the heartbeat in the rat, all neurons were markedly inhibited. Another series of experiments was conducted in vagotomized and carotid sinus nerve-sectioned rats with intact aortic depressor nerves. When blood pressure was elevated by an intravenous injection of a pressor agent, methoxamine or angiotensin II, or by rapid blood loading, ongoing activities of all locus coeruleus neurons tested were suppressed. In contrast, intravenously injected nitroprusside, a depressor agent, increased the activity of locus coeruleus neurons. In rats with all nerves preserved, rapid blood loading markedly inhibited the activity of these neurons. Such inhibition was partially but significantly attenuated by bilateral sectioning of the aortic depressor nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Facilitation of the arterial baroreflex by the preoptic area in anaesthetized rats.

1. Activation of cell bodies in the ventrolateral part of the midbrain periaqueductal grey matter (PAG) facilitates the arterial baroreflex via the nucleus raphe magnus. The facilitatory effects of stimulation within the hypothalamus on the arterial baroreflex and their relation to the PAG and nucleus raphe magnus were studied in urethane‐ and chloralose‐anaesthetized rats. 2. Systematic mapping experiments revealed that the preoptic area (POA) is the principal location in the hypothalamus of neuronal cell bodies that are responsible for the potentiation of the baroreflex. In addition to provoking hypotension and vagal bradycardia, both electrical and chemical stimulation of the POA produced facilitation of baroreflex vagal bradycardia (BVB) that was evoked by electrical stimulation of the aortic depressor nerve. Baroreflex hypotension was slightly augmented during activation of the POA in vagotomized rats. 3. Selective destruction of cell bodies either in the ventrolateral PAG or in the nucleus raphe magnus reduced facilitation of BVB by the POA. Hypotension and bradycardia due to POA stimulation were also markedly attenuated after such selective destruction. 4. In conclusion, the POA, the ventrolateral PAG and the nucleus raphe magnus constitute a functional complex that produces cardiovascular trophotropic effects including hypotension, vagal bradycardia and baroreflex facilitation.

Arterial baroreflex inhibition by uterine distension in rats

Arterial baroreflexes are inhibited during activation of some viscero-sensory receptors. The present study was designed to determine whether stimulation of mechanoreceptors of the uterus also inhibits the baroreflex bradycardia (BB). The aortic depressor nerve (ADN) was electrically stimulated to elicit BB in chloralose/urethane-anesthetized, succinylcholine-immobilized, and artificially ventilated rats. Hydraulic distension of the uterus with warm 0.9% NaCl solution was found to suppress BB with a threshold intra-uterine pressure of 25-100 mmHg. The inhibition was variably affected by successive transections of the hypogastric nerve (HgN) and the pelvic nerve (PN). In 6 rats out of the 16 tested, preceding transection of either HgN or PN (HgN, 4; PN, 2) abolished the inhibition, whereas in 8 rats the inhibition was not affected by preceding transection of either nerve but was abolished by subsequent transection of the other nerve (PN, 3; HgN, 5). In 2 rats, preceding HgN or PN section reduced the inhibition and subsequent PN or HgN section completed the withdrawal of the inhibition. Recording study confirmed that both the HgN and PN contain afferent fibers, signalling mechanoceptive information arising in the uterine wall. Electrical stimulation of the HgN as well as the PN remarkably suppressed the BB. In conclusion, uterine distension suppresses the BB and this inhibition is mediated by afferent fibers running in the HgN and PN with variable contributions among animals. The reflex suppression of BB due to uterine sensory activation may contribute to cardiovascular regulation during parturition.

Temporal slow waves and cerebrovascular diseases

Abstract Sporadic temporal slow waves are considered to be associated with mild cerebrovascular dysfunction. However, electroencephalogram (EEG) changes have not been consistently described by some investigators and correlations inferred on the basis of such data remain inconclusive. In the present study, we examined previously defined temporal slow waves in patients in relation to incidence of cerebrovascular disease. A total of 512 EEG were analyzed during a 1 year period at our laboratory and 74 reference EEG from healthy volunteers were all examined as to the presence of temporal low‐voltage irregular delta wave (TLID), temporal minor slow and sharp activity (TMSSA) or bursts of rhythmical temporal theta (BORTT). The patterns were assessed in relation to clinical histories of patients and controls. There were similarities in clinical correlations for the three EEG changes including associations with mild cerebrovascular diseases and with aging. In addition these temporal EEG findings shared electrographic features and showed left side predominance as well as correlating with each other. Since TLID, TMSSA and BORTT have many clinical and electrographical similarities, we consider that these findings should be grouped into one EEG entity which appears in association with mild cerebrovascular dysfunction.

