LACK OF SYMPATHETIC AUGMENTATION IN RESPONSE TO INTRAVENOUS LOAD OF GLUCOSE IN RABBITS

1. We investigated a link between sympathetic nervous function and carbohydrate metabolism by measuring renal sympathetic nerve activity in response to intravenous load of glucose in alpha-chloralose-urethane anaesthetized rabbits. 2. Intravenous infusion of a 25% glucose solution (0.5 g/kg) over 3 min caused a transient increase in arterial blood pressure and a decrease in renal sympathetic nerve activity. Thereafter, these parameters were restored and remained around preload levels while plasma glucose and insulin concentrations were still elevated. 3. Equimolar mannitol solution produced similar patterns of change in blood pressure and nerve activity without an elevation of plasma glucose and insulin levels. 4. The transient changes in blood pressure and renal nerve activity could be attributed to acute hypervolaemia indicated by similar changes in plasma osmolality and haematocrits in the two groups of treatment. 5. The present study did not support a close relationship between carbohydrate metabolism and the sympathetic nervous system regulating cardiovascular function.     

RENAL SYMPATHETIC NERVE ACTIVITY MEASURED BY NOREPINEPHRINE SPILLOVER RATE IN RESPONSE TO CHANGES IN BLOOD PRESSURE IN CONSCIOUS RABBITS

1. Renal sympathetic nerve activity (RSNA) in response to changes in mean arterial pressure (MAP) was examined by measuring renal norepinephrine (NE) spillover rate in conscious rabbits. 2. A chronic renal vein catheter was implanted for sampling renal venous blood without stress in conscious animals. 3. RSNA estimated by renal NE spillover rate significantly increased in response to moderate falls in MAP produced by sodium nitroprusside (SNP) infusion and decreased in response to moderate rises in MAP produced by phenylephrine (PE) infusion. 4. The NE spillover method is sufficiently sensitive to detect responses of RSNA to physiological stimuli in conscious rabbits.     

LONG-TERM INCREASES IN RENAL SYMPATHETIC NERVE ACTIVITY AND HYPERTENSION

1. Essential hypertensive patients have been characterized by increased sympathetic nerve activity, increased peripheral vascular tone, decreased plasma volume and normal cardiac output when compared with normotensive subjects. Bilateral renal denervation reduces the magnitude or delays the onset of the blood pressure response in numerous models of experimental hypertension regardless of the aetiology of the elevation in arterial pressure. 2. Using a servocontrolled intrarenal infusion system, we have elevated intrarenal noradrenaline concentration via intermittent renal artery infusion without decreasing renal blood flow as a method of simulating selective elevation of renal sympathetic outflow. 3. Chronic intrarenal adrenergic stimulation increased arterial pressure within 24 h and this hypertension persisted for 28 consecutive days. The elevated arterial pressure was not associated with sustained increases in plasma renin activity, aldosterone, circulating catecholamines, arginine vasopressin or significant renal vasoconstriction. Urinary sodium excretion was chronically elevated and the dogs remained in negative sodium balance for the duration of the intrarenal noradrenaline infusion. 4. After 2 weeks of elevated intrarenal neurotransmitter coupled with hypertension, renal vascular reactivity to further adrenergic stimulation was significantly increased because the hypertension was maintained during continual reductions in the daily dosage of neurotransmitter allowed to be infused by the servocontroller. After only 28 days of noradrenaline infusion, renal vascular hypertrophy developed in vessels from 150–300 μm. 5. We conclude that selective and intermittent increases in intrarenal adrenergic neurotransmitter are sufficient to elicit chronic hypertension in the absence of volume expansion. This intrarenal neuroadrenergic hypertension is closely associated with the haemodynamic parameters which characterize a major subset of human essential hypertensives.     

VASOCONSTRICTION IN THE RENAL VASCULAR BED DURING EXERCISE: STUDIES IN CONTROL AND HEART FAILURE RABBITS

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.     

RESPIRATORY ALTERATIONS WITH INTRAPERICARDIAL PROCAINE IN THE CONSCIOUS RABBIT

• 1 Intrapericardial procaine, used to produce cardiac nerve blockade in both conscious and anaesthetized animals, has been reported to also produce changes in respiration. This study systematically investigated the effects of two doses of intrapericardial procaine on respiration in the conscious rabbit.
• 2 Rabbits were pre-instrumented with a chronic diaphragm electromyogram (dEMG) recording electrode and intrapericardial catheter. Arterial pressure, heart rate, dEMG and respiratory excursions (recorded with a pneumograph) were monitored in the conscious rabbit before and after intrapericardial and intravenous infusion of 2 and 5% procaine. Efficacy of cardiac nerve blockade was tested by intravenous infusion of phenyl biguanide. Arterial blood gases were determined at rest and during changes in respiration.
• 3 Following a low dose of intrapericardial procaine (12 mg), dEMG and respiratory excursions increased (65 ± 13 and 65 ± 13%, respectively) with no change in breathing frequency or arterial blood gases. Following a high dose of intrapericardial procaine (30 mg), four of six animals exhibited a similar response. However, four of the six rabbits also exhibited a second type of response pattern characterized by a further increase in respiratory efforts (65 ± 13%), abolition of dEMG, and a mild hypoxaemia.
• 4 Intravenous infusion of a low dose of procaine was without effect, whereas intravenous infusion of a high dose of procaine produced minor behavioural responses.
• 5 In four additional anaesthetized rabbits, it was demonstrated that high doses of intrapericardial procaine anaesthetized the phrenic nerve to produce the observed alterations in respiration.
• 6 We conclude that if intrapericardial procaine is used to block cardiac nerves in conscious rabbits, it should be used in a low concentration and at the lowest possible total dose to avoid complications due to changes in respiration.

     

重组牛碱性成纤维细胞生长因子治疗视神经损伤的药理学研究

目的：研究重组牛碱性成纤维细胞生长因子（rbFGF)在视神经损伤修复中的作用。方法：视神经部分损伤后，球后分别注射生理盐水、维生素B12、bFGF，伤后4周测量闪光视神经诱发电位（F－VEP），进行轴突定量、视网膜神经节细胞（RGCs)定量以及RGCs凋亡的检测，观察视神经损伤修复情况。结果：伤后4周时生理盐水维生素B12组对照刺激无反应，bFGF组F－VEP接近正常，800U、1600U和2400UbFGF对RGCs挽救率分别为24．5％、27．3％、28．5％，800U、1600U和2400UbEGF组未发生演变的轴突数分别是损伤末治疗组的2．03、2．43、2．31倍。流式细胞仪检测结果显示，bFGF治疗7d后，RGCs凋亡率显著减少。结论：bFGF可挽救视网膜神经节细胞的存活，减少轴突溃变，有抗凋亡作用，对视神经损伤有显著地促功能修复作用。     

FUNCTIONAL SIGNIFICANCE OF THE 10 Hz RHYTHMIC DISCHARGES IN SYMPATHETIC NERVES

1. By measuring renal vascular conductance in anaesthetized and immobilized rabbits, the functional significance of the 10 Hz rhythmic discharges in the sympathetic nerves was assessed by electrical stimulation of the renal nerve. This stimulation mimicked the intermittently occurring 10 Hz rhythmic discharges. 2. Comparison of high-frequency (10-20 Hz) intermittent electrical stimulation with continuous low-frequency (5 Hz) stimulation showed that the intermittent high-frequency stimulation evoked faster (smaller time constant) and larger responses of the renal vascular conductance if the total number of stimulus pulses was the same. 3. Therefore, the intermittently occurring 10 Hz rhythmic discharges in the sympathetic nerve produces faster and larger effects on peripheral organs than effects produced by continuous discharges if the number of spikes is equal.     

INVOLVEMENT OF NON-NMDA AND NMDA RECEPTORS IN GLUTAMATE-INDUCED PRESSOR OR DEPRESSOR RESPONSES OF THE PONS AND MEDULLA

1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito-neally with urethane (400 mg/kg) and a-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50–100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.     

CHAOTIC CHARACTERISTICS OF RENAL NERVE PEAK INTERVAL SEQUENCE IN NORMOTENSIVE AND HYPERTENSIVE RATS

1. The use of non-linear dynamic analysis for the measurement of control processes in low-dimensional signals, for example, blood pressure and heart rate variability, are well established and accepted. However, the application of these analytical techniques to a high-dimensional signal, such as renal sympathetic nerve activity (RSNA), has not been validated. 2. The present study set out to develop an approach whereby the high-dimensional signal of RSNA was reduced to a low-dimensional one by extracting the peak interval sequence (PIS), using Cluster analysis, in order to allow the use of non-linear dynamics analysis. Brachial nerves were electrically stimulated (1.6 Hz, 0.2 ms, 15 V) to elicit a sympatho-excitation in groups of anaesthetized normotensive Wistar and stroke-sprone spontaneously hypertensive rats (SHRSP). 3. It was found that, under basal conditions, the correlation dimension, D₂, was stable over a range of embedding dimensions from 12 to 25. Moreover, the largest Lyapunov exponent had a small positive value that was also stable over these embedding dimensions. These values showed that the signal was of low dimensionality and that chaos was present. 4. In Wistar rats, brachial nerve stimulation significantly (P<0.05-0.001) increased blood pressure (by 25%), heart rate (by 5%) and RSNA (by 200%), which was associated with significant (P<0.05) reductions in the correlation dimension D₂ and the largest Lyapunov exponent of the PIS generated from the renal nerve signal. In contrast, in SHRSP, there were similar increases in blood pressure, heart rate and RSNA in response to brachial nerve stimulation, but neither the correlation dimension nor largest Lyapunov exponent was altered. 5. These findings demonstrate that by extracting the PIS from the renal sympathetic nerve signal, the application of non-linear chaos analysis makes it possible to distinguish differences in the pattern of refiexly induced excitation in sympathetic traffic to the kidney in the pathophysiological state of hypertension. Whether this applies to sympathetic outflow to other organs and tissues remains to be investigated.     

