Facilitation of adrenal sympathetic efferent nerve activity induced by mechanical stimulation of teeth in the rat

The effects of afferent signals from the periodontal mechanoreceptors and muscle spindles of jaw-closing muscles on adrenal nerve activity were examined using anesthetized rats. The adrenal nerve activity increased with pressure stimulation of the teeth and by biting a wooden stick. However, after denervation of the periodontal ligament, the facilitation due to the stick-biting was not observed. These results indicate that periodontal afferents facilitate adrenal nerve activity.     

The action of tyramine on the hypertensive responses induced by sympathetic stimulation in the pithed rat

This study has evaluated the changes in the characteristics of the H-reflex induced by distention of the urinary bladder in patients with complete lesions of the spinal cord. These findings were compared to induced changes in the systolic blood pressure and some degree of correlation was noted. It is well recognised that distention of the urinary bladder can exert a significant influence on the state of both somatic and autonomic reflex activity in spinal man. Although the mode of action of this stimulus has not been fully delineated, it is of some clinical importance since it may intensify muscular spasticity and autonomic hyperreflexia. This study was undertaken to further explore this relationship utilising the H-wave as a measure of segmental reflex activity. When appropriate, the effect of bladder distention on arterial blood pressure was also measured and an attempt made to correlate these observations with the H-wave findings.     

Effects of electrical stimulation of cervical sympathetic trunks on microcirculation in the facial nerve

This study evaluates the circulatory effects of electrical stimulation of the cervical sympathetic trunks on blood flow in the common carotid artery and facial nerve tissue in dogs. Marked increases in arterial pressure and heart rate were observed due to electrical stimulation of the cervical sympathetic trunks, while blood flow volume in the common carotid artery and in the facial nerve tissue decreased markedly. It was assumed that microcirculation of the facial nerve is definitely impaired by electrical stimulation of the cervical sympathetic trunks, and the tonicity of the sympathetic nervous system appears to be a major factor in changes in the microcirculation of the facial nerve. It is well known that impaired circulation in the nutrient vessels of the facial nerve has an important effect on the pathogenesis of facial palsy. The hypertonicity of the sympathetic nervous system is closely involved in the onset of facial palsy.     

Hydralazine: effect on the outflow of noradrenaline and mechanical responses evoked by sympathetic nerve stimulation of the rat tail artery

1 The effects of hydralazine on the vasoconstrictor responses to field stimulation of sympathetic nerves were studied in the isolated proximal segments of the rat tail artery. Vasoconstrictor responses to transmural stimulation were depressed by superfusion of hydrazine (0.3, 3 and 30 muM) in a concentration-dependent manner. The inhibition appeared slowly and was not easily reversed by washing. 2 Hydralazine (30 nM, 0.3 and 3 muM) reduced the stimulation-induced overflow of tritium from proximal and distal segments of the tail artery labelled with [3H]-noradrenaline in a concentration-dependent manner. This phenomenon appeared rapidly and was easily reversed by washing. 3 Theophylline (0.5 mM) did not affect the inhibitory effect of hydralazine on the stimulation-induced tritium efflux from the distal segment of the rat tail artery. 4 The present results indicate that hydralazine has, in addition to its action on vascular smooth muscle, a very marked effect on sympathetic nerve terminals. The mechanism of this presynaptic inhibition appears to be different from the postsynaptic effect, in view of the much shorter delay, the shape of the dose-effect curve, and the lack of interaction with theophylline.     

Suppression of renin secretion in the isolated rat kidney by cycloheximide

Because 1,2:5,6-dianhydrogalactitol (NSC-132313 (DAG; the main conversion reaction product of the treatment of dibromodulcitol by mild akali or human serum) showed considerable antitumor activity in various mouse and rat tumor systems, a phase I study in 50 patients was conducted with five daily iv treatments repeated every 6 weeks. Thrombocytopenia was the dose-limiting toxicity. At a dose of 40 mg/m2/day for 5 days, the median platelet nadir was 31,000/mm3 and occurred on day 20; the plate count returned to normal within 8 days. At the same dose, the median white blood cell (WBC) nadir was 2,300/mm3 also on day 20-, the WBC count returned to normal within 7 days. Anemia, nausea, and vomiting were usually mild to moderate. No renal, hepatic, central nervous system, cardiac, or pulmonary toxicity was identified. Antitumor effects of DAG were observed in patients with renal, bladder, and small-cell lung cancers. An iv dose of 20-30 mg/m2/day for 5 consecutive days, repeated every 5-6 weeks, was recommended for phase II studies.     

