摘要:

We have investigated the role ofα‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptors on synaptic transmissionin vivobetween Ia primary afferents and cat spinal motoneurones using a selective non‐N‐methyl‐d‐aspartate (non‐NMDA) receptor antagonist, GYKI 52466.Both microionophoretic and intravenous application of GYKI 52466 depressed the Ia excitatory post‐synaptic potential (Ia EPSP) in a dose‐dependent manner, without any apparent effect on membrane conductance or resting potential of the motoneurone.GYKI 52466 reduced selectivelyα‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)‐ but notN‐methyl‐d‐aspartate (NMDA)‐induced depolarizations.Our results suggest that a large part of the Ia EPSP is mediated by AMPA receptors. The participation of other excitatory

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09537.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The interaction between dopaminergic and cholinergic systems in the mammalian central nervous system, which is thought to have important implications in the pathophysiology of major extrapyramidal disorders, has never been adequately demonstratedin vivo. Renshaw cell burst responses to single electrical shocks to lumbar ventral roots in spinalized and decerebrated rats were studied. In this monosynaptic cholinergic pathway, apomorphine, a dopaminergic receptor agonist, inhibited whereas the D2‐antagonist sulpiride facilitated the burst responses. The mutual antagonism of the two drugs and the depression coupled with the faster decay of post‐tetanic potentiation of Renshaw cells by apomorphine demonstrate the involvement of presynaptic D2‐receptors through which dopamine can modulate acetylcholine‐mediated central synaptic transmissionin vivo. The study also provides further evidence for the involvement of the spinal cord in extrapyramidal di

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09538.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Thalamic relay neurons were recorded from the dorsolateral and lateroposterior nuclei of the rat thalamus in a superfused explant preparation. The mean membrane potential of these cells was –67 ± 7 mV, input resistance 114 ± 31 MΩ and spike amplitude 75 ± 6 mV. Low‐threshold slow membrane potential oscillations (1–4 Hz) were present in about 46% of the neurons. They occurred either spontaneously or following a membrane potential perturbation. In a subpopulation of cells, we also observed a high‐threshold membrane oscillation when cells were depolarized above –45 mV. This oscillation consisted of bursts of low‐amplitude spikes interrupted by rhythmic afterhyperpolarizations. Stimulation of the corticothalamic pathway elicited prolonged inhibitory postsynaptic potentials in associational thalamic neurons. In the presence of picrotoxin, corticothalamic input evoked prominent excitatory postsynaptic responses that showed marked short‐term synaptic plasticity. Our results suggest that associational thalamic neurons maintainedin vitrohave a strong tendency to exhibit membrane oscillations. In addition, they receive a direct excitatory cortical input that remained functional in ex

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09539.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Levels of [Ca2+]iin rat cortex synaptosomes were measured using the Ca2+indicator Fura‐2. Ca2+influx was induced by veratridine in a concentration‐dependent manner (1–10μm). The resulting increase in [Ca2+]iwas inhibited by tetrodotoxin (TTX). K+(18 mm) increased the [Ca2+]iwhich was not influenced by TTX. K+‐channel blockers such as 4‐aminopyridine,α‐andδ‐dendrotoxinper sewere ineffective. The veratridineinduced Ca2+influx in synaptosomes was reduced by L‐type Ca2+‐channel blockers, such as felodipine, nifedipine and PN‐200‐110, verapamil and diltiazem.ω‐Conotoxin, an N‐type Ca2+‐channel blocker, did not inhibit the veratridine‐stimulated [Ca2+]iincrease. Bay K 8644, an L‐channel agonist, stimulated an increase of [Ca2+]iin synaptosomes which was not sensitive to TTX.R‐N6‐Phenyl‐isopropyl‐adenosine (R‐PIA) and clonidine, agonists at adenosine A1‐receptors and α2‐adrenoceptors, respectively, did not influence the veratridinestimulated [Ca2+]iincrease. R‐PIA did not interact with Bay K 8644‐stimulated [Ca2+]iincrease in synaptosomes.The results for all the substances used show major differences between the effects on Ca2+influx in synaptosomes and on the electrically evoked neurotransmitter release in slice preparations. Thus, the synaptosome preparation is not a generally applicable experimental model for the