VASOPRESSIN COMPENSATES FOR ACUTE LOSS OF SYMPATHETIC PRESSOR TONE IN SPONTANEOUSLY HYPERTENSIVE RATS

1. The aim of this study was to examine the pressor response of vasopressin (AVP) to an acute fall in blood pressure induced by ganglion blockade. 2. Aortic catheters were implanted in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP), normotensive Wistar-Kyoto (WKY), black-hooded Wistar (BHW) and Sprague-Dawley (SD) rats, aged 5–7 weeks and 7–9 months, for direct measurement of mean arterial pressure (MAP) under conscious, resting conditions. The ganglion blocking agent pentolinium was administered intra-arterially, followed by an AVP receptor antagonist specific for the pressor effect of AVP. The basal level of MAP attained with each drug was recorded. 3. In the adult SHR and SHRSP with established hypertension, acute ganglion blockade caused MAP to fall to a similar extent as in WKY, suggesting that the level of sympathetic pressor tone was similar in all three strains. Administration of the AVP antagonist alone did not affect resting MAP. During ganglion blockade, however, it caused a further reduction of MAP in WKY, SHR and SHRSP, the magnitude of which was greater in the hypertensive strains. After both drugs, the total fall in MAP and the residual MAP were significantly greater in the hypertensive rats. 4. In young rats, AVP had little effect on MAP, even during ganglion blockade. The residual level of MAP after both drugs was greater in the hypertensive strains. 5. The extent to which AVP can compensate for an acute fall in MAP increases with age and the development of hypertension. This tends to mask the loss of sympathetic mediated pressor tone after ganglion blockade. By preventing this compensation we have shown that the sympathetically mediated component of blood pressure is elevated in SHRSP with established hypertension.     

ENDOTHELIN-1 ENHANCES VASOCONSTRICTOR RESPONSES TO SYMPATHETIC NERVE STIMULATION AND NORADRENALINE IN THE RABBIT EAR ARTERY

1. In rabbit isolated perfused ear arteries denuded of endothelium, a low concentration of endothelin-1 (0.1 nmol/L) that had no direct vasoconstrictor action produced slowly developing enhancements of vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation. The enhancements reached maximal levels after 60 min of exposure to endothelin-1. 2. A higher concentration of endothelin-1 (1 nmol/L), which produced a slow-developing increase in perfusion pressure of 70 mmHg over the course of 1 h, significantly enhanced vasoconstrictor responses to sympathetic nerve stimulation for the first 30 min, after which there was no significant enhancement. Responses to noradrenaline were not enhanced by 1 nmol/L endothelin-1. 3. The enhancing effect of low concentrations of endothelin-1 on vasoconstrictor responses to sympathetic nerve stimulation and noradrenaline may play a physiological role in modulating vasomotor function.     

骨间前神经旋前方肌支转位修复鱼际肌支和尺神经深支的解剖学观察和临床应用

目的了解有关应用骨间前神经旋前方肌支转位修复正中神经鱼际肌支和尺神经深支的解剖,总结应用此方法的临床效果。方法观察6具成人上肢标本,测量其旋前方肌支、正中神经鱼际肌支和尺神经深支的横径,以及正中神经鱼际肌支起始处、尺神经深支起始处至旋前方肌上缘的距离。1996年4月～1997年3月,临床应用5例。旋前方肌支转位修复陈旧性尺神经损伤3例,陈旧性正中神经损伤1例,急性正中神经损伤1例,其中3例需游离神经移植。结果骨间前神经旋前方肌支在旋前方肌上缘处、正中神经鱼际肌支起始处、尺神经深支起始处,神经干横径分别为1.3～1.9、1.5～2.3、1.8～2.3mm。正中神经鱼际肌支起始处、尺神经深支起始处至旋前方肌上缘的距离分别是75.2～84.8mm、53.5～74.0mm。临床应用经12～23个月随访,4例手内在肌功能恢复M3～M4级,1例未见恢复。结论骨间前神经旋前方肌支转位修复正中神经鱼际肌支和尺神经深支可达到肌支-肌支修复的设想,缩短再生距离和时间,有利于手内在肌的功能恢复。