Effect of renal sympathetic nerve stimulation on proximal water and sodium reabsorption

The renal responses to sympathetic nerve stimulation were studied in saline-expanded rats. The left kidney was partially denervated by crushing the left greater splanchnic nerve. Then the distal portion of the nerve was stimulated with square wave pulses of 0.5 ms duration, voltage twice threshold, and 1 or 2 Hz frequency while monitoring the compound action potential. Fibers with conduction speeds of 13-17 m-s-1 and of 0.7-1 m-s-1 were identified. Only stimulation of the latter appeared to produce changes in renal Na and water excretion. Whole kidney and individual nephron studies were performed alternating control and nerve stimulation periods. Nerve stimulation produced approximately a 25% reduction of the left kidney urine volume and sodium excretion. Glomerular filtration rate and renal plasma flow remained unchanged. Right kidney Na and water excretion, glomerular filtration rate, and renal plasma flow remained constant. In the left kidney, during nerve stimulation, the tubular fluid to plasma inulin concentration ratio increased significantly in the late proximal tubule. We conclude that the antidiuresis and antinatriuresis seen during sympathetic nerve stimulation were caused by increased sodium and water reabsorption in the proximal tubule, probably mediated by the stimulation of slowly conducting unmyelinated fibers. These responses appeared to be unrelated to systemic or intrarenal hemodynamic changes.     

Effects of moguisteine on the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve in guinea pigs

The study aimed to further demonstrate the peripheral antitussive properties of moguisteine. Firstly, the antitussive effect of moguisteine on the cough reflex induced by inhalation of citric acid aerosol was evaluated in conscious guinea pigs. Secondly, the effects of both moguisteine and codeine on the centrally mediated cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve were investigated in anesthetized guinea pigs. Moguisteine (2.5-10 mg/kg, intravenously, i.v.) reduced the cough reflex induced by 7.5% citric acid aerosol in a dose-dependent manner, with an ED50 value of 0.55 mg/kg. Both i.v. (0.5-4 mg/kg) and intracerebroventricular (i.c.v., 5-20 microg) injection of codeine dose dependently inhibited the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve; the ED50 values were 0.91 mg/kg and 7.90 microg, respectively. The inhibitory effect of codeine (4 mg/kg i.v.) was abolished by pretreatment with naloxone (2 mg/kg intraperitoneally). In contrast to codeine, neither i.v. (4 and 20 mg/kg) nor i.c.v. (20 microg) injection of moguisteine affected the cough reflex. These results suggest that the antitussive effect of codeine is mediated by central opioid mechanisms, whereas the antitussive effect of moguisteine is mediated by peripheral mechanisms.     

Effects of dopamine and alpha-2 adrenoreceptor blockade on L-dopa and cholecystokinin-induced gastroprotection

Dopamine and cholecystokinin have been colocalized in neurons and represent endogenous enteric neurotransmitters. Both peptides possess potent protective actions against gastric injury when given exogenously. This study was undertaken in conscious female rats to test the hypothesis that cholecystokinin may exert its protective actions via release of dopamine. Experiments were designed to ascertain whether L-dopa, a dopamine precursor, could prevent gastric injury with the same degree of efficacy as cholecystokinin and to determine what role alpha-2 adrenoreceptors and dopamine receptors play in mediating the protective actions of these peptides. Intraperitoneal administration of L-dopa (1 to 25 mg/kg) in a dose-dependent manner prevented the type of macroscopic injury to the acid-secreting portion of the stomach that is caused by 1 ml of orogastric acidified ethanol (150 mmol/L hydrochloric acid/50% ethanol), an effect corroborated by histologic examination. Administration of either the alpha-2 adreno-receptor antagonist yohimbine (0.1 to 1.0 mg/kg) or the dopamine receptor antagonist haloperidol (1 to 5 mg/kg) caused a partial reversal of L-dopa-induced protection but not the protective actions of subcutaneous cholecystokinin (100 microg/kg). Simultaneous administration of both receptor antagonists had an additive effect and completely reversed the protective actions of L-dopa. The dopamine precursor L-dopa was just as effective in maintaining the integrity of the gastric epithelium in the face of a damaging insult as the gut peptide cholecystokinin. However, the data indicate that L-dopa initiates its protective actions through activation of both alpha-2 adrenoreceptors and dopamine receptors, whereas the protective effects of cholecystokinin are elicited by means of a different mechanism.     

Bradycardia induced by intravascular versus direct stimulation of the vagus nerve

Ricin is a heterodimeric cytotoxin composed of RTB, a galactose binding lectin, and RTA, an enzymatic N-glycosidase. The toxin is endocytosed, and after intracellular routing, RTA is translocated to the cytoplasm where it inactivates ribosomes resulting in a loss of host cell protein synthesis and cell death. We show for the first time that the cytotoxicity against cultured T cells by several RTA mutants is directly proportional to the enzyme activity of RTA, suggesting this is a reliable system to measure translocation effects. Large discrepancies between cytotoxicity and enzyme action for a given pair of toxins are therefore attributable to differences in cell binding, uptake, or membrane translocation. Fluid phase uptake and cytotoxicity of isolated RTA are essentially identical to that of the single chain toxin PAP. This important finding suggests that RTA, and the A chain of class 2 RIPs in general, has not evolved special translocation signals to complement the increased target cell binding facilitated by RTB. Experiments with the lectin RCA and with ebulin suggest those toxins have diminished cytotoxicity probably mediated by comparative deficiencies in B chain binding. Addition of a KDEL sequence to RTA increases fluid phase uptake, consistent with the notion that transport to the ER is important for cytotoxicity. Fusion of MBP or GST to the amino terminus of RTA has little effect on enzyme action or cytotoxicity. This result is not altered by protease inhibitors, suggesting the fusion proteins are probably not cleaved prior to translocation of the toxic A chain and implying that the toxins can carry large passenger proteins into the cytoplasm, an observation with interesting potential for analytical and therapeutic chemistry.     

Medullary mechanism of the inhibition on renal sympathetic efferent activities by stimulation of the cervical vagal afferent nerve in rabbits

The presence of angiographic evidence of thrombus is generally thought to be a contraindication to coronary stent placement. This report describes four patients in whom angiographic thrombus was lysed using the Dispatch infusion catheter prior to coronary stenting. Urokinase was infused via the Dispatch catheter with resolution of angiographic evidence of thrombus in all cases. No complications were encountered using this technique, and all patients had excellent angiographic results after stenting. We conclude that lysis of intracoronary thrombus using the Dispatch infusion catheter is feasible and appears safe in this small study. Further trials are needed to determine if this technique reduces the acute stent thrombosis rate compared to other techniques for stent deployment in the presence of angiographic evidence of thrombus.     

Cardiac sympathetic nerve stimulation enhances cardiovascular performance during hyperkalaemia in the anaesthetized pig

A total of 74 patients with poor risk AML (median age 36.7 years, range 4.5-60.6) received a single course of a regimen including mitoxantrone (6 mg/m2 intravenous bolus daily, days 1 to 6), etoposide (80 mg/m2 intravenous over 1 h, daily, days 1 to 6) and intermediate-dose Ara-C (1 g/m2 over 6 h, daily days 1 to 6). 28 patients had failed initial remission induction with daunorubicin and conventional doses of Ara-C, 16 patients had secondary AML and 30 patients had relapsed from initial remission (five within six months, 15 over six months and ten after autologous or allogeneic bone marrow transplantation). Overall 41/74 patients (55%) achieved complete remission, 26 (35%) had resistant disease and seven (10%) died of infection during marrow hypoplasia. A 4-day course of the same regimen was given as consolidation to patients in complete remission. Subsequent antileukemic therapy was individualized. Profound myelosuppression and pancytopenia were universal resulting in fever or documented infections in almost 100% of patient; major hemorrhagic complications occurred in 39% of patients. Extrahematologic toxicity was mild to moderate consisting mostly of nausea and vomiting, oral mucositis and transient liver and cardiac dysfunction. We conclude that the MEC combination chemotherapy program seems to be an effective antileukemic regimen for secondary and advanced AML, with acceptable toxicity.     

Effects of inhibitory amino acids on the frequency components in sympathetic nerve discharge

The effects of the GABA antagonist picrotoxin and the glycine antagonist strychnine on the frequency components in sympathetic inferior cardiac nerve activity were observed. Picrotoxin (0.03-1.0 mg/kg) increased power in the 10-Hz component of sympathetic activity and produced a dramatic shift in the rhythm to higher frequencies. Only small changes were noted in the 2- to 6-Hz component. Strychnine produced a small generalized increase in power in both frequency bands in sympathetic activity. These data suggest that GABA may play an important role in the generation and maintenance of the 10-Hz rhythm in sympathetic activity while glycine likely inhibits activity at a site of convergence of the two rhythms in sympathetic activity.     

Effect of sympathetic nerve stimulation on net transvascular movement of fluid in canine adipose tissue

Net transvascular movement of fluid has been studied in the isolated, autoperfused subcutaneous adipose tissue of the dog, during and after sympathetic nerve stimulation (1-15 Hz) and during infusion of 50% glucose i.a. Net fluid movement was calculated as the difference between change in tissue volume and change in blood volume. Tissue volume was measured by plethysmography and blood volume by external monitoring of circulating 131I-albumin. No net fluid movement of statistical significance was found during or after nerve stimulation except during the first minute of stimulation at 15 Hz when a small net absorption (p less than 0.05) was obtained. In contrast, infusion of glucose at 25-75 mOsm/kg H2O produced a dose-dependent net absorption lasting several minutes, amounting maximally to 0.30 ml x min-1 x 100 g-1. The absence of prolonged net absorption in subcutaneous adipose tissue during nerve stimulation as well as the absence of net filtration after stimulation may be explained by an essentially unaltered mean hydrostatic capillary pressure. The results indicate that adipose tissue does not contribute to the fluid homeostasis of the body via sympathetic resetting of the pre-postcapillary resistance ratio. Thus, mobilisation of fluid from the interstitial space in adipose tissue into the blood does not seem to occur by nerve activity.     

Release of somatostatin and its role in the mediation of the anti-inflammatory effect induced by antidromic stimulation of sensory fibres of rat sciatic nerve

1. The effect of antidromic stimulation of the sensory fibres of the sciatic nerve on inflammatory plasma extravasation in various tissues and on cutaneous vasodilatation elicited in distant parts of the body was investigated in rats pretreated with guanethidine (8 mg kg(-1), i.p.) and pipecuronium (200 microg kg(-1), i.v.). 2. Antidromic sciatic nerve stimulation with C-fibre strength (20 V, 0.5 ms) at 5 Hz for 5 min elicited neurogenic inflammation in the innervated area and inhibited by 50.3 +/- 4.67% the development of a subsequent plasma extravasation in response to similar stimulation of the contralateral sciatic nerve. Stimulation at 0.5 Hz for 1 h also evoked local plasma extravasation and inhibited the carrageenin-induced (1%, 100 microl s.c.) cutaneous inflammation by 38.5 +/- 10.0% in the contralateral paw. Excitation at 0.1 Hz for 4 h elicited no local plasma extravasation in the stimulated hindleg but still reduced the carrageenin-induced oedema by 52.1 +/- 9.7% in the paw on the contralateral side. 3. Plasma extravasation in the knee joint in response to carrageenin (2%, 200 microl intra-articular injection) was diminished by 46.1 +/- 12.69% and 40.9 +/- 4.93% when the sciatic nerve was stimulated in the contralateral leg at 0.5 Hz for 1 h or 0.1 Hz for 4 h, respectively. 4. Stimulation of the peripheral stump of the left vagal nerve (20 V, 1 ms, 8 Hz, 10 min) elicited plasma extravasation in the trachea, oesophagus and mediastinal connective tissue in rats pretreated with atropine (2 mg kg(-1), i.v.), guanethidine (8 mg kg(-1), i.p.) and pipecuronium (200 microg kg(-1), i.v.). These responses were inhibited by 37.8 +/- 5.1%, 49.7 +/- 9.9% and 37.6 +/- 4.2%, respectively by antidromic sciatic nerve excitation (5 Hz, 5 min) applied 5 min earlier. 5. Pretreatment with polyclonal somatostatin antiserum (0.5 ml/rat, i.v.) or the selective somatostatin depleting agent cysteamine (280 mg kg(-1), s.c.) prevented the anti-inflammatory effect of sciatic nerve stimulation (5 Hz, 5 min) on a subsequent neurogenic plasma extravasation of the contralateral paw skin. The inhibitory effect of antidromic sciatic nerve excitation on plasma extravasation in response to vagal nerve stimulation was also prevented by somatostatin antiserum pretreatment. 6. Cutaneous blood flow assessment by laser Doppler flowmetry indicated that antidromic vasodilatation induced by sciatic nerve stimulation was not inhibited by excitation of the sciatic nerve of the contralateral leg (1 Hz, 30 min) or by somatostatin (10 microg/rat, i.v.) injection. 7. Plasma levels of somatostatin increased more than 4 fold after stimulation of both sciatic nerves (5 Hz, 5 min) but the stimulus-evoked increase was not observed in cysteamine (280 mg kg(-1), s.c.) pretreated rats. 8. These results suggest that somatostatin released from the activated sensory nerve terminals mediates the systemic anti-inflammatory effect evoked by stimulating the peripheral stump of the sciatic nerve.     

Cortisol stimulation of parathyroid hormone secretion by rat parathyroid glands in organ culture

Addition of cortisol (10(-6) to 10(-8) M) and related glucocorticoid congeners to cultures of rat parathyroid glands stimulated dose-related increases in parathyroid hormone secretion; the addition of deoxycorticosterone or cortexolone was without effect. Cortexolone, however, inhibited the stimulatory activity of cortisol when both were added to the culture medium. This direct stimulatory effect of cortisol on parathyroid gland secretion may account in part for the increased concentration of parathyroid hormone in the serum of cortisol-treated animals.     

Spinal cord segments mediating tonic sympathetic nerve discharge to the kidney in the anesthetized cat

According to anatomical data, preganglionic neurons projecting to the kidney via sympathetic ganglia occupy a wide range of adjacent segments in the thoracolumbar spinal cord, from Th7 to L2. Since, however, the majority of preganglionic neurons is silent at resting states, the active segments indeed transmitting sympathetic activity, at rest, may be different. In the present experiments, the spontaneous sympathetic activity was recorded before and after the sympathetic trunk and white rami (WR) Th8-L3 were cut in a sequential manner. The step-by-step changes in the power of renal nerve discharge were estimated and used for mapping tonic renal outflow to the spinal cord. We found that powerful activity comprising 70-95% of the power of control recordings remained after eliminating the input from Th1-Th12, indicating that thoracic spinal cord including segments that contain the largest number of cells projecting to renal postganglionic neurons contributes relatively weakly to tonic renal nerve activity. It appeared that resting sympathetic nerve discharge was predominantly maintained by the caudalmost division of the renal preganglionic neuron population since the largest decrease in nerve power occurred after severing WR Th13, L1, and L2. These findings suggest that the 'active segmental map' of preganglionic neurons controlling a certain organ at rest does not necessarily match the distribution of the total population of neurons projecting to the same effector.