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09540.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Regional electrical impedance was used over eight sections of the human body (two thoracic; one abdominal; two thigh; two around the knee; and one lower leg) to determine the volume indifference point during passive head‐up tilt in eight subjects. Head‐up tilt was performed in 10± increments from 0± to 60± over 6 min. Electrical impedance increased over the thorax in proportion to the head‐up tilt angle, while abdominal impedance did not change significantly, and over the thigh and the lower leg it decreased with increasing head‐up tilt angle. No change in electrical impedance was noted just above the knee, and electrical impedance just below the knee decreased only marginally. Results demonstrate minimal fluid accumulation around the knee during head‐up tilt. Furthermore, in humans the electrical impedance and therefore probably the volume indifference point is positioned between the umbilicus and c

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09541.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

To investigate the effect of endothelin on renin release, experiments were performed in barbiturate‐anaesthetized dogs with denervated kidneys. Intrarenal infusion of endothelin (1 ng min‐1kg‐1body wt) reduced renal blood flow (RBF) from 145 ± 10 ml min‐1to 98 ± 9 ml min‐1without altering renin release (1 ± 1μg angiotensin I (AI) min‐1). Renin release was then increased either by renal arterial constriction or ureteral occlusion. When renal arterial pressure was reduced to 50 mmHg, renin release averaged 79 ± 20μg AI min‐1in six dogs and fell significantly to 24 ± 6μg AI min‐1during endothelin infusion. During ureteral occlusion the inhibitory effect of endothelin on renin release either during inhibition ofβ‐adrenergic activity with propranolol or after inhibiting prostaglandin synthesis by indomethacin during intrarenal infusion of isoproterenol was examined. After propranolol administration ureteral occlusion increased renin release from 5 ± 2μg AI min‐1to 38 ± 12μg AI min‐1in six dogs. Subsequent intrarenal endothelin infusion (1 ng min‐1kg‐1body wt) during maintained ureteral occlusion reduced renin release to 10 ± 3μg AI min‐1. In six other dogs prostaglandin synthesis was inhibited by indomethacin. Subsequent infusion of isoproterenol (0.2μg min‐1kg‐1body wt) to stimulateβ‐adrenoceptor activity increased renin release from 13 ± 4μg AI min‐1to 68 ± 8μg AI min‐1during ureteral occlusion. Intrarenal endothelin infusion (1 ng min‐1kg‐1body wt) reduced renin release to 22 ± 3μg AI min‐1during continuous isoproterenol infusion and ureteral occlusion. Hence endothelin inhibits renin release induced by renal arterial constriction or ureteral occlusion. Similar inhibitory effects whether renin release was raised by increasing prostaglandin synthesis or by stimulatingβ‐adrenergic activi

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09542.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Nitric oxide plays an important role in the regulation of basal renal blood flow. This study was performed to examine whether selective inhibiti± of renal nitric oxide synthesis affects renin releasein vivo. Accordingly, in six barbiturate‐anaesthetized dogs renin release was examined before and after intrarenal infusion of the selective inhibitor of nitric oxide synthesis, NG‐nitro‐l‐arginine (NOARG). NOARG was infused into the renal artery to yield a renal arterial blood concentration of 0.4μmol ml‐1. NOARG did not change systemic arterial blood pressure and glomerular filtration rate, but reduced basal renal blood flow by 26 ± 2%. Urine flow, sodium and potassium excretion were reduced after inhibition of renal nitric oxide synthesis. Basal renin release (3 ± 2μg AI min‐1) was not altered by NOARG infusion (1 ± 1μg AI min‐1). To stimulate renin release the renal artery was constricted to a renal perfusion pressure of 50 mmHg. At this perfusion pressure infusion of NOARG reduced renin release significantly from 48 ± 11μg AI min‐1to 14 ± 4μg AI min‐1. In conclusion, inhibition of renal nitric oxide synthesis reduces basal renal blood flow and reduces renin release stimulated by renal arterial constriction. These findings indicate that renal nitric oxide modulates both renal blood f

