Yuko Sato

Neural mechanism of depressor responses of arterial pressure elicited by acupuncture-like stimulation to a hindlimb in anesthetized rats.

The effects of acupuncture-like stimulation of a hindlimb on renal sympathetic nerve activity (RNA) as well as mean arterial blood pressure (MAP) were examined in anesthetized rats. An acupuncture needle (diameter of 160 microns) was inserted into the skin of a hindlimb and underlying muscles to a depth of 5 mm and was twisted at about 1 Hz. Under deep anesthetic condition, in about 70% of trials, acupuncture-like stimulation for 60 s induced a decrease in MAP which was accompanied by a decrease in RNA. Acupuncture-like stimulation applied to the muscles alone, but not to the skin alone, induced inhibition of RNA and MAP. Transection of sciatic and femoral nerves ipsilateral to the hindlimb stimulation completely abolished the responses of RNA and MAP. The hindlimb stimulation excited the femoral and common peroneal afferent nerves. In spinalized animals, the hindlimb stimulation did not produce any changes in RNA and MAP. The results indicate that the decrease in MAP induced by acupuncture-like stimulation of a hindlimb is a reflex response. The afferent pathway is composed of hindlimb muscle afferents while the efferent pathway is composed of sympathetic vasoconstrictors including the renal nerves. Endogenous opioids may not be involved in the present reflex, because an intravenous injection of naloxone, an antagonist of the opioid receptors, did not influence the reflex.

Somatocardiovascular reflexes in anesthetized rats with the central nervous system intact or acutely spinalized at the cervical level.

The effects of noxious mechanical stimulation of various segmental areas on heart rate and mean arterial blood pressure (MAP), as well as cardiac and renal sympathetic nerve activities were examined in anesthetized rats with the central nervous system (CNS) intact or acutely spinalized at the cervical level. In CNS-intact rats, pinching for 20 s applied to any segmental skin area, but particularly that of the paw, produced an increase in heart rate, blood pressure and the sympathetic nerve activities. In acutely spinalized rats, pinching the chest, abdomen and back of the body produced large increases, while hindlimb and perineum stimulation induced only a small increase or no increase in heart rate, blood pressure and the sympathetic nerve activities. Stimulation of the right side produced particularly large responses in heart rate and stimulation of the ipsilateral side produced large responses in cardiac and renal sympathetic nerve activities in spinalized rats. These results suggest the existence of the two types of reflex responses, supraspinal and propriospinal, in the somatocardiovascular reflex. The supraspinal one has characteristics of diffuse reflex organization, while the propriospinal one has strong segmental and lateral organization.

Activation of the intracerebral cholinergic nerve fibers originating in the basal forebrain increases regional cerebral blood flow in the rat's cortex and hippocampus.

In the rat, activation of the intracerebral cholinergic system originating in the basal forebrain and projecting to the cortex and hippocampus releases acetylcholine in the cortex and hippocampus, which results in vasodilation and an increase in regional cerebral blood flow (rCBF) in the cortex and hippocampus. The augmentation of rCBF is independent of both systemic blood pressure and regional metabolism. The intracerebral cholinergic fibers are able to act as autonomic nerve fibers for the regulation of cortical and hippocampal blood flow.

Regulation of regional cerebral blood flow by cholinergic fibers originating in the basal forebrain.

The intracranial neural vasodilative system of cholinergic fibers projecting from the basal forebrain to the cortex was discovered by Biesold, Inanami, Sato and Sato (Biesold, D., Inanami, O., Sato, A., Sato, Y., 1989. Stimulation of the nucleus basalis of Meynert increases cerebral cortical blood flow in rats. Neurosci. Lett. 98, 39–44) using laser Doppler flowmetry in anesthetized rats. This cholinergic vasodilative system, which operates by increasing extracellular ACh release, relies upon activation of both muscarinic and nicotinic cholinergic receptors in the parenchyma of the cortex. Further, the involvement of nitric oxide in this cholinergic vasodilation, indicates the necessity to this system of neurons, which contain nitric oxide synthase. The increase in cortical blood flow elicited by this cholinergic vasodilative system is independent of systemic blood pressure and is not coupled to cortical metabolic rates. This cholinergic vasodilative system may be activated by somatic afferent stimulation. Most of the data presented here were obtained in anesthetized animals.

Sympathetic and parasympathetic regulation of the uterine blood flow and contraction in the rat

The effects of electrical stimulation of hypogastric sympathetic and pelvic parasympathetic nerves on uterine blood flow and contraction in anesthetized female non-pregnant normal cycling rats were examined. Electrical stimulation of the efferent pelvic nerve with supramaximal intensity induced marked increase of uterine blood flow accompanied by uterine contraction. On the other hand, the stimulation of efferent hypogastric nerve caused decrease of uterine blood flow accompanied by uterine contraction. These responses could only be elicited with stimulus intensity above the threshold for unmyelinated C fibers in both the hypogastric and pelvic nerves. Intravenous administration of atropine (0.5 mg/kg) totally blocked the response of uterine contraction elicited by pelvic and hypogastric nerve stimulation and also the increase of blood flow induced by pelvic nerve stimulation. Intravenous administration of phenoxybenzamine (0.5 mg/kg) blocked the decreased response of uterine blood flow induced by hypogastric nerve stimulation. It was concluded that uterine blood flow and contraction were regulated by both the parasympathetic and sympathetic nerves, but in different manners; blood flow is regulated reciprocally (1) by parasympathetic vasodilators mainly via activation of muscarinic cholinergic receptors, and (2) by sympathetic vasoconstrictors via activation of alpha-adrenergic receptors; contraction is produced by activation of both parasympathetic and sympathetic nerves via muscarinic cholinergic receptors.

Reflex modulation of visceral functions by acupuncture-like stimulation in anesthetized rats

Abstract Our recent studies of the neural mechanisms of the reflex effects on visceral functions of acupuncture-like stimulation applied to the skin and underlying muscle by twisting a needle in anesthetized rats are reviewed. Gastric motility was inhibited by acupuncture-like stimulation of the abdominal areas and facilitated by limb stimulation. The rhythmic micturition contractions of the urinary bladder were inhibited by stimulation of the perineal area. Responses of sympathoadrenal medullary function to acupuncture-like stimulation were inconsistent. Blood pressure responses were inconsistent, but in a deep anesthetized condition, acupuncture-like stimulation applied to the hindlimb muscles caused a decrease in blood pressure. Each of the responses observed was a reflex response whose afferent pathways consisted of cutaneous and muscle afferent nerves and efferent pathways consisted of the autonomic efferent nerves. The reflex center was in the central nervous system (CNS). Some of these reflexes were characterized by segmental organization and others by nonsegmental organization. The spinal cord was essential for the segmental reflexes, while the supraspinal cord was essential for the nonsegmental generalized reflexes. The generalized reflex was elicited by stimulation to various spinal segments, particularly by stimulation to limbs.

Regulation of cerebral cortical blood flow by the basal forebrain cholinergic fibers and aging.

This article reviews the study of neural vasodilator mechanisms of the cerebral cortex by basal forebrain cholinergic nerve fibers and their age-related function in rats. During the last decade, we have demonstrated a neural regulatory system of cerebral blood flow in rats involving intracerebral cholinergic vasodilator nerve fibers originating in the basal forebrain and projecting to the cerebral cortex. Activation of these cholinergic vasodilator fibers results in the release of acetylcholine (ACh) within the cortex, activation of both nicotinic and muscarinic ACh receptors, and vasodilatation without coupling to glucose metabolic rates. This cholinergic vasodilator system has been shown to decline with age in rats mainly due to age-related declines of nicotinic ACh receptor activity. However, muscarinic ACh receptor activity and the release of ACh into the extracellular space in the cortex are well maintained during aging. The present age-related decline of the intracerebral cholinergic vasodilator system found in rats seems to affect cognitive function during aging, although this cholinergic vasodilator system has not yet been demonstrated in humans.

Neural mechanism of pupillary dilation elicited by electro-acupuncture stimulation in anesthetized rats

The neural mechanisms to reflex dilation elicited by electro-acupuncture stimulation were investigated in anesthetized rats. Two needles, with 160 microns diameter and about 5 mm apart, were inserted into the skin and underlying muscle of a hindpaw. Repetitive 20 Hz, 0.5 ms electrical pulses at various intensities were used for stimulation for 30s. The pupil size was magnified about 44 times via a microscope and was continuously recorded on a videotape. Electro-acupuncture stimulation at more than 0.5 up to 6 mA induced stimulus intensity-dependent pupil dilation. These responses were abolished by the severance of the sciatic and saphenous nerve of the stimulated hindlimb. Compound action potentials were recorded from the distal cut end of the tibial of a saphenous nerve following electro-acupuncture stimulation of the hindpaw. The mean threshold of the compound action potentials of the myelinated fibers in saphenous nerves was 0.18 mA, while that of unmyelinated fibers was 3.0 mA. The mean threshold of the compound action potentials of the myelinated fibers in the tibial nerve was 0.20 mA of unmyelinated fibers was 3.3 mA. Severance of bilateral trunks did not affect the response, while severance of the third cranial nerves abolished the responses. In conclusion, electro-acupuncture stimulation applied to the hindpaws of the anesthetized rats induced excitation of myelinated or of both myelinated and unmyelinated afferent fibers of the tibial and saphenous nerve, and involved a reflex response of pupil dilation through the third cranial parasympathetic efferent nerve.

The influence of afferent inputs from skin and viscera on the activity of the bladder and the skeletal muscle surrounding the urethra in the rat.

(1) Somato-visceral and viscero-visceral reflex interactions have been studied in the bladder branches of the pelvic nerve and in the electromyographic (EMG) activity of the periurethral skeletal muscles of the anesthetized rat, and by observations of changes in bladder motility. (2) Slow distensions of the bladder caused some elevation of intravesical pressure, and culminated in a micturition contraction. Periurethral EMG activity increased gradually during the bladder distension, and showed an oscillatory marked increase during the bladder contraction. There was a small increase in pelvic nerve efferent activity during slow distension, and there was a substantial increase before, or at the start, of a micturition contraction. (3) Oscillatory bursting activity occurred in recordings of the EMG activity from periurethral skeletal muscle during the rising phase of micturition contraction; this was particularly so during the most rapid rise in intravesical pressure, and periods of electrical silence lasting 80-270 ms alternated with bursts of activity in the periurethral EMG. (4) In the present experiments, the switching mechanism activated by pelvic afferent signals related to intravesical pressure reversed the behavior of a number of reflex pathways. When the bladder pressure was low, nociceptive pinching of the perineal skin usually caused bladder contraction and a rise in pelvic nerve efferent activity and in periurethral EMG activity. When the bladder was full, micturition contractions were present and reduced in size and frequency by pinching of the perineal skin. The pelvic nerve efferent activity was correspondingly reduced, while the EMG activity increased during and following the nociceptive stimulus. Cooling the scrotal skin with ice also decreased the frequency of bladder contractions. (5) When the bladder pressure was low, distension of the anus and colon increased periurethral EMG activity, but did not affect bladder tone. However, when the bladder was full, these stimuli reduced the size and frequency of bladder contractions, associated with a reduction in the pelvic nerve efferent activity. There was usually a simultaneous reduction in the EMG activity in periurethral muscles. Similar results were obtained during distension of the seminal vesicles or vagina, or following injection of 20-60 microliters of saline into the lumen of the vas deferens. Reversal of the responses at extremes of intravesical pressure was observed in every case. (6) Following spinal transection at the upper cervical or thoracic level, micturition contractions were absent at high bladder volumes. However the effects described when the neuraxis was intact and the bladder pressure was low were still observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood flow in the sciatic nerve is regulated by vasoconstrictive and vasodilative nerve fibers originating from the ventral and dorsal roots of the spinal nerves

Anesthetized rats were subjected to repetitive electrical stimulation of either the ventral or dorsal root of the spinal nerves between the 11th thoracic and 2nd sacral spinal segments. The response of nerve blood flow (NBF) in the sciatic nerve was examined using laser Doppler flowmetry. For all nerve fibers stimulation was for a 10-30-s period at a supramaximal intensity. (1) Stimulation of the T11-L1 ventral roots produced an increase in mean arterial pressure (MAP) and a biphasic NBF response was comprised of an initial increase and a subsequent decrease. The initial increase was a passive vasodilation due to the increase in MAP, while the following decrease in NBF resulted from active vasoconstriction of the vasa nervorum due to the activation of sympathetic nerves innervating the sciatic vasa nervorum. (2) Stimulation of the ventral root of the L6 segment produced an increase in NBF, even though MAP decreased. This increase in NBF was apparently mediated by activation of parasympathetic cholinergic vasodilators, because the response was abolished by i.v. injection of atropine, a muscarinic cholinergic receptor antagonist. (3) Stimulation of the dorsal roots between the L3 and S1 segments produced an increase in NBF, independent of changes in MAP. This increase in NBF appeared to be mediated by activation of a calcitonin gene-related peptide (CGRP) containing afferent fibers innervating the vasa nervorum, because the response was abolished by topical application of hCGRP (8-37), a CGRP receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)