维生素E增强雷米普利的抗高血压心肌肥厚作用及其可能机制

目的：探讨维生素Ｅ和雷米普利对大鼠高血压心肌肥厚的作用与机制。方法：建立腹主动脉缩窄性大鼠高血压心肌肥厚模型，采和低剂量ｒａｍｉｐｌａｔ，ＶｉｔＥ和一氧化氮合酶抑制剂Ｎ－Ｌ－ａｒｇｉｎｉｎｅ喂养大鼠，８周后观察大鼠血压，左室／体重比值，左室心肌组织超氧化物歧化酶活性和离体主动脉内皮依赖性舒张功能。     

An investigation into mechanisms of reflex reinforcement by the Jendrassik manoeuvre

Tendon jerk and H-reflexes are both potentiated by the Jendrassik manoeuvre, but the mechanism of potentiation remains uncertain. We investigated several possibilities in human subjects. Evidence for fusimotor activation during the Jendrassik manoeuvre was sought by recording the tendon jerk reflex as surface EMG in triceps surae after the muscles had been conditioned to leave their spindles in a slack, insensitive state. Interposing a Jendrassik manoeuvre between conditioning and the test reflex should have increased reflex amplitude by restoring spindle sensitivity, but this was not the case. In humans, a close synergist of the triceps surae is the quadriceps. A possible presynaptic disinhibitory mechanism was investigated by testing the effect of a Jendrassik manoeuvre on facilitation of the soleus H-reflex produced by a quadriceps afferent volley. The Jendrassik manoeuvre failed to increase facilitation, contrary to what would be expected if it reduced the level of tonic presynaptic inhibition; the assumption being that the inhibition acts on both homonymous and synergist afferent terminals. The Jendrassik manoeuvre did not increase the level of ongoing EMG in the soleus during a weak voluntary contraction, indicating that it does not operate by direct facilitation of motoneurones. There was found to be less potentiation of soleus tendon jerk and H-reflexes by the Jendrassik manoeuvre under conditions when spindles in the soleus were likely to have a high resting discharge rate. A remaining possibility is discussed: that the Jendrassik manoeuvre operates by modulation of oligosynaptic pathways that may contribute to the largely monosynaptic reflex response. These experiments demonstrate, with new, more sensitive methods than previously used, that neither is the fusimotor system involved in reinforcement nor are direct excitatory or presynaptic disinhibitory effects on motoneurones. While this confirms the previously prevailing view, none of the lingering uncertainties associated with the methods used now remains.     

A pharmacological analysis of the neuronal circuitry involved in distension-evoked enteric excitatory reflex

Isolated segments of guinea-pig small intestine were set up in a partitioned bath to study the enteric excitatory reflex evoked by distension. The gut was distended by a rubber balloon inserted at the aboral end and contractions of the circular muscle were recorded at the oral end. The oral and aboral ends of the gut were separated by an intermediate compartment of the bath. Inflation of the intraluminal balloon with 0.075-0.35 ml water elicited reproducible and distension-dependent contraction. This enteric orally directed (ascending) excitatory reflex was abolished by tetrodotoxin irrespective of the compartment in which it was applied. Hyoscine (0.3 microM) almost abolished the enteric excitatory reflex when it was applied to the oral compartment. This indicates that the transmission from the final motor neurons to the circular muscle is mainly cholinergic, acting via muscarinic receptors. Hyoscine had no effect on the enteric excitatory reflex when added to the intermediate compartment. When hyoscine was added to the aboral compartment, it decreased the enteric excitatory reflex elicited by low distension stimuli to 70% of control and decreased the enteric excitatory reflex elicited by higher distension stimuli to 95% of control. This indicates that ganglionic transmission involving muscarinic receptors at the site of distension in the aboral bath contributes to the enteric excitatory reflex. Hexamethonium (100 microm) greatly depressed the enteric excitatory reflex when applied to any compartment indicating that nicotinic transmission is most important in the afferent, intermediate and efferent components of the reflex and that the reflex pathway involves a polysynaptic chain of cholinergic interneurons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Different mechanisms involved in supraspinal and spinal reflex regulation of phrenic activity through chest movements

The coordination of breathing activity with chest movements was compared in the same decorticate rabbit preparations prior to and after a transection at the C2 spinal level. Pharmacological activation was induced with a combination of nialamide and DOPA in the latter situation. The preparation was curarized and chest inflations and deflations were induced by a respirator whose parameters could be modified. In decorticate preparations, phrenic activity was coordinated 1:1 with the respirator period over a large range of imposed periods. Beyond the extreme values a new coupling was achieved with a ratio of either 1:2 or 2:1. Throughout the range of 1:1 coordination, phrenic bursting always happened at a preferred time in the respirator period, although this time differed for the various imposed periods. This coordinated activity required vagal inputs. After spinal transection the phrenic nerves were totally silent; DOPA administration allowed rhythmic activity to develop. In some preparations, phrenic bursts were coordinated 1:1 with the respirator period and remained so for all the imposed periods: the phase of these phrenic discharges relative to the respirator cycle was kept unchanged for the different periods. In addition, there was a modulation of amplitude superimposed on this 1:1 coupling. These spinal phrenic bursts were generally suppressed when the respirator was turned off. From these results, the coordination of phrenic activity with the respirator rate appears to be produced by different mechanisms in the decorticate and in the spinal preparations. In the decorticate animal the periodic vagal inflow reset the activity of the medullary inspiratory generator and entrains it at its own rate. The coordination observed in the spinal preparation results from a periodic peripheral activation of premotoneuronal or motoneural phrenic elements during inflation. If the central bursts provided by the spinal "respiration" generator can fire phrenic motoneurons above threshold, their timing is not dependent on the peripheral inflow; when the motoneurons are fired below threshold by these central inputs, they are probably summing together the central and peripheral excitations, which could account for the amplitude modulation of the coordinated phrenic bursts of pure reflex origin. Possible afferent pathways are discussed.     

The internal anal sphincter in the cat: a study of nervous mechanisms affecting tone and reflex activity

1. Smooth muscle activities in rectum and internal anal sphincter have been recorded using intraluminal balloons.2. Reflex activation of the sphincter, caused by distension of the rectum, has been assessed before and after various combinations of blocking drugs.3. Responses to stimulation of hypogastric or sacral nerves, or to the administration of drugs with autonomic actions have been tested before and after various combinations of blocking drugs.4. Results indicate that the tone of the internal anal sphincter is influenced by a number of neural mechanisms. These include motor pathways involving both alpha-adrenergic and cholinergic mechanisms and inhibitory pathways involving both beta-adrenergic and non-adrenergic non-cholinergic mechanisms.5. Cholinergic contractions of the sphincter were converted to relaxations after alpha-adrenergic blockade. This indicates that the contractions are an indirect effect operating through an adrenergic reflex. Cholinergic relaxations may also be indirect and operate through reflex inhibition secondary to rectal contractions.6. Sphincteric motor activity is controlled largely through alpha-adrenergic mechanisms by adrenergic nerves acting directly on the muscle. beta-Adrenergic inhibitory mechanisms are thought to operate indirectly via ganglia.7. The over-all control of the sphincter is by complex reflex mechanisms involving numerous pathways and the activity of the sphincter at any one time is determined by the net balance between motor and inhibitory influences.8. Sacral nerve stimulation indicated that it contains cholinergic nerves to the rectum, non-adrenergic non-cholinergic inhibitory axons to the sphincter and variable numbers of adrenergic axons to the sphincter.9. Responses of the sphincter to drugs and nerve stimulation were often variable, as has been described many times in the literature. It is considered that this is due to complex combinations of indirect reflex effects, secondary to activation of structures outside the sphincter, operating with or against direct effects on the sphincter itself.     

Spinal mechanisms of the functional stretch reflex

Summary A sudden and rapid angular displacement of the limb evokes, in human and monkey subjects, a segmented pattern of electromyographic activity in muscles which are stretched. While the first segment is acknowledged to represent a tendon jerk, it has been proposed that the second segment, occurring with a shorter latency than a reaction time, is mediated by a transcortical loop. The present experiments were conducted in cats to determine the properties of muscle responses to torque perturbations analogous to those used in the monkey, and to determine if the integrity of supraspinal pathways is required for the individual response segments to occur.Torque perturbations which flexed the forearm evoked a segmented response in the electromyogram of the cat triceps muscle. This response typically consisted of three early segments with latencies of 10, 30 and 60 msec which were similar to the M1, M2, and M3 segments described in the monkey. The M3 and occasionally M2 components were depressed when the cat followed rather than resisted the perturbation. A torque pulse of 10 msec duration was sufficient to elicit a near maximal M1 response while torque pulses in excess of 20 msec were required to evoke the M2 response.To determine if any of these components required mediation by the cerebral cortex, experiments were conducted in decerebrate and spinal cats. Similar torque perturbations produced segmented electromyographic responses in the triceps muscles which were indistinguishable in their timing from those observed in intact cats. The torque required to produce the segmented responses was comparable as well. All three segments were dependent upon the activation of receptors in the homonymous muscle and did not require cutaneous input. These observations show that receptor properties and/or spinal mechanisms involved in the stretch reflex are sufficient to produce a segmented response similar to that observed in intact animals.     

Influence of mannitol-induced reduction in CSF Na on nervous and endocrine mechanisms involved in the control of fluid balance

Infusions (20 μl/min) of isotonic (0.27 M) and hypertonic (0.7 M) mannitol dissolved in Na-free artificial CSF were made for 1 h. into the lateral cerebral ventricle (IVT) of conscious water-replete sheep. The IVT infusion of both 0.27 M and 0.7 M mannitol induced a water-diuresis. Samples of CSF were collected prior to, and 5, 35, 65 and 125 min after the end of the infusion. These consistently showed a reduction in CSF [Na], while CSF osmolality remained unchanged after 0.27 M mannitol, and was considerably increased after 0.7 M mannitol. In the 44 h dehydrated sheep IVT infusion of 0.7 mannitol in Na-free artificial CSF was made for 6 h. The water deprivation as such caused a marked increase in plasma and CSF [Na] and osmolality. The 6 h IVT infusion of hypertonic mannitol further increased the CSF osmolality, while CSF [Na] decreased and reached a value below the normal for water-replete animals. The infusion also induced a fall in plasma ADH resulting in a water-diuresis, and extinguished the thirst of the dehydrated sheep. Furthermore, the infusion markedly reduced renal sodium excretion without causing any substantial change in blood aldosterone, in spite of the fact that there was a conspicuous increase in plasma renin concentration. The study supports the view that sodium sensitive receptors close to the cerebral ventricular system participate in the regulation of ADH secretion, water intake, renin release, and renal sodium excretion.     

Neural mechanisms underlying the clasp-knife reflex in the cat. I. Characteristics of the reflex

1. The goal of this study was to characterize the clasp-knife reflex by the use of stretch and isometric contraction of ankle extensor and flexor muscles in decerebrated cats with bilateral dorsal hemisections of their spinal cords at segment T12. 2. Stretch of an extensor muscle evoked inhibition in both homonymous and synergistic extensor muscles. The similarities between homonymous and synergistic inhibition suggest that similar neural mechanisms were responsible. 3. Homonymous and synergistic clasp-knife inhibition showed several characteristic features: 1) inhibition was evoked only by large stretches that produced significant muscle force. Short stretches that did not produce large forces evoked only excitation; 2) the magnitude of clasp-knife inhibition increased with increasing initial motor output, as reflected in the level of rectified EMG; 3) the time course of reflex inhibition evoked by ramp-and-hold stretch was characterized by segmentation of EMG during ramp stretch, dynamic overshoot of inhibition at the end-of-ramp stretch, and slow but usually complete decay of inhibition during maintained stretch; 4) inhibition persisted beyond the termination of stretch, and 5) inhibition showed adaptation to repeated stretch. 4. Isometric contraction of the soleus or medial gastrocnemius, produced by electrical stimulation of the muscle nerve, also evoked powerful synergistic-reflex inhibition via similar mechanisms as stretch-evoked, clasp-knife inhibition. Stretch evoked a greater degree of inhibition than did contraction, indicating that receptors responsive to both stretch and contraction contribute to clasp-knife inhibition. 5. The reflex effects produced by stretching the soleus or medial gastrocnemius were not confined to the homonymous and close synergistic muscles. Extensor muscles were inhibited and flexor muscles were excited throughout the hindlimb, which paralleled the pattern of a flexion-withdrawal reflex evoked by cutaneous stimulation. 6. Stretch of a flexor muscle, the tibialis anterior, evoked the same spatial pattern and time course of reflex action as stretch of an extensor muscle--inhibition of extensor muscles and excitation of flexor muscles throughout the hindlimb, including homonymous excitation of the tibialis anterior. 7. We conclude that neither Golgi tendon organs nor secondary spindle afferents are likely to contribute significantly to clasp-knife inhibition because their responses to stretch and isometric contraction differ from the reflex actions evoked by stretch and contraction.(ABSTRACT TRUNCATED AT 400 WORDS)