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09543.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Effects of the GABAergic drug diazepam (0.15 mg kg‐1, i.v.) on cardiovascular and endocrine responses to 50± head‐up tilt were evaluated in seven men. During the initial phase of tilt (normotensive phase), increases in heart rate (HR) and total peripheral resistance (TPR) and decreases in cardiac output were unaffected by diazepam. Also the associated increase in plasma noradrenaline did not change, while response in plasma ACTH was diminished and in plasma cortisol abolished by diazepam (F(1, 10) = 6.45; P<0.03). After 42 ± 4 min of sustained tilt with saline (control) and 47 ± 6 min (n.s.) after diazepam, presyncopal symptoms appeared (hypotensive phase) associated with decreases in HR, MAP, and TPR (P<0.01). This episode induced a 2–3‐fold increase in plasma ACTH,β‐endorphin, prolactin, cortisol (<0.01), and a moderate increase in plasma adrenaline (P<0.05). Diazepam did not significantly change cardiovascular and endocrine responses to the hypotensive phase of tilt. Results indicate that diazepam attenuates the cortisol part of pituitary‐adrenal responses to moderate, but not to severe, central hypovolaemia in humans with no effect on cardiovas

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09544.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Small arteries of the mesenteric arcade from Wistar rats display rhythmic oscillations superimposed on the tonic contractile response when exposed to submaximal doses of noradrenaline. We have previously shown that mechanical removal of the endothelium abolishes these oscillations. In the present study different methods to eliminate or modify the influence of the endothelium were used in order to further characterize the mechanisms behind rhythmic contractions in these vessels.Endothelium was removed either mechanically or chemically by perfusing the vessels with 0.3% CHAPS. The absence of functional endothelium enhanced noradrenaline sensitivity and simultaneously abolished oscillations in tension and membrane potential, but did not affect resting membrane potential. The rhythmic activity was also reduced or abolished by exposure to haemoglobin, methylene blue, LY83583 orl‐NNA. Indomethacin and propranolol were without effect. Sodium nitroprusside or the permeant analogue of cyclic GMP, 8‐bromo cyclic GMP, restored rhythmic activity in precontracted endothelium‐denuded vessels. The data suggest that release of nitric oxide from the endothelium, and subsequent generation of cyclic GMP in the smooth muscle, activates oscillations in membrane potential and tension; the oscillator itself appears to be located within the smooth muscle

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09545.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Intravenous infusion of endothelin‐1 (ET‐1) in the cat, 60 pmol × kg body wt‐1x min‐1for 5 min, induced an increase in mean arterial blood pressure (MAP) of 41.3 ± 4.8 mmHg (n= 6;P<0.001). Blood flow, as determined with radioactive microspheres, was reduced in many tissues. Reductions by 70–80% were observed in the choroid plexus, pineal and pituitary glands. Total cerebral blood flow was reduced by 18–23%. Pre‐treatment with indomethacin or a combination of indomethacin andl‐NAME caused vasoconstriction in many tissues and modified the responses to ET‐1 in a variable way, suggesting that normally, ET‐1 tends to release arachidonic acid metabolites and nitric oxide with great variations between different tissues.Intracerebroventricular infusion (i.c.v.) of ET‐1, 10 pmol × kg body wt‐1x min‐1, caused an increase in MAP of 79 ± 11 mmHg (n= 6;P<0.001). Regional blood flow in the medulla oblongata, medulla spinalis, choroid plexus, pineal and pituitary glands was reduced by 60–80%. Heart rate, cardiac output and coronary blood flow were significantly increased after 30 min i.c.v. infusion, indicating an activation of the heart, most probably as part of a central ischaemic response.Our results indicate that in many tissues the vasoconstrictive effect of ET‐1 is influenced by indomethacin‐ andl‐NAME‐sensitive vasodilator mechanisms that are activated by the peptide. In the CNS, there may be marked effects on re

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1993.tb09546.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY