摘要:

SUMMARY1. The endothelium makes a significant contribution to the regulation of vascular tone through the release of potent vasodilator agents such as nitric oxide (NO) and prostacyclin (PGI2) as well as vasoconstrictor compounds such as endothelin. Recognition of this function of the endothelium has created a new focus for the investigation of vasoconstrictor activity under physiological and pathological conditions.2. It has been well established that removal of the endothelium enhances responses to a variety of contractile agents in conductance arteries and that such modulation is predominantly due to the release of NO. The use of selective inhibitors of NO synthesis has confirmed that the endothelium‐derived nitric oxide also modulates constriction in resistance vessels.3. In a number of cardiovascular disease states there is impairment of endothelial function. Thus one of the consequences of atherosclerosis, hypertension and ischaemia is a reduction in endothelium‐dependent vasodilatation, both at a basal level and in response to endogenous and exogenous stimuli. In addition, enhanced responses to vasoconstrictors have been reported in those disease states. Such observations have led to the attractive hypothesis that enhanced constriction in vascular disease results from attenuate NO‐induced dilatation. However, whilst there is some evidence that pathological impairment of endothelial function is accompanied by increased constrictor activity, particularly where serotonergic mechanisms are involved, it is inappropriate to make the general assumption that where disease impairs NO activity there will also be increased sensitivity to all constrictor st

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02071.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. Arterial blood pressure is maintained, and reflexly controlled, by the activity of neurons in the medulla and spinal cord.2. Rhythmic, automatic, respiratory activity is generated by neurons in the ventral medulla and transmitted to pre‐motoneurons and motoneurons in the medulla and spinal cord.3. Sympathetic nerve activity often has a respiratory rhythmicity.4. One site at which the interaction between respiratory and sympathetic neurons occurs is the ventrolateral medulla.5. Different types of sympathetic neurons, such as muscle vasoconstrictor, sudomotor and pilo‐erector, have different patterns of respiratory rhythmicity.6. Inputs from medullary respiratory neurons to medullary sympathetic premotor neurons may be the mechanism that co‐ordinates the activity of these two vital sy

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02072.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. We examined the proliferative rates of cultured astrocytes isolated from stroke‐prone spontaneously hypertensive rats (SHRSP) and stroke‐resistant spontaneously hypertensive rats (SHRSR). Wistar‐Kyoto rats (WKY) were used as a control for SHRSP and SHRSR.2. In the presence of 10% fetal bovine serum (FBS), the doubling time for astrocytes from SHRSP and SHRSR was significantly shorter than WKY.3. When quiescent astrocytes derived from SHRSP or SHRSR were released from serum‐deprivation, the DNA synthesis was stimulated 13.3‐fold and 12.5‐fold, respectively, whereas only a 7.76‐fold increase was observed in WKY astrocytes.4. Further we studied the effects of two growth factors, epidermal growth factor (EGF) and fibroblast growth factor (FGF) on astrocyte proliferation. EGF induced greater DNA synthesis in SHRSP and SHRSR astrocytes compared with WKY astrocytes, although FGF had little or no effect.5. Total cholesterol levels in SHRSP astrocytes and SHRSR astrocytes were significantly lower than that of WKY astrocytes, which was consistent with our previous observations in cultured vascular smooth muscle cells.6. There was no differece in morphology among the cultured astrocytes from the three strains.7. The abnormality of growth rate and cell membranes composition of astrocytes might be closely related to the genetic phenotypes (acute death of neurons and oedema of astrocytes) of S

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02073.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The present study was performed to investigate the effects of captopril (an angiotensin converting enzyme inhibitor, ACE‐I) on noradrenergic transmission in the rat central nervous system.2. Slices of rat hypothalamus and medulla oblongata were prepared and prelabelled with [3H]‐norepinephrine. Slices were continuously superfused with Krebs‐Ringer solution, and electrical stimulation (1 Hz) was performed.3. Captopril significantly inhibited the stimulation‐evoked [3H]‐norepinephrine release from rat hypothalamic slices in a dose‐dependent manner (S2/S1 ratio: control 0.904 ± 0.025,n= 6, captopril l × 10‐5mol/L 0.617 ± 0.043,n= 6,P<0.05, captopril 5 ×10‐5mol/L 0.547±0.037,n= 6,P<0.05). However, the basal release of [3H]‐norepinephrine was not affected by captopril.4. Captopril also reduced the stimulation‐evoked [3H]‐nor‐epinephrine release in the medulla oblongata (S2/S1 ratio: control 0.878 ± 0.018,n= 6, captopril 3.3 × 10‐5mol/L 0.624 ± 0.046,n= 6,P<0.05).5. These results show that captopril might inhibit the stimulation‐evoked norepinephrine release in rat hypothalamus and medulla oblongata. Although the precise mechanisms underlying the neurosuppressive effect of captopril are still uncertain, the finding suggests that the inhibition of noradrenergic transmission might be related

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02074.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The haemodynamic effects of rat adrenomedullin (AM), a novel hypotensive peptide, were examined in anaesthetized 16–18 week old spontaneously hypertensive rats (SHR) and Wistar‐Kyoto rats (WKY).2. An intravenous injection of rat AM dose‐dependently reduced the mean blood pressure (MBP) with a concomitant fall in total peripheral resistance index (TPRI) and an increase in cardiac index (CI) in both strains of rats. Per cent changes in MBP, TPRI and CI were not different between SHR and WKY.3. The plasma half‐life of rat AM in SHR was similar to that in WKY when it was administered at the dose of 1.0 nmol/kg.4. These findings indicate that AM has a potent vasorelaxant activity in both SHR and WKY. The haemodynamic responsiveness to exogenous AM and its pharmaeokinetics in SHR were comparable with those

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02075.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The rat and the guinea‐pig are commonly used animals when the effects of drugs on ciliary activity in respiratory airways are studied. There are few data concerning the possible differences in ciliary function between these two animals.2. Using a photodetector method we measured the ciliary beating frequency (CBF) from the upper part of the trachea, the lower part of the trachea and the distal part of the main bronchi (subsegmental bronchi) of rat and guinea‐pig respiratory tract. In addition, the structure of the cilia was studied using scanning electron microscopy (SEM).3. CBF in the rat respiratory tract was significantly lower than in the guinea‐pigs. In the upper trachea, the CBF for rat was 12.7 beats/s and 15.3 beats/s for guinea‐pig. The respective values were 9.2/16.0 beats/s in the lower part of the trachea and 6.9/13.8 beats/s in subsegmental bronchi. In both rats and guinea‐pigs CBF was lower in the subsegmental bronchi than in the trachea (rat: 25.0–45.7%, guinea‐pig: 9.8–13.8%).4. In addition to higher CBF, the quality of the photo‐electrical signal was better from guinea‐pig tissues, probably as a result of the larger amounts of ciliated cells and longer cilia of guinea‐pig respiratory epithelia compared to those in rat mucosa.5. SEM showed that the rat cilia were on average shorter (3.6vs4.3 μm) and thinner (0.19vs0.22 μm) than those of the guinea‐pig. Rat mucosa was markedly less ciliated than the respiratory mucosa of the guinea‐pig.6. Choice of animal species may affect the reliability and sensitivity of results when drug effects on ciliary function are studied. Guinea‐pig may be the most suitable choice as a laboratory animal, although guinea‐pig mucosa requires more careful handling than rat tissue in orde

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02076.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The present study investigated in conscious sheep the response of the sympathetic nervous system to a systemic infusion of 20 nmol/h endothelin‐1 (ET‐l), using a tritiated‐noradrenaline (NA) tracer dilution technique.2. Mean arterial pressure increased from 79 ±3 mmHg to a maximal level of 102± 12 mmHg by 30 min of ET‐1 infusion.3. Total and renal NA kinetics were measured during this time. Total NA spillover was not affected by infusion of ET‐1. In contrast, renal NA spillover decreased from a control level of 81 ± 5 to 30 ± 14ng/min (P<0.01) after 20 min and to 27 ± 7ng/min (P<0.01) after 30 min of ET‐1 infusion.4. The present findings are consistent with the proposal that a direct vasoconstrictor action of ET‐1 results in a paroreflex mediated reduction in renal sympathetic vasoco

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02077.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso‐pressin (AVP) release.2. Ethanol at a plasma concentration of 1.69 ±0.28 mmol/L produced an immediate increase in urine flow (174 ± 11 μL/min pre‐ethanol and 189 ± 13 and then 206 ± 12 μL/min during the ethanol infusion;P<0.001) as well as an increase in fractional sodium excretion (0.17 ± 0.04 to 0.28 ± 0.05 and 0.27 ± 0.05%;P<0.001). There was also a brief phosphaturia. These increases in electrolyte excretion had returned to control values by 20 min despite a further increase in the plasma ethanol concentration.3. The urinary excretion of potassium, calcium and magnesium was not altered nor was glomerular filtration rate or renal plasma flow.4. Ethanol at a mean concentration of 1.60 mmol/L did not alter the action of a maximal concentration of AVP (75 ng/kg) on water or electrolyte transport. However, the antidiuretic effect of a submaximal concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of 1.63 and 0.98 mmol/L.5. These studies suggest that the ethanol induced diuresis commonly ascribed to inhibition of AVP secretion may also be due to other intrarenal effects of ethanol, possibly acting within the proximal tubule. These results also confirm recentin vitrofindings that while ethanol does not inhibit the action of a maximal concentration of AVP, it does modulate the effects of lower AVP co

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02078.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The role of ATP sensitive potassium channels in the analgesic activity of prolactin (PRL) was studied in mice using glibenclamide and minoxidil, a blocker and an opener of these channel, respectively.2. Re‐treatment with glibenclamide attenuated the analgesic activity of PRL while treatment with minoxidil potentiated the activity.3. It is concluded that PRL, similar to morphine, utilizes ATP sensitive potassium channels in eliciting the analgesic respons

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02079.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The foreshortened 2 h method of measuring liquid gastric emptying (i.e. the proportional cumulative area under the curve of paracetamol) was utilized in diabetic patients in order to detect both gastroparesis and the influence of metoclo‐pramide, a known prokinetic drug, on this condition.2. Metoclopramide, 10 mg intravenously, caused a significant increase in the median PCAUCfrom 20 min onwards.3. In this study delayed gastric emptying was defined as a %PCAUCwithout pretreatment lower than the 5% percentile at 40, 60 and 90 min for normal volunteers. According to this criterion seven of the 10 patients with clinical symptoms of gastroparesis and/or peripheral neuropathy had delayed gastric emptying.4. The PCAUCmethod would therefore seem to be a reliable model for investigating gastric emptying in diabetics and the effects of various prokinetic drugs on this conditio

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb02080.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY