bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence that prejunctional adenosine receptors regulating acetylcholine release from rat hippocampal slices are linked to an N‐ethylmaleimide‐sensitive G‐protein, but not to adenylate cyclase or dihydropyridine‐sensitive Ca2+‐channeIs
Authors: DUNÉR‐ENGSTRÖM M. , FREDHOLM B. B.
Published: December 2008

Electrically evoked [3H]acetylcholine ([3H]ACh) release from slices of the rat hippocampus was reduced in a dose‐dependent manner by the adenosine A,‐receptor agonist R‐phenylisopropyladenosine (R‐PIA) in the concentration range 0.1–10 μM. The maximal effect was observed with I μM R‐PIA. Treatment withN‐ethylmaleimide (NEM, 100 μ M, 10 min), which inactivates nucleotide‐binding proteins (G‐proteins), caused a slight increase in the basal overflow (0.17 ± 0.01%v. 0.10 ± 0.003% in the control slices), but did not affect stimulated release (0.73 ± 0.05%vs. 0.74 ± 0.03% in the control slices).N‐ethylmaleimide pretreatment significantly reduced the prejunctional inhibitory effect of R‐PIA on [3H]ACh release in a non‐competitive manner. The S2/S1ratio was 0.92 ± 0.03 in controls and was reduced to 0.32 ± 0.02 by I μ Mm R‐PIA in the control slices and to 0.57 ± 0.03 after NEM pretreatment. Stimulation of cyclic AMP‐accumulation by forskolin (I μ M) and rolipram (30 μ M) before the second stimulation (S2) enhanced the S2/S1ratio by about 30% to 1.26 ± 0.12, but did not reduce the inhibitory effect of R‐PIA (I μ MM). The Ca2+‐channel agonist Bay K 8644 (I μ MM), a concentration that increases K+‐evoked noradrenaline release, did not affect the basal or electrically evoked [3H]ACh overflow, or the prejunctional effects of R‐PIA (0.1 and I μ MM) on [3H]ACh release. Our results suggest that the presynaptic inhibitory effects of A1‐receptor agonists on [3H]ACh release are exerted via a nucleotide‐binding protein that can be inhibited by NEM. However, the inhibitory effect is apparently not caused by a change in adenylate cyclase activity or by affecting dihydropyridine‐sensitive Ca2+‐channels.
Effects of exercise and CO2 inhalation on the breathing pattern in man
Authors: ELLINGSEN I. , SYDNES G. , HAUGE A. , NICOLAYSEN G.
Published: December 2008

Conflicting opinions exist concerning the breathing pattern in man during resting and stimulated ventilation. Some but not all investigators have reported the existence of an abrupt change, a ‘breakpoint’, in the relation between mean tidal volume and mean inspiratory time. Different opinions exist as to whether the slope and the intercept for the relation between mean minute ventilation and mean tidal volume are identical regardless of the mode of stimulating the ventilation. We have studied 10 subjects, at rest and during graded stimulation of ventilation by CO2 inhalation and exercise. No breakpoint was observed in the relations between (I) mean tidal volume and mean inspiratory time and (2) mean tidal volume and mean expiratory time, even if a wide range of tidal volumes was achieved in our subjects. Carbon dioxide inhalation (normoxic or hyperoxic) and exercise gave different regression lines for the relation between mean minute ventilation and mean tidal volume in 8 out of 10 subjects with a larger slope during exercise. At exercise inspiratory time decreased with any increase in tidal volume, while during CO2 breathing no consistent change in inspiratory time was seen. Mean inspiratory flow was linearly related to exercise load and apparently also to arterial carbon dioxide pressure. We conclude that CO2 breathing gives a breathing pattern which is different from that obtained with exercise in the majority of normal subjects. Furthermore, we could not confirm the existence of breakpoints in relations describing the breathing pattern of normal man.
Effects of adrenaline on excitation‐induced stimulation of the sodium‐potassium pump in rat skeletal muscle
Authors: EVERTS M. E. , RETTERSTØL K. , CLAUSEN T.
Published: December 2008

Experiments were performed on isolated rat soleus and extensor digitorum longus (EDL) muscles of 4–week‐old rats. In the soleus, direct electrical stimulation for 10 min induced a frequency‐dependent increase in the ouabain‐suppressible 86Rb+ uptake, which was maximal (+110%) at a frequency of 2 Hz. In the EDL this frequency only induced a 31% increase. A supramaximal concentration of adrenaline (10μmol l‐1) stimulated ouabain‐suppressible 86Rb+ uptake by 80% and 27% in soleus and EDL, respectively. The combined effect of stimulation at 2 Hz and adrenaline was not significantly larger than each of the interventions alone in either of the muscles. The fractional loss of 22Na+ from soleus muscle was increased by around 50% by the exposure to adrenaline, electrical stimulation at 2 Hz or a combination of both. The effect of electrical stimulation on 22Na+ efflux was not prevented by addition of propranolol (I or 10μmol 1–1).

