bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonatal breathing control mediated via the central chemoreceptors
Authors: WENNERGREN GÖRAN , WENNERGREN MARGARETA
Published: December 2008

Respiratory changes elicited via the central chemoreceptor system have been studied in anesthetized newborn guinea pigs and newborn rabbits. Periodic breathing was induced by inhibition of the central chemoreceptors by superfusion with alkaline cerebrospinal fluid. The periodic breathing was promptly reversed to steady by increasing the oxygen or carbon dioxide concentration in the inspired air or by intravenous theophylline. Elicitation of periodic breathing simply by exposing the animals to hypoxia succeeded only when very low oxygen concentrations were given. Clearcut respiratory excitation was produced by small amounts of theophylline applied onto the ventral surface of the medulla. Not only theophylline intravenously but also theophylline topically applied on the ventral medullary surface normalized spontaneously developed periodic breathing. Application of meperidine onto the ventral medullary surface gave respiratory inhibition with dosages considerably lower than required when given intravenously. The results emphasize the importance of an adequate respiratory drive from the central chemoreceptors for the maintenance of a regular breathing pattern. The findings support a view that at least part of the respiratory effects seen in the newborn following administration of meperidine or theophylline is due to effect of the drugs on the central chemosensitive system.
Vasoactive intestinal peptide evoked secretion of fluid and protein from rat salivary glands and the development of supersensitivity
Authors: EKSTRÖM JÖRGEN , MÅNSSON BENGT , TOBIN GUNNAR
Published: December 2008

Vasoactive intestinal peptide (VIP) injected intravenously was found to induce a flow of saliva from both the parotid and the submaxillary gland in the rat. The secretion was slow in onset. The amount of saliva secreted from the parotid gland was less than that from the submaxillary gland. Parotid saliva was very viscous. VIP‐evoked parotid saliva was more protein rich than both submaxillary saliva and saliva secreted in response to other sialagogue drugs including the β‐adrenergic receptor agonist isoprenaline. The effect of VIP was direct; it occurred after removal of the adrenals, after degeneration of intraglandular nerves and in the presence of autonomic blockers. A supersensitivity to VIP was demonstrable. In the parotid and the submaxillary glands the secretory response to VIP was enlarged following parasympathetic denervation and decentralization, respectively, while after sympathetic denervation supersensitivity was only found to develop in the submaxillary gland.
A model for quantitative sampling of myocardial venous blood in the pig
Authors: ANDERSEN FRANK R. , SEJERSTED OLE M. , ILEBEKK ARNFINN
Published: December 2008

A lack of good models for studies of myocardial metabolism prompted us to develop a model which allows the continuous measurement of myocardial blood flow and sampling of adequate amounts of coronary sinus (c. s.) blood without admixture of blood from the right atrium, with the working heart in situ. In the pig the left azygos vein drains into the c. s.and can easily be cannulated after thoracotomy. Thus, a shunt to the right atrium can be established by closing the entrance of the c. s.into the right atrium by a stitch ligature. More than 90% of shunt flow originates from the left ventricular myocardium. It is presently shown that establishing the shunt does not compromise myocardial flow, and there are no observable changes in left ventricular pressure, flow or dimensions. Myocardial flow in the drained and adjacent regions, as determined by injections of microspheres, and flow determined by electromagnetic flowmetry on the shunt are all identical. The model is stable during aortic constriction and isoproterenol infusion which induce expected changes in myocardial flow‐and oxygen consumption. Thus, the model described is suitable for hemodynamic and metabolic studies of the left ventricular myocardium with the working heart in situ.
Measurement of blood flow to the ventral prostate in the rat with radioactive microspheres: Effects of estradiol‐17β and human chorionic gonadotrophin
Authors: SELSTAM GUNNAR , DAMBER JAN‐ERIK
Published: December 2008

The function and size of the rat ventral prostate are stimulated by androgens and inhibited by estrogens. In order to test whether the blood flow in prostate is influenced in a similar fashion prostatic blood flow was measured after administration of human chorionic gonadotrophin (hCG) in rats with and without pretreatment of estradiol‐17β (E2) and in rats castrated for five days with and without treatment with E2. Prostatic blood flow was measured with the microsphere technique, which allows blood flow measurement without any interference with the organ. E2 treatment resulted in a decreased prostatic blood flow in both intact and castrated rats, and blood flow was restored to normal in intact rats after hCG‐injection. It was concluded that the E2 induced decrement of prostatic blood flow was at least in part mediated by a direct effect on the prostate.
Effect of sympathetic nerve stimulation and adrenoceptor blockade on pial arterial and venous calibre and on intracranial pressure in the cat
Authors: AUER L.M. , EDVINSSON L. , JOHANSSON B.B.
Published: December 2008

Pial arterial and venous calibre were continuously recorded through a closed cranial window preparation during cervical sympathetic nerve stimulation in 10 cats before and after alpha‐and beta‐adrenoceptor blockade. In addition, the intracranial pressure (ICP) was simultaneously recorded in 4 of the cats. Under resting conditions 33 arteries (mean diameter 130 μm) constricted by 11.7 ± 0.8% and 80 venous portions (mean diameter 152 μm) constricted by 13.7 ± 0.7% during sympathetic nerve stimulation. ICP decreased simultaneously by 16.5 ± 6.2%. Administration of the alpha‐adrenoceptor antagonist phenoxybenzamine i. v.(1.5 mg · kg‐1) abolished the reduction of ICP and markedly reduced, but did not completely abolish, the constrictor response of arteries and veins. The beta‐adrenoceptor antagonist propranolol (1.5 mg · kg‐1) did not significantly alter the reduction of ICP or the response of pial veins and small arteries, whereas the response of arteries with a diameter >150 μm was attenuated. It is concluded that the constriction of pial veins and arteries during sympathetic stimulation is mediated predominantly via alpha‐adrenoceptors. The sympathetic nerves of cerebral blood vessels may have stronger influence on the cerebral capacitance than on resistance vessels under normotensive and normocapnic conditions.
Cation exchange—a common mechanism in the storage and release of biogenic amines stored in granules (vesicles)?
Authors: UVNÄS BÖRJE , ÅBORG CARL‐HUGO
Published: December 2008

Studies on the uptake and storage of sodium and biogenic amines (phenylethylamine, noradrenaline, histamine) by two weak cation‐exchangers, IRC‐50 and Sephadex C‐50, and by biogenic granule‐enriched preparations demonstrated that the synthetic and biogenic materials had several common characteristics. They showed similar concentration‐and pH‐dependence and fitted the same cation‐exchange and receptor‐binding equations. The observations were taken to support the view that the matrices of amine‐storing granules have the properties of weak cation‐exchangers, with carboxyls as the cation‐binding groups.
Projected and receptive fields: A comparison of projected areas of sensations evoked by intraneural stimulation of mechanoreceptive units, and their innervation territories
Authors: SCHADY W.J.L. , TOREBJÖRK H.E.
Published: December 2008

Microneurography and intraneural microstimulation were employed in awake human subjects to study the characteristics of cutaneous mechanoreceptive units and the sensations mediated by them. 172 units innervating the hand and forearm were identified as either PC, RA (FA in hairy skin), SA I or SA II. Analysis of action potential waveforms in a sample of units suggests that most recordings were from within the myelin sheath. Receptive fields of RA and SA I units were significantly smaller than those of PC and SA II units and showed a proximodistal size gradient, which the latter two did not. The quality of sensations evoked by intraneural stimulation was determined by the type of unit activated, except in the case of SA II units, and their magnitude could be influenced by mechanical coactivation of other sensory units. As a rule projected fields of evoked sensations were larger the further away they were from the limb tip. This grading indicates that inputs from single mechanoreceptive units are processed differently according to their source and sensory submodality, possibly as a result of unequal “resolving powers” of the corresponding cortical neurons.
Cerebral localisation function from the input of single mechanoreceptive units in man
Authors: SCHADY W.J.L. , TOREBJÖRK H.E. , OCHOA J.L.
Published: December 2008

The accuracy of the cerebral localisation function from the input of single mechanoreceptive units was studied in the hand and forearm of human subjects by means of microneurography and intraneural microstimulation (INMS). The mean distance separating the projected field of a sensation evoked by INMS at liminal amplitude from the receptive field of the activated unit (interfield distance, or IFD) was found to vary from 2.6 mm for SA I units in the fingertips to 23.4 mm for SA I units in the forearm. A less pronounced proximodistal IFD gradient was found for quickly adapting units. IFD values for each skin region were comparable with those obtained by a point localisation test directly on the skin. This indicates that functional gradients exist for inputs from single mechanoreceptive units, and that stimulus localisation hardly improves when numerous units are coactivated.
Changes in diamine and polyamine metabolism in the duct‐ligated submaxillary and sublingual glands of the rat
Authors: EKSTRÖM JÖRGEN , ROSENGREN ELSA
Published: December 2008

Duct‐ligation of salivary glands is known to cause disappearance of acini, while ductal elements persist. In the present investigation the duct‐ligated submaxillary and sublingual glands increased in weight by 45–60% 3 days postoperatively, while they weighed 48–56 and 63–64% less than their contralateral glands 10 and 21 days postoperatively. In the duct‐ligated glands putrescine increased markedly both in terms of total amount and in terms of concentration, while spermidine and spermine decreased; histamine, in terms of concentration, was initially reduced but increased markedly later. As to total amount histamine tended to increase along time. The histamine‐forming enzyme, histidine decarboxylase, and the putrescine‐forming enzyme, ornithine decarboxylase, showed higher activities in the duct‐ligated submaxillary glands than in the contralateral glands. Di‐and polyamines and their synthesizing enzymes are considered to increase in growing tissue. The present results of increased amine levels and enzyme activities are discussed in relation to previous findings of ductal goblet cell hyperplasia following duct‐ligation and of increases of polyamines in cystic fibrosis.
Renal blood flow during unilateral ureteral obstruction: Effects of reduced perfusion pressure, acetylcholine, and thromboxane A2blockers in obstructed and unobstructed rat kidneys
Authors: HOPE A. , CLAUSEN G.
Published: December 2008

Renal blood flow (RBF) is markedly reduced in kidneys with unilateral ureteral obstruction (UUO), possibly due to vascular constriction. Whether obstructive nephropathy is associated with impaired RBF autoregulation is unknown. We therefore investigated RBF autoregulation in obstructed and contralateral unobstructed rat kidneys during and following release of 24 h and 6 days of UUO, using stepwise reduction of renal arterial pressure and electromagnetic recording of RBF. The lower pressure limit of autoregulation was increased and the maximal vasodilatory ability in response to infusion of acetylcholine into the renal artery was reduced only in the unobstructed kidney at 24 h of UUO. Thus, we conclude that the vasodilatory reactions to both these maneuvres, previously observed to be markedly reduced during acutely elevated ureteral pressure (Hope & Clausen 1982), were reestablished: In the obstructed kidneys in less than 24 h (RBF ˜70% of control) and in the contralateral unobstructed kidneys in less than 6 days (RBF ˜140% of control). Infusion of the thromboxane A2(TXA) synthetase inhibitors imidazole and 3‐ethyl pyridine in controls and at 24 h and 6 days of UUO did not produce renal vasodilation. These results do not support the suggestion that TXA contributes directly to the increase in renal vascular resistance observed during or following release of UUO in the rat.
Cortical magnification factor and contrast sensitivity to luminance‐modulated chromatic gratings
Authors: ROVAMO JYRKI
Published: December 2008

Contrast sensitivity to luminance‐modulated blue, green, red, and neutral gratings was measured at different spatial frequencies and eccentricities within 0–86 deg in the temporal visual field. Contrast sensitivity to gratings of constant area and spatial frequency was independent of wavelength composition but decreased with increasing eccentricity. When the gratings were scaled by the magnification factor of the human striate cortex to produce cortically similar stimulus conditions at different eccentricities (M‐scaling), contrast sensitivities became independent of visual field location irrespective of grating colour. Using colour naming we found, in accordance with previous studies, that hue changed and saturation decreased when the eccentricity of a constant‐size grating field increased. In contrast, the hue and saturation of M‐scaled grating fields were independent of eccentricity. The results suggest that the effects of eccentricity on photopic colour vision can largely be counteracted by M‐scaling which adjusts the spatial aspects of stimuli with respect to the decrease in ganglion cell density and increase in receptive field size towards the periphery of the visual field.
Compensatory cardiac mechanisms evoked by acute occlusion of the right coronary artery in dogs
Authors: GEIRAN ODD , MOLAUG MÅLFRID , KIIL FREDRIK
Published: December 2008

The cardiac response to intermittent occlusion of the right coronary artery was examined in anesthetized open‐chest dogs at different levels of blood volume. The reduction in stroke volume averaged 15±2% and was related to the extent of the ischemic area (r=0.72), which comprised 45–70% of the free wall of the right ventricle. Ultrasonic recordings of segment lengths showed end‐diastolic distention and activation of the Frank‐Starling mechanism in the uninjured parts of the free wall. The transseptal end‐diastolic pressure difference was abolished, suggesting movement of the interventricular septum to the left. Nevertheless, the relationship between stroke volume and left ventricular end‐diastolic pressure (left ventricular function curve) as well as the relationship between stroke volume and the end‐diastolic segment length of the left ventricular free wall were unaltered. Comparisons of data obtained at similar stroke volume showed activation of the Frank‐Starling mechanism in the interventricular septum which may compensate for the negative effect of a change in its position.
Vascular permeability changes and smooth muscle contraction in relation to capsaicin‐sensitive substance P afferents in the guinea‐pig
Authors: LUNDBERG JAN M. , BRODIN ERNST , HUA XIAOYING , SARIA ALOIS
Published: December 2008

The occurrence of neurogenic inflammation as indicated by Evans blue extravasation was studied in various organs of the guinea‐pig. Electrical stimulation of the trigeminal nerve caused Evans blue extravasation due to increased vascular permeability in the nasal mucosa and gingiva. Vagal stimulation induced extravasation in the epiglottis, larynx, trachea, bronchial tree and esophagus. Splanchnic stimulation induced Evans blue extravasation in the gall bladder, bile ducts and superior mesenteric artery. Stimulation of the inferior mesenteric ganglion caused a marked extravasation in the upper and middle part of both ureters, while pelvic activation induced a reaction in the lower ureter, urinary bladder, urethra and vagina. I.v. substance P (SP) (3 nmolxkg11) or capsaicin (1 μmol × kg‐1) both induced extravasation in many tissues including those in which nerve stimulation produced a response. The extravasation responses to SP, capsaicin or nerve stimulation all had similar border‐line zones, such as esophagus to stomach, bile ducts to duodenum, rectum to anal mucosa, pulmonary artery to heart and vagina to uterus. Quantitative determinations showed especially large permeability effects in the trachea, umbilical ligament and ureter. The permeability effect of capsaicin and nerve stimulation was abolished in capsaicin‐pretreated animals, while the response to SP was still present. Capsaicin pretreatment caused an almost total loss of SP in several visceral organs including the respiratory and urinary tracts. The SP content in these tissues was correlated (r=0.97) to the Evans blue extravasation following nerve stimulation or i.v. capsaicin. SP and capsaicin caused contractions in vitro of the esophagus, ureter, urinary bladder, trachea and gall bladder. The capsaicin‐induced contraction of the trachea was resistant to tetrodotoxin pretreatment. The non‐cholinergic, non‐adrenergic contraction of the urinary bladder upon field stimulation was still present in capsaicin‐pretreated animals. In conclusion, neurogenic inflammation occurs in several organs with a highly region‐specific distribution, which is accompanied by the presence of capsaicin‐sensitive SP neurons. Both parasympathetic and sympathetic pathways contain capsaicin‐sensitive afferent fibres which mediate an increase in vascular permeability most likely by releasing SP. In addition, both capsaicin and SP cause smooth muscle contraction in several visceral organs.
The uptake of 5‐hydroxytryptamine in endothelial cells cultured from the pulmonary artery in rats: A cytochemical study
Authors: KJELLSTRÖM THOMAS , AHLMAN HÅKAN , DAHLSTRÖM ANNICA , HANSSON GORAN K. , RISBERG BO
Published: December 2008

Endothelial cells from the rat pulmonary artery were cultured and identified ultrastructurally and immunocytochemically by the presence of factor VIII antigens. Monolayers of cultured cells were treated according to the Hillarp‐Falck technique and studied cytofluorimetrically to estimate intracellular serotonin (5‐HT) levels. An uptake of 5‐HT from the incubation medium was demonstrated at a concentration of 10‐3M. However, after inhibition of monoamine oxidase (nalamide 5 × 10‐4M) to prevent intracellular degradation of the amine an uptake could be demonstrated at 10‐5M. The amine uptake into endothelial cells utilizes an active pumpmechanism, since it was effectively antagonized by either imipramine (10‐4M) or ouabain (10‐5M). These in vitro findings contrast earlier cytofluorimetric in vivo studies, where 5‐HT uptake predominantly occurred in interstitial mast cells.
Evidence for bicarbonate‐dependent lithium reabsorption in dog kidneys
Authors: HARTMANN ANDERS , HOLDAAS HALLVARD , STEEN PETTER A. , KIIL FREDRIK
Published: December 2008

To examine whether lithium is reabsorbed along a transcellular or a paracellular route, experiments were performed in anesthetized volume‐expanded dogs under conditions of constant glomerular filtration rate (GFR). Ouabain, in doses inhibiting about 80 % of Na,K‐ATPase, and ethacrynic acid, another inhibitor of transcellular NaCl reabsorption, did not inhibit lithium or bicarbonate reabsorption. Lithium reabsorption increased in proportion to plasma concentration of lithium (PLi) up to 12 mM, suggesting a passive transport of lithium. During ouabain administration acetazolamide halved bicarbonate reabsorption, the main driving force for paracellular reabsorption, and halved the reabsorption of lithium. The reabsorbate concentration of lithium, calculated from data obtained before and after acetazolamide infusion, was almost equal to PLi. Mannitol, which reduces paracellular osmotic transport without affecting bicarbonate reabsorption, reduced lithium and chloride reabsorption in the same proportion as acetazolamide (r=0.87). Combined acetazolamide and mannitol administration reduced fractional lithium reabsorption to 0.09±0.02. These data indicate that lithium is not actively transported but reabsorbed passively along a paracellular route by osmotic forces provided by transcellular NaHCO3reabsorption.
Renal sympathetic activity in spontaneously hypertensive rats and normotensive controls, as studied by three different methods
Authors: LUNDIN S. , RICKSTEN S.‐E. , THORÉN P.
Published: December 2008

Recordings of sympathetic activity from multifibre preparations of renal nerves have produced conflicting results concerning the presence or absence of an increased sympathetic discharge in spontaneously hypertensive rats (SHR) compared to normotensive Wistar‐Kyoto rats (WKY). Therefore, recordings of single fibre activity to the kidney were performed in anesthetized SHR and WKY in comparison with multifibre recordings in conscious, undisturbed rats. A new method of estimating sympathetic discharge by analyzing the variability of “cycle activity” in multifibre nerve recordings was also used. The average nerve activity in a great number of cardiac cycles was then expressed in relation (in per cent) to the nerve activity in a small number of cardiac cycles with the highest and lowest nerve activity in each rat. Single fibre recordings showed a significantly higer sympathetic activity to the kidneys in SHR (3.8±0.3Hz) than in WKY (1.7±0.2Hz; p<0.001). Also average “cycle activity” was significantly higher in conscious SHR (34±1%) than in WKY (26±2%, p<0.01). This was due to the larger number of cardiac cycles in SHR with high sympathetic activity while WKY showed more of “silent” cardiac cycles which lacked nerve impulses. Further, the recordings of rectified multifibre renal nerve activity also showed an elevated sympathetic activity in conscious SHR rats. The increased renal sympathetic activity appears to reflect the “primary” central nervous “hyperreactivity” characterizing SHR hypertension. It is suggested that the increased renal sympathetic activity may be of particular importance for the development of primary hypertension in SHR and perhaps also in man.
Interaction between “mental stress” and baroreceptor reflexes concerning effects on heart rate, mean arterial pressure and renal sympathetic activity in conscious spontaneously hypertensive rats
Authors: LUNDIN S. , RICKSTEN S.‐E. , THORÉN P.
Published: December 2008

Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were compared concerning the interactions between cortico‐hypothalamic alerting responses and baroreflex influences on neurogenic cardiovascular control. For this purpose mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were continuously recorded during night time in conscious, otherwise undisturbed rats. Baroreceptor sensitivity was assessed as percentage HR and RSNA reductions per mmHg MAP elevation when a standardized phenylephrine infusion was performed. A state of acute “mental stress” could be induced by a likewise standardized sudden blowing of air. These two opposing influences on neurogenic cardiovascular control were also experimentally superimposed in various ways and the effects on MAP, HR and RSNA followed. During “rest” RSNA was higher in SHR than in WKY and it also increased more during “mental stress”. The baroreflex sensitivity was clearly reduced in SHR and WKY concerning HR reduction (0.44±0.06 vs. 0.78±0.08%/mmHg; p<0.01) but not so concerning RSNA, which was similar in SHR and WKY (2.6±0.2 vs. 2.9±0.4%/mmHg). If expressed (HR + 1±3%; p<0.025 vs. SHR and RSNA + 11%±10, p<0.01 vs. SHR). These results) (0.10±0.02 vs. 0.06±0.01 μV/mmHg; p<0.12). Also single fibre recordings in anaesthetized rats showed the same principle difference between SHR and WKY. Addition of “mental stress” during phenylephrine baroreflex activation clearly increased both HR (24±7%) and RSNA (114±21 %) in SHR, while almost no change then occurred in WKY (HR + 1±3%; p<0.025 vs. SHR and RSNA + 11%±10, p<0.01 vs. SHR). These results suggest that a modestly accentuated cortico‐hypothalamic activity ordinarily prevails in SHR, explaining the suppressed baroreflex control of heart rate and the augmented sympathetic activity to e.g. renal and splanchnic areas. Further, environmental alerting stimuli induce in SHR more powerful defence reactions which, unlike the situation in WKY, readily overcome baroreflex inhibitory influences on sympathetic activity.
Renal interstitial volume of the rat kidney
Authors: LARSON M. , SJÖQUIST M. , WOLGAST M.
Published: December 2008

The intravascular plasma volume and the interstitial volume of the rat kidney were determined by an indicator dilution method with a bolus injection of 125‐I‐labelled human serum albumin and 51‐Cr‐EDTA into the renal artery and subsequent recording of the indicator‐dilution curves in the venous effluent, sampled at intervals of 0.33s. The curves allowed determination of both the mean transit time of the two indicators and total renal plasma flow. The volumes of distribution were obtained by multiplying these two factors. Under control conditions the plasma volume was 93.0±11.2μl/100g rat (mean±SE), which is 17.9% of the total kidney volume. The interstitial volume was 68.3±8.6μl/100g, corresponding to 13.1% of the total kidney volume. During expansion with 0.15 M NaCl, 10% of body weight, the plasma and interstitial volumes were not significantly increased. The values for the two volumes were 101.6±9.7 and 72.8±6.8 μl/100g, respectively. The kidney weight showed, in contrast a clear increase from 539 to 670mg/100g, reflecting the expansion of the proximal and distal tubules due to the increased glomerular filtration rate. It is concluded that although the saline load produced a rise in the renal interstitial pressure, the expected expansion of the interstitium became small, due to the parallel expansion of both the vascular and tubular systems which compress the renal interstitium.
Lysosomal changes related to exercise injuries and training‐induced protection in mouse skeletal muscle
Authors: SALMINEN A. , HONGISTO K. , VIHKO V.
Published: December 2008

Three experiments were designed to study the lysosomal changes associated with the development and maintenance of the endurance training induced resistance against exercise injuries in mouse skeletal muscles. The activities of arylsulphatase, cathepsin C, cathepsin D, and β‐glucuronidase were assayed from the red part of mouse quadriceps femoris muscle 4 days after prolonged strenuous running of 4–9 h duration. Exercise injuries were characterized by necrotic fibers and focal inflammation. Strenuous running of untrained mice induced necrotic lesions and a 4–5 fold increase in the activities of lysosomal enzymes. This lysosomal response was considerably reduced already by daily training bouts on the 3 days preceding the strenuous exertion. Simultaneously exercise injuries were markedly reduced. Extending the endurance training program increased the running ability of mice and further reduced the necrotic lesions and lysosomal changes induced by the strenuous exercise. The detraining of 1 week after the termination of regular endurance training considerably increased the degree of exercise induced lysosomal response. The detraining of longer durations further increased the lysosomal response and no effect of prior endurance training existed after 1 month detraining. Our observations suggest that the severity of exercise injuries is related to the strength of the exercise stimulus and the level of preceding physical activity and can be characterized by the lysosomal changes.
Interaction of substance P with dispersed pancreatic acinar cells from the guinea pig
Authors: SJÖDIN LARS , BRODIN ERNST , SRIVASTAVA GIRISH
Published: December 2008

Binding of 125I‐[Tyr8]‐SP to isolated pancreatic acinar cells was inhibited in a concentration‐dependent way by SP, [Tyr8]‐SP and longer C‐terminal fragments of SP. SP6–11 was the shortest sequence to bind significantly to SP‐receptors as well as to stimulate amylase release from dispersed pancreatic acini. SP7–11 and shorter fragments did not inhibit binding of 125I‐[Tyr8]‐SP and did not stimulate secretion of amylase significantly. SP augmented the stimulatory effect of cholecystokinin on amylase release. Two SP‐antagonists, [D‐Pro2, D‐Trp7, 9]‐SP and [D‐Pro2, 4, D‐Lys3, D‐Gln5, 6, D‐Trp7, 9]‐SP inhibited binding of 125I‐[Tyr8]‐SP in a concentration dependent manner and tended at a high concentration to reduce release of amylase evoked by submaximal concentrations of SP