EEG findings in diabetic patients with and without retinopathy

Objectives– We showed previously that temporal low‐voltage irregular delta waves (TLID) on EEG are indicative of cerebrovascular dysfunction in its early stages. The present study was designed to determine whether the incidence of this finding is elevated in diabetics as compared to normal controls. Methods– EEGs of 50 diabetics and 50 normal controls were examined. Relationships of blood sugar levels, levels of HbA1C and stages of diabetic retinopathy to TLID were also examined. Results– TLID was found in 56% of EEGs of the diabetics and in 14% of EEGs of the controls (P <0.0001). The occurrence of TLID was also associated with the presence of diabetic retinopathy. Conclusions– Our results suggest that the incidence of cerebrovascular dysfunction is elevated in diabetics. Since TLID was associated with diabetic retinopathy, it seems possible that the TLID detected in diabetics might reflect certain functional changes induced by microangiopathy of the brain.

DECREASED EXPRESSION OF THE MRNA FOR SOMATOSTATIN IN THE PERIVENTRICULAR NUCLEUS OF DEPRESSION-MODEL RATS

Expression of the mRNA for somatostatin (SRIF) in the periventricular nucleus (PeN), the level of SRIF in the stalk-median eminence (SME) and the concentration of growth hormone (GH) in the plasma were examined in depression-model rats in an attempt to confirm the hypothesis that SRIF neurons in the hypothalamus are hypofunctional in this model. We exposed male Wistar rats to intermittent walking stress for two weeks and then we measured their spontaneous running activity for 12 days. We divided the rats into a depression-model group and a partial-recovery group according to the spontaneous running activity of each rat after the termination of exposure to stress. Expression of SRIF mRNA in the PeN of the hypothalamus was monitored by in situ hybridization and relative levels were determined with an image analysis system. The relative level of expression of SRIF mRNA in the PeN was lower in rats in the depression-model group than in the control group and the partial-recovery group. The level of SRIF in the SME was lower and the plasma concentration of GH was higher in the depression-model group than in the other groups. Our findings suggest that reduced expression of mRNA for SRIF in the PeN might be associated with the pathophysiology of rats with this particular model of depression.

Temporal Delta Wave and Ischemic Lesions on MRI

Abstract: The present study was designed to determine the clinical significance of a temporal low‐voltage irregular delta wave (TLID) on EEG. Among 808 EEG records examined during one year at our hospital, the TLID was commonly detected in patients with clinically diagnosed ischemic brain diseases such as multiple infarction. Subsequently, a relation of the TLID to ischemic lesions on MRI was examined in 50 elderly depressive patients. It was found that there was a close correlation between the occurrence of the TLID and small ischemic lesions on MRI (p<0.001). These results suggest that the TLID is a valuable indicator of minor ischemic changes of the brain.

Use of tripolar electrodes for minimization of current spread in uncut peripheral nerve stimulation

The electrical stimulation of an uncut peripheral nerve requires a countermeasure to avoid the spread of current through a loop pathway formed outside the electrode array. Here the use of tripolar electrodes (TE) is proposed. By binding the two end poles, current spread through the loop pathway can theoretically be eliminated since both end poles are held equipotential. Experimentally, we tested the validity of this approach. In chloralose-urethane anesthetized rats, the left cervical vagus (LCV) was placed on TE which could function as such or as bipolar electrodes (BE) by the use of a selector switch. The spread of current to the adjacent tissues (rectus capitis muscle underlying the LCV, and the right cervical vagus (RCV) incised and translocated beside the target, LCV) was compared between TE and BE. When the stimulus intensity was increased, contraction occurred in the capitis muscle with BE, but not TE. Compound spike potentials of A fiber origin were evoked in the non-target RCV on high-intensity stimulation with BE, but not TE. Constant voltage stimulation of the LCV with TE produced bradycardia of the same magnitude as that with BE. In conclusion, constant voltage stimulation using TE can minimize current spread without changing the stimuluss effects.