The results indicate that the stimulation of active Na+‐K+ transport induced by adrenaline or electrical stimulation is much more pronounced in soleus (slow‐twitch) muscle than in EDL (fast‐twitch) muscle. Since it has been suggested that an accumulation of K+ ions in the extracellular space may play a role in the development of fatigue (Bigland‐Ritchie 1984), our findings might be related to the fact that slow‐twitch muscles have a much higher resistance to fatigue than fast‐twitch muscles (Burke et al. 1971).
Back‐leak of pelvic urine to the bloodstream
Authors: STENBERG A. , BOHMAN S.‐O. , MORSING P. , MÜLLER‐SUUR C. , OLSEN L. , PERSSON A. E. G.
Published: December 2008

The aim of the present investigation was to measure the back‐leak of pelvic urine to the blood circulation. In normopenic hydronephrotic, dehydrated hydronephrotic and dehydrated control kidneys the back‐leak was estimated from a servocontrolled machine which regulated infused saline to keep a preset pelvic pressure constant. The disappearance of fluid from the renal pelvis could be measured at different pressure levels, and a pressure‐dependent outflow of fluid was found. From these measurements a back‐leak conductance could be calculated which proved to be independent of pressure. In the lower pressure range (15–20 mmHg) there was a significantly lower conductance in the dehydrated controls compared with the dyhydrated hydronephrotic kidneys, while in the higher pressure range (25–30 mmHg) no difference was found. From electron microscopical studies the pyelorenal back‐leak of fluid in both hydronephrotic and control animals seemed to be most pronounced in the fornix region, as documented by a heavy presence of horseradish peroxidase in the intercellular spaces there. Other experiments with radioactively labelled inulin, which was injected into the pelvic cavity, indicated that most of the back‐leak occurred via the renal blood vessels and not through the lymphatic system. The importance of this back‐leak was evident from the measurements of the total kidney glomerular filtration rate (GFR) at a slightly increased pelvic pressure, where some of the urine with radioactive tracer flows back to circulation. The back‐leak of pelvic urine could also affect the concentration mechanism by removing diluted urine which had flowed over the renal papilla, and through water and urea diffusion increased papillary interstitial osmolarity.
Myelin basic protein present in the acid extracts of rat hypothalami releases insulin and glucagon from isolated rat pancreatic islets
Authors: LEPPÄLUOTO J. , ZEYTIN F. , UENO N. , YING S.‐Y. , LING N. , GUILLEMIN R.
Published: December 2008

The insulinotropic and glucagon‐releasing activity of acid extracts of rat hypothalami were tested in two bioassay systems using short‐time incubation of isolated rat pancreatic islets and a rat insulinoma (RIN) cell line. Release of insulin and glucagon into the incubation medium was measured by radioimmunoassay. The major insulin‐releasing and glucagon‐releasing activity eluted in a broad zone in Sephacryl S‐zoo gel filtration in 30% acetic acid corresponding to the molecular weights between approximately 10 and 40 kD. The highest activity was eluted in a zone corresponding to 14 kD and was purified to homogeneity by means of two steps of reversed—phase HPLC. Amino acid analysis and SDS polyacrylamide gel electrophoresis indicated that the biologically active material was the rat small (myelin) basic protein characterized previously by Dunkley & Carnegie (1974). The purified rat hypothalamic material showed insulinotropic and glucagon‐releasing activity indistinguishable from that of purified porcine myelin basic protein, and lost its insulinotropic activity when incubated with anti‐myelin basic protein immunosorbent.

We conclude that the major insulin‐releasing and glucagon‐releasing activity in acid extracts of the high‐molecular‐weight fractions of rat hypothalami is myelin basic protein.
Sympathetic modulation of the jaw‐opening reflex in anaesthetized rabbits
Authors: AARS H. , BRODIN P. , BJØRNLAND T.
Published: December 2008

The influence of sympathetic nerve stimulation (SNS) on the digastric muscle response to tapping on a front tooth was investigated in 14 anaesthetized rabbits. The reflex response to transverse taps was measured as changes in EMG activity of the ipsilateral digastric muscle. With taps of 1.1–2.2 times the threshold, the amplitude of the digastric EMG response was reduced by stimulation of the cervical sympathetic trunks (0.5–10.0 Hz) in 35 out of 40 test series. Maximum effect was observed at 6 Hz, which produced an average inhibition of 82 %. The sympathetic effect appeared a few seconds after the start of stimulation, and in the range 0.5–6 Hz increased with the stimulation frequency. It was blocked by phenoxybenzamine. The reflex was triggered by receptors in or around the tooth, since it disappeared after sectioning of the inferior alveolar nerve (IAN) or local anaesthesia of the tooth. Afferent electrical stimulation of the IAN evoked a digastric excitation that was insensitive to SNS. We conclude that the sympathetic inhibition of the reflex was mediated by a local action in the receptor area, probably related to the evoked vasoconstriction.
Distribution of recurrent inhibition within a motor nucleus. II. Amount of recurrent inhibition in motoneurones to fast and slow units
Authors: HULTBORN H. , KATZ R. , MACKEL R.
Published: December 2008

The maximal recurrent inhibition was studied by intracellular recording from 43 triceps surae motoneurones (tentatively type‐identified by the biophysical properties of the neurones) and from 67 medial gastrocnemius motoneurones (type‐identified by the muscle unit properties; fast fatiguing, FF; fatigue resistant, FR and slow, S). Maximal homonymous recurrent IPSP (RIPSP) and input resistance (Rn) were measured at ‘resting’ membrane potential and close to firing threshold. The ‘synaptic current’ at the peak of the RIPSP was estimated (RIPSP/Rn).

At ‘resting’ membrane potential the RIPSPs increased in the order FF < FR < S (0.9, 1.4, and 2.5 mV, respectively). This order was preserved when the ‘current’ (RIPSP/Rn) rather than voltage was considered, although the overall range was much reduced. When investigated close to firing threshold there were no significant differences in synaptic ‘current’. This apparent paradox may be explained by systematic differences in firing threshold between motor unit types; it increased in the order S < FR < FF (4.6, 8.9 and 13.5 mV, respectively).
Transcapillary albumin extravasation in rat skin and skeletal muscle: effect of increased venous pressure
Authors: REED R. K.
Published: December 2008

Plasma‐to‐tissue transport of radioactively labelled albumin has been used to study the effect of increased venous pressure on transcapillary albumin transport. Venous pressure was increased by inflating a balloon catheter in the inferior caval vein. Plasma‐to‐tissue transport of albumin was taken as the extravascular distribution space (EValb) for 125I‐labelled human serum albumin (I‐HSA) after I h. Venous pressure was increased from 2 to 20 mmHg in the experimental group. Interstitial fluid volume (IFV) was measured as the extravascular distribution space for 51Cr‐EDTA. In control EValb was 9.24 × 10‐‐3 ml g‐1 d. wt (SD = 1.28, n= 8) and 3.67 × 10‐‐3 ml g‐1 d.wt (SD = 0.94, n= 8) in skin and skeletal muscle, respectively. Increasing venous pressure raised EValb and IFV in skin and skeletal muscle, but the increase in EValb was about 3 and 5 % of the rise in IFV, resulting in capillary reflection coefficients for albumin of 0.94 in skin and 0.98 in skeletal muscle. The low transcapillary albumin transport relative to water transport is‐compatible with a two‐pore model of transcapillary exchange where large pores (250 Å) accounts for less than 5.5 and 2.5% of the total capillary filtrate of fluid in skin and skeletal muscle, respectively.
Atrial natriuretic factor, urinary catechol compounds and electrolyte excretion in rats during normal hydration and isotonic volume expansion. Influence of dopamine receptor blockade.
Authors: HANSELL P. , ANDE'N N.‐E. , GRABOWSKA‐ANDE'N M. , ULFENDAHL H. R.
Published: December 2008

To investigate the influence of acute isotonic volume expansion (VE) on the plasma concentration of atrial natriuretic factor (ANF), the excretion of catechol compounds and electrolytes and the whole kidney glomerular filtration rate (GFR), these variables were measured before and during 60 min ofVE(2% of body weight per hour). Atrial natriuretic factor was measured at the end of the experiment. In a control group (n= 7) without volume expansion, plasma ANF was 58 ± 4 pg ml‐1. The excretion of sodium, dopamine (DA),3,4–dihydroxyphenylacetic acid (DOPAC), noradrenaline (NA) andGFRdid not change during the control study. InVEanimals (n= 7) plasma ANF was 82 ± 7pg ml‐1, significantly higher than in the control group. Sodium excretion increased more than 17–fold. The excretion of the DA increased by 38% and that of DOPAC by 30%. Noradrenaline excretion remained unchanged whileGFRincreased by 20%. In haloperidol‐pretreated animals subjected toVE (n =7). plasma ANF was 81± 8 pg ml‐1duringVE, significantly higher than in the control animals. Although the sodium excretion increased more than ninefold in this group duringVE, this increase was only 55 % of that in theVEgroup not given haloperidol. The DA and DOPAC excretion was increased by haloperidol, indicating a feedback effect of receptor blockade. DOPAC excretion was not increased further byVE, hut the excretion of DA increased by 15% andGFRincreased by 19%. In conclusion, haloperidol reduced the natriuretic response toVEwithout impairing either the VE‐induced release of ANF or the increase inGFR. The results indicate an important involvement of ANF and DA in the natriuretic response toVE.
Orthograde and retrograde axonal transport in the regenerating frog sciatic nerve show different sensitivities to vanadate
Authors: EDSTRÖM A. , KANJE M. , RUSOVAN A.
Published: December 2008

The outgrowth region of the regenerating frog sciatic nerve shows an increased permeability for various drugs. The present experiments indicate that this is also true for vanadate, a substance of special interest in relation to axonal transport. Six days after a bilateral crush lesion, the sciatic nerves, including the spinal ganglia, were incubated in a compartmented chamber. Orthograde transport was assessed from the distribution and the accumulation of [3H]leucine‐labelled proteins in the nerve growth region. Retrograde transport was examined by allowing orthogradely transported labelled materials to reverse at the regenerating region and then to accumulate at a ligature during a second incubation period. Vanadate at 0.5 mM and higher concentrations was found to inhibit orthograde and retrograde transport in the outgrowth region (6 mm long at 6 d after crush), whereas 0.2 mm vanadate inhibited transport only in the retrograde direction. The observations lend further support to the idea that the mechanisms of transport in the two directions are different.
Sympathetic vascular control of the pig nasal mucosa (III): co‐release of noradrenaline and neuropeptide Y
Authors: LACROIX J. S. , STJÄRNE P. , ÄNGGÄRD A. , LUNDBERG J. M.
Published: December 2008

The overflows of noradrenaline (NA) and neuropeptide Y like immunoreactivity (NPYLI) and vascular responses upon sympathetic nerve stimulation were analysed in the nasal mucosa of pentobarbital anaesthetized pigs. In controls, a frequency‐dependent increase in NA overflow was observed whereas detectable release of NPY‐LI occurred only at 6.9 Hz. Parallel decreases in blood flow in the sphenopalatine artery and vein and in nasal mucosa volume (reflecting blood volume in the venous sinusoids) were observed. The laser Doppler flowmeter signal (reflecting superficial blood flow) increased upon low and decreased upon high frequency stimulation. Twenty‐four hours after reserpine pretreatment and preganglionic decentralization, the NA overflow was abolished while a frequency‐dependent release of NPY‐LI occurred. Forty, 60 and 80% of the vasoconstrictor responses then remained upon stimulation with a single impulse, 0.59 and 6.9 Hz, respectively. Both the vasoconstriction and NPY‐LI overflow, however, were subjected to fatigue upon repeated stimulation. In reserpinized animals release of NPY‐LI and vasoconstrictor responses were larger upon stimulation with irregular bursts at 0.59 Hz compared to effects seen at stimulation with continuous impulses. Pre‐treatment with the a‐adrenoceptor antagonist phenoxybenzamine or the monoamine reuptake inhibitor, desipramine, enhanced NA overflow by 2–3 and 1.5 times at 0.59 and 6.9 Hz, respectively. Phenoxybenzamine significantly reduced the nerve‐evoked vascular responses while the release of NPY‐LI at 6.9 Hz was increased. Desipramine increased the functional responses but reduced the NPY‐LI overflow. During tachyphylaxis to the vasoconstrictor effects of the stable adenosine 5′‐triphosphate (ATP) analogue α‐β‐methylene ATP (mATP) in controls, the vasoconstrictor responses as well as the NA and NPY‐LI overflow to nerve stimulation were unmodified. In reserpinized animals, however, the vascular responses and the overflow of NPY‐LI were reduced after mATP tachyphylaxis.

These data show that both NA and NPY are released upon sympathetic nerve stimulation in the nasal mucosa in vivo and this release seems to be regulated via prejunctional a‐adrenoceptors. The lack of effect of mATP tachyphylaxis under control conditions makes it less likely that ATP serves as a major mediator of the large nonadrenergic vasoconstrictor component.
The influence of antihypertensive treatment on the mesenteric arterial structure in spontaneously hypertensive rats. A morphometric study
Authors: NORDBORG C.
Published: December 2008

Spontaneously hypertensive rats (SHR) and stroke‐prone spontaneously hypertensive rats (SHRSP) were treated with a combination of a beta1‐blocker (metoprolol) and a calcium antagonist (felodipine) from 1 to 4 or from 4 to 6‐months of age. The main trunk and peripheral branches of the mesenteric arterial tree were fixed by immersion and embedded in plastic. The total length of the internal elastic membrane and the media area were measured in cross‐sectioned arteries. The ratio between media thickness (m) and lumina radius (ri) was then determined for a calculated, standardized condition, assuming a smooth and circular internal elastic membrane. The treatment caused a significant decrease in blood pressure and a reduction in m/ri ratios in the mesenteric arterial trunk as well as in mesenteric arterial branches when initiated in young as well as in adult SHR and SHRSP, i. e. the therapy efficiently prevents as well as reverses hypertensive arterial changes. The m/ri ratios in the superior mesenteric arterial trunks were significantly smaller in treated 4‐month‐old SHR and SHRSP than in WKY, although their blood pressures were not fully normalized. There was a marked increase in luminal radius in the young treated rats, possibly secondary to a therapy‐induced increase in splanchnic blood flow.
Phorbol ester desensitization of clonal insulin‐releasing cell response to carbachol involves depletion of an intracellular calcium pool
Authors: GYLFE E.
Published: December 2008

The mechanism by which 12‐o‐tetradecanoylphorbol‐13‐acetate (TPA) desensitizes carbachol mobilization of glucose‐incorporated calcium (Ca2+) was studied in clonal insulin‐releasing cells (RINm5F) using colour indicators and dual wavelength spectrophotometry. The net uptake of Ca2+stimulated by 20 mm glucose reached saturation after 19 ± 2 min when it corresponded to 1.21 ± 0.09 mmol calcium kg‐1protein. Carbachol then induced a release of 0.21 ± 0.03 mmol calcium kg‐1protein. Half of the remaining Ca2+was liberated by antimycin A and the rest with the Ca2+ionophore A‐23187. When 0.1 /μm TPA was added initially, the cells lost 0.29 ± 0.08 mmol calcium kg‐1protein within ro min. The subsequent addition of glucose resulted in a sluggish uptake of only 0.58 ± 0.09 mmol calcium kg‐1protein reaching equilibrium after 35 ± 3 min. Carbachol now failed to induce any Ca2+release. The actions of TPA were essentially unchanged by previous exposure to glucose, removal of Na+from the medium and even when some of the glucose‐incorporated Ca2+had been liberated with carbachol. The results indicate that TPA desensitization of carbachol‐induced mobilization of Ca2+in the RINm5F cells is due to the disappearance of Ca2+from the sensitive pool, an effect which may depend on stimulated extrusion of Ca2+from the cells by the (Ca2+‐Mg2+)‐ATPase.
Functional and biochemical analyses of isolated rat hearts in renal and reversed renal hypertension
Authors: FRIBERG P. , RUPP H. , NORDLANDER M.
Published: December 2008

The present study evaluates cardiac function, plasma renin activity (PRA) and left ventricular (I.V) myosin isoenzymes in untreated two‐kidney, one‐clip Goldblatt hypertensive rats (2K1C) and in 2K1C treated with felodipine and metoprolol. Normotensive rats (NCR) and another group of 2K1C, in which the renal artery constriction was removed (UC‐2K1C), were also investigated. Cardiac performance was assessed by means of a working heart perfusion device, allowing also for measurements of myocardial oxygen consumption.

Following antihypertensive therapy and unclipping, blood pressure became close to normotensive levels. PRA remained equally elevated in treated and untreated 2K1C, but became practically normalized after unclipping. Relative LV weight in 2K1C increased 74% above that in NCR but in treated 2K1C increased by only 20%. In UC‐2K1C LV hypertrophy became reversed, LV weight/body being about the same as in treated 2K1C. In treated 2K1C, coronary resistance at maximal dilatation was significantly reduced, implying prevention of hypertensive, structural coronary vascular changes, and optimal LV function was improved markedly in the lower range of perfusion pressures compared with untreated 2K1C. When, however, the hearts were challenged at a high pumping resistance (perfusion pressure), I.V function was similar in untreated and treated 2K1C. Myocardial oxygen consumption for given levels of stroke work was significantly lower in treated than in untreated 2K1C. The myosin isoenzyme pattern in the LV of 2K1C was shifted, with significantly higher amounts of VM‐3 than in NCR. This shift was normalized by antihypertensive therapy or by unclipping.

In conclusion, antihypertensive therapy with felodipine and metoprolol prevents the development of coronary vascular and left ventricular hypertrophy in 2K1C. This may contribute to enhance cardiac performance at low aortic pressure. The lack of improvement in optimal cardiac performance (at high aortic pressure) implies that the hypertensive stateper se, rather than extent of pressure elevation, cardiac hypertrophy, or changes of LV isoenzymes, determines the reduced cardiac function in renal hypertensive rats (Friberg & Nordborg 1986).
Mechanoreceptive units in the human infra‐orbital nerve
Authors: NORDIN M. , HAGBARTH K.‐E.
Published: December 2008

Eighty‐four low‐threshold mechanoreceptive afferents innervating facial hairy skin or the red zone of the lip were recorded with micro‐electrodes from the human infra‐orbital nerve. Based on their responses to skin indentations, the units were classified as slowly or fast‐adapting, with small or large receptive fields. The responses to hair movement, skin stretching and contraction of facial muscles were also studied.

Both hairy skin and the red zone were innervated by slowly and by fast‐adapting units. The innervation density was found to be highest at the corner of the mouth and on the upper lip. Slowly adapting units with small fields in hairy skin were most common and included units responding to sustained hair displacement. These units are suggested to have two types of end‐organs, either pilo‐Ruffini endings or Merkel cell‐neurite complexes. The slowly adapting units with large fields were spontaneously active stretch receptors and may have corresponded to Ruffini corpuscles, although the possibility of other, intramuscular, receptors could not be ruled out. Only one afferent possibly innervated a Pacinian corpuscle.

Most mechanoreceptors were also activated by skin stretching or contraction of facial muscles. Many of the slowly adapting units with small fields responded to the onset and release of stretch, whereas their discharge in response to sustained stretching adapted more or less completely. Spontaneously active units had the most sustained stretch response. It is concluded that several types of cutaneous mechanoreceptors can operate as sensitive proprioceptors of importance for facial kinaesthesia and motor control.
Environmental factors contribute to the enhanced regeneration of frog sciatic sensory axons by a conditioning lesion
Authors: EDBLADH M. , EDSTRÖM A.
Published: December 2008

The outgrowth of regenerating frog sciatic sensory axons after a crush lesion was measured from the distribution of axonally transported radioactive proteins. Five days after a single test crush the regeneration distance was 3.6±0.3 mm. If the nerve was subjected to a conditioning lesion 15 mm distal to and 5, 10 or 17 days prior to the test crush, there was an increased outgrowth distance (5.1±0.2 mm) 5 days after the test crush when the conditioning interval was 10 days. Prolongation of the time interval between the two lesions to 17 days did not significantly change the enhanced outgrowth. In contrast, if the conditioning and test lesions were applied at the same site, the regeneration distance 5 days after the test crush was already significantly increased after a conditioning interval of 5 days (5.9±0.5 mm). It was further enhanced after an interval of to days (7.8±0.5 mm) and yet further after 17 days (9.2±0.5 mm). When the conditioning and test lesions were superimposed, the regeneration occurred through a region of the nerve that was pre‐degenerated due to the conditioning lesion. The positive correlation between the degree of degeneration and the outgrowth distance supports the theory that environmental factors contribute to the regenerating ability of peripheral nerves.
Differential release of calcitonin gene‐related peptide and neuropeptide Y from the isolated heart by capsaicin, ischaemia, nicotine, bradykinin and ouabain
Authors: FRANCO‐CERECEDA A. , SARIA A. , LUNDBERG J. M.
Published: December 2008

The influence of various drugs as well as total ischaemia on the outflow of calcitonin gene‐related peptide (CGRP), which is present in sensory nerves, and neuropeptide Y (NPY), which is co‐stored with noradrenaline (NA), from the isolated guinea‐pig heart, was studiedin vitro. Capsaicin exposure and total ischaemia for 5–30 min induced a Ca2+‐dependent increase in the outflow, suggesting release, of CGRP‐ but not NPY‐like immunoreactivity (LI) from the heart. When characterized by high performance liquid chromatography (HPLC), the CGRP‐LI present in heart extracts and the released CGRP‐LI by capsaicin eluted in a major peak corresponding to synthetic CGRP. Incubation with morphine, indomethacin or reserpine pretreatment did not influence the capsaicin‐evoked release of CGRP‐LI. Capsaicin pretreatment depleted the cardiac content of CGRP‐LI but not NPY‐LI. The increase in perfusate volume observed after 30 min ischaemia in controls was reduced after capsaicin pretreatment. Nicotine exposure induced release of CGRP‐ as well as NPY‐LI in a concentration‐ and Ca2+‐dependent manner. The increased outflow of NPY‐LI was not influenced by capsaicin pretreatment. Among other agents tested, bradykinin and ouabain caused increased outflow of CGRP but not of NPY‐LI. Noradrenaline, tyramine, histamine, vasopressin, α,β methylene ATP, ATP or adenosine induced changes in cardiac contractility or flow but did not evoke any detectable release of CGRP‐ or NPY‐LI. In conclusion, the release of multiple neuropeptides can be studied in combination with contractile recordings using the isolated perfused guinea‐pig whole heart preparation. Activation of cardiac sensory nerves by capsaicin, nicotine, bradykinin and ouabain, as well as ischaemia, induced release of CGRP while nicotine also evoked NPY release.
Sympathectomy provides evidence of dopamine storage in rat laryngeal nerve paraganglia
Authors: DAHLQVIST Å. , PEQUIGNOT J. M. , HELLSTRÖM S.
Published: December 2008

Catecholamine content in the recurrent and superior laryngeal nerves (RLN and SLN) of the rat was analysed by high‐performance liquid chromatography after surgical and chemical sympathectomy. Sympathectomy induced by repeated injections of guanethidine did not lead to any change in the dopamine (DA) level, whereas the noradrenaline (NA) content decreased by 68% and 64% respectively in the RLN and SLN. Surgical excision of the superior cervical ganglion (SCG) did not alter the level of DA in the SLN, but caused a 60% decrease of DA in the RLN. Removal of SCG did not affect the NA levels either in the RLN or in the SLN, unless it was combined with extirpation of the middle cervical ganglion, which induced a decrease in NA in both nerves. The results indicate that much of the DA in the laryngeal nerves is stored outside the sympathetic nerve fibres, probably in the small organs earlier characterized as endoneurial paraganglia.
Unitary activity in the bed nucleus of the stria terminalis after homo‐ and contralateral stria terminalis stimulation
Authors: YAJEYA J. , GUTIERREZ J.CRIADO , De MOLINA A.FERNANDEZ
Published: December 2008

Acute experiments were performed on anaesthetized rats using standard techniques of electrical stimulation and single‐unit recording in order to study the responses of the bed nucleus of the stria terminalis (BNST) neurons to homo‐ and contralateral stria terminalis (ST) inputs. Satisfactory records were obtained from 174 BNST neurons. The majority of these fired spontaneously at variable rates, with single random‐occurring spikes. The stria terminalis inputs are able to influence the discharges of many BNST neurons. Homolaterally the response patterns consisted of: (a) an excitatory–inhibitory sequence with variable latency in 61% of the cells; (b) a pure inhibitory period in 23% of the cells; (c) an inhibitory period followed by excitation in 2%; (d) no changes in 13% of the cells. The most frequent response to contralateral ST stimulation was excitation followed by inhibition (46%) and pure inhibition (28%).A high proportion of the cells (27%) did not show any change. These results correlate well with neuro‐anatomical studies of ST distribution on the BNST nucleus. Our finding of the high proportion of BNST cells affected in their discharge frequency by ST stimulation together with the variability of the observed responses is an indication of the close amygdala‐BNST relationship and also of the diverse functions in which both structures are involved.
Extravascular arteriovenous oxygen shunting in the cat stomach
Authors: IVARSSON L. , NILSSON N.J. , LUNDGREN O.
Published: December 2008

Venous appearance of oxygen and red cells labelled with methaemoglobin was compared in the gastric vascular bed. At ‘resting’ gastric blood flow the red cells appeared earlier than oxygen after simultaneous close i. a.injection, as would be expected from the intravascular laminar flow profile. However, when lowering arterial inflow pressure to the stomach by partially occluding the coeliac trunk, oxygen often appeared earlier than the red blood cells. When arterial pressure was lower than 50 mmHg this was always the case. This observation is taken to indicate that during these experimental conditions an extravascular shunting of oxygen occurs. It is suggested that this may occur in the submucosal vascular network and/or in the mucosa. The functional implications of such a mechanism are tentatively discussed.
Relationship between renal sympathetic activity and diuretic effects of atrial natriuretic peptide (ANP) in the rat
Authors: PETTERSSON A. , HEDNER J. , HEDNER T.
Published: December 2008

The effects of various adrenergic agonists and antagonists on the diuretic/natriuretic effects of rANP (103–125) were investigated in conscious and anaesthetized normotensive rats. Pharmacological sympathetic inhibition by reserpine completely inhibited the diuretic/natriuretic effects of ANP.However, surgical renal nerve denervation did not influence the renal response to ANP.Further studies using various pharmacological agents which interfere with adrenergic activity revealed that the diuretic mechanism of action differed between conscious and anaesthetized animals. In the anaesthetized group only, dopamine (D1) blockade reduced ANP‐induced diuresis. In the conscious as well as anaesthetized rats, however, pre‐synaptic dopamine (D2) stimulation and x2adrenergic receptor blockade effectively inhibited the renal response to ANP.The results of this study are compatible with the notion that ANP acts indirectly within the kidney via interaction with dopamine‐containing neuronal or non‐neuronal structures in the kidney.
Topographical localization of muscle glycogen: an ultrahistochemical study in the human vastus lateralis
Authors: FRIDÉN J. , SEGER J. , EKBLOM B.
Published: December 2008

The fine structural pattern of glycogen storage in resting and sprint‐exercised human vastus lateralis muscle fibres of different types was analysed using ultrahistochemical methods. Three male subjects (31–36 years) performed 60 consecutive, supramaximal bouts of bicycle exercise, each starting every 1 min and having a duration of 8 s (including approximately 3 s of acceleration). The load was estimated to correspond to 200% of VO2‐max. Five other subjects (22–27 years) constituted controls. Ultrathin sections stained with periodic acid‐thiosemicarbazide‐silver proteinate (PA‐TSC‐SP) clearly revealed a compartmental distribution of glycogen. Glycogen is stored at five topographically, and probably also functionally, different locations. They are the subsarcolemmal, intermyofibrillar, para‐Z‐disc, N2‐line, and H‐zone spaces. During the exercise, glycogen from the N2 line and para‐Z‐disc locations is preferentially utilized. Serial sections stained with uranyl acetate and lead citrate demonstrated that glycogen stores of the type 2 fibres were more depleted than those of type 1 fibres. The implications of the differential intracellular glycogen storage are discussed
Both the cholinergic and non‐cholinergic components of airway excitation are inhibited by morphine in the guinea‐pig
Authors: JOHANSSON I.G.M. , GRUNDSTRÖM N. , ANDERSSON R.G.G.
Published: December 2008

In order to investigate the effect of morphine on the excitatory and inhibitory non‐adrenergic, non‐cholinergic (NANC) neurotransmission and cholinergic neurotransmission in airways, ring preparations from guinea‐pig trachea and bronchi were studied. The preparations were stimulated by electrical field stimulation to elicit contractions and relaxations. Both cholinergic and NANC contractions were reduced by morphine in a dose‐dependent way, while the inhibitory NANC neurotransmission was unaffected. A morphine concentration of 10‐4m reduced the NANC contractions to 20.8± 1.5% of the control contractions and the cholinergic contractions to 49.7±4.2%. The effect of morphine on cholinergic neurotransmission was completely inhibited by naloxone (10‐5m) while the effect of morphine on NANC contractions only was reduced to 67.6± 5.6% of the control contractions. It is suggested that morphine influences the excitatory neurotransmission via pre‐junctional sites, since morphine had no effect on the acetylcholine‐induced contractions.
Transmural distribution of left ventricular glucose uptake in spontaneously hypertensive rats during rest and exercise
Authors: LEIPÄLÄ J. A. , VIRTANEN P. , RUSKOAHO H. J. , HASSINEN I. E. , TAKALA T. E. S.
Published: December 2008

The transmural distribution of glucose uptake was studied in the left ventricle of 6‐month‐old male Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) during rest and swimming (20 min) using the 2‐deoxyglucose method. The baseline mean arterial pressure was 128 ± 8 (n= 8) in the WKY and 188 ± 22 mmHg (n= 8) in the SHR (P < 0.001). This pressure remained constant in the resting groups, whereas the product of mean arterial pressure and heart rate was initially 45×103± 3 times 103 and 63×103± 4×103 mmHg beats min‐1 in the swimming WKY and SHR and increased by 34–48×103 mmHg beats min‐1 during the swimming period. Total glucose uptake was 3.9 ± 1.2 μ mol min‐1 g‐1 protein in the resting WKY rats and 1.4 ± 0.4, μ mol min‐1 g‐1 protein (P < 0.001) in the swimming ones, the corresponding values for the resting and swimming SHR being 4.8 ± 1.4 μ mol min‐1 g‐1 protein and 3.2 ± 1.2 μmol min‐1 g‐1 protein (P < 0.01). Glucose uptake was 30% greater in the subendocardium (ENDO) of the resting WKY than in the subepicardium (EPI) (P < 0.01), but this gradient disappeared during swimming. Glucose uptake in the resting SHR was greatest in the middle layer of the ventricular wall, with no difference between ENDO and EPI, whereas during swimming the glucose uptake was distributed evenly across the left ventricular wall.

The blood lactate/pyruvate ratio increased only transitorily during the first minutes in the swimming SHR, while their plasma free fatty acid concentration was 1.2–1.3 mm initially and decreased by 32% (P < 0.01). The data show that both hypertension and acute exercise alter the transmural distribution of glucose uptake. Swimming caused a decrease in total left ventricular glucose uptake in both the WKY and SHR, which cannot be explained solely by an altered supply of competitive myocardial fuels.
Involvement of D1 dopamine receptors in the control of TSH secretion in the male rat
Authors: ANDERSSON K.
Published: December 2008

The effects of SCH 23390 (D1 dopamine receptor antagonist), SK&F 38393 (D1 dopamine receptor agonist), raclopride and remoxipride (D2 dopamine receptor antagonists) and ketanserin (5‐hydroxytryptamine 2 receptor antagonist) on TSH serum levels (radioimmunoassay) and on brain catecholamine levels (Falck‐Hillarp methodology in combination with quantitative histofluorimetry) were studied.

SCH 23390 produced a dose‐dependent increase in serum TSH levels in the lower dose range (0.01–0.03 mg kg‐1, i.p.) administered 30 min before decapitation and in the higher dose range (1.0–3.0 mg kg‐1) when given 2 h before decapitation. Following 30 min of treatment with the high doses of SCH 23390, reductions in serum TSH levels were found. The changes observed following SCH 23390 treatment occurred without affecting catecholamine levels in the median eminence and the peri‐ and paraventricular hypothalamic regions. Raclopride (0.1–10 mg kg‐1, i.p.), remoxipride (1.0 mg kg‐1, i.p.) or ketanserin (0.3 mg kg‐1, i.p.) changed neither serum TSH levels nor brain catecholamine levels. SK&F 38393 (1.0–10 mg kg‐1, i.p.) produced an increase in serum TSH levels.

The results suggest the existence of inhibitory and facilitatory mechanisms regulating TSH secretion mediated via D1 dopamine receptors.
Sympathetic transmission in small mesenteric arteries from the rat: highly calcium‐dependent at low stimulation rates
Authors: SJÖBLOM‐WIDFELDT N. , NILSSON H.
Published: December 2008

In the present study we examine the calcium requirements of the neurogenic responsein vitroof small arteries (150‐zoo am diameter) from the mesentery of Wistar rats. Intramural nerves were activated with electrical field stimulation. Responses to single impulses and to low‐frequency repeated stimulation were reduced or abolished by reducing the Ca2+concentration in the bathing solution from 2.5 to 1.0 mm. Responses to higher frequencies (16 Hz) were only slightly affected. Since calcium reduction had markedly less effect on responses to direct activation of the smooth muscle and on responses to any dose of exogenous noradrenaline, the calcium reduction had mainly pre‐junctional effects. The data show that part of the neurogenic response is highly calcium‐sensitive, perhaps more so than would be expected of a purely noradrenergic transmission.
Very rapid net transcapillary fluid absorption from skeletal muscle and skin in man during pronounced hypovolaemic circulatory stress
Authors: LÄNNE T. , LUNDVALL J.
Published: December 2008

High levels (110–120 cmH2O) of lower body negative pressure (LBNP) were used in male volunteers (n = 7) to produce pronounced hypovolaemic circulatory stress in an attempt to reveal the potential in man for compensatory absorption of extra vascular fluid from skeletal muscle and skin as studied in the upper arm by plethysmographic technique. LBNP evoked clear‐cut hypovolaemic symptoms or even accidental syncope as well as a marked tachycardiac response and a significant fall in systolic blood pressure. In the studied arm there was concomitantly a very rapid net transcapillary absorption of extravascular fluid into the circulation at an average rate of 0.35 ml min‐1 100 mr1 soft tissue during 5 min of LBNP exposure. These data demonstrate an amazingly great potential to increase plasma volume by ‘autotransfusion’ of fluid from tissue to blood, as may be visualized by extrapolation of the data from the arm to apply to the whole mass of skeletal muscle and skin in the body. The observed absorption rate would then correspond to a total fluid gain of no less than 700 ml within a period no longer than 5 min. At present, however, there is no evidence to indicate that such impressive fluid volumes can be rapidly transferred from the extra‐ to the intravascular space after actual blood loss.
Marked regional heterogeneity in blood flow within a single skeletal muscle at rest and during exercise hyperaemia in the rabbit
Authors: IVERSEN P. O. , STANDA M. , NICOLAYSEN G.
Published: December 2008

In 1985 both Pendergast et al. and Piiper et al. described a major regional heterogeneity in blood flow within single skeletal muscles both at rest and during exercise. Based on the microsphere method they described large variations in blood flow between muscle samples as large as 1 g each.

The aims of the present study were:

 To test this notion of regional heterogeneity in microsphere deposition within single skeletal muscles both at rest and during exercise.

 To compare the distribution of microspheres with other blood flow tracers.

 To test whether or not any heterogeneity was due to vasomotion in small arteries or arterioles.

Microspheres were infused into anaesthetized rabbits over either 10, 30 or 120 s, or 10 min. Exercise was mimicked by tetanic contractions obtained by electrical stimulation of the motor nerves. Three hindleg muscles were divided into samples of 0.25 g each. Regional heterogeneity was expressed as the coefficient of variation corrected for statistical distribution of microspheres (CVc). The CVc at rest was about 0.34. The CVc was unaffected by the various infusion periods and did not change during exercise. Simultaneous infusions of microspheres and 86Rb+ or antipyrine gave high correlations between the two blood flow tracers, with all r values exceeding 0.83 (n= 18).

We conclude that the microsphere method provides reliable estimates for regional blood flow within single skeletal muscles. The distribution of blood flow was markedly heterogeneous both at rest and during exercise. The heterogeneity in blood flow was apparently not a result of vasomotion.
Enzyme activities in type I and II muscle fibres of human skeletal muscle in relation to age and torque development
Authors: BORGES O. , ESSÉN‐GUSTAVSSON B.
Published: December 2008

The quadriceps muscles from 20–30‐ and 70‐year‐old clinically healthy men and women were studied regarding maximal isometric and isokinetic muscle torque in Newton metres (Nm), morphology and enzyme activity. Biopsy specimens were taken from the vastus lateralis muscle and freeze‐dried, and individual fibres were dissected out and identified as type I or type II. The activities of citrate synthase (CS), 3‐OHacyl‐coA dehydrogenase (HAD), lactate dehydrogenase (LDH), myokinase (MK) and creatine phosphokinase (CPK) were determined in pools of type I and type II fibres. In both age groups a higher oxidative (CS, HAD, 1.3–1.5 x) and a lower glycolytic (LDH, 0.7 x) capacity was found in type I than in type II fibres. The myokinase activity was higher in type II (2 x) than in type I, whereas CPK activity was similar. The young men showed higher CS activity in both type I and type II fibres (1.5 x) and higher CPK activity in type I fibres (1.4 x) than the young women. There were only minor changes in oxidative or glycolytic capacities in relation to age. Myokinase was the only enzyme that decreased markedly with age in both pools of fibre types. Type II fibre area and mean fibre area correlated significantly to muscle torque in both sexes. In men, myokinase activity in type II fibres was significantly correlated to type II fibre area and to maximal muscle torque.
Formation of inosine monophosphate (IMP) in human skeletal muscle during incremental dynamic exercise
Authors: SAHLIN K. , BROBERG S. , REN J. M.
Published: December 2008

The influence of exercise intensity on the accumulation of inosine monophosphate (IMP) in human skeletal muscle has been investigated. Ten men cycled at workloads corresponding to 40%, 75% and 100% of their maximal oxygen uptake (Vo2 max). Muscle IMP was below the detection limit (< 0.01 mmol kg‐1 dry wt) at rest and after exercise at 40% of Vo2 max, but increased to 0.26 ± 0.06(mean ± SEM) and 3.50 ± 0.51 mmol kg‐1 dry wt after exercise at 75% and 100% of Vo2 max respectively. Accumulation of IMP corresponded to a similar decrease in the total adenine nucleotide content. The muscle content of IMP was positively related to lactate and negatively related to phosphocreatine (PCr). IMP was formed in both fibre types, but the IMP content at fatigue was about twice as high in type II fibres as in type I fibres. It was concluded that the IMP content of human skeletal muscle is very low at rest and after low‐intensity exercise, but increases after moderate and high‐intensity exercise. In contrast to rat muscle, where deamination of AMP predominantly occurs in the fast‐twitch muscle fibres, IMP is formed during exercise in both fibre types in human muscle. Accumulation of IMP appears to reflect an imbalance between the rate of utilization and the rate of regeneration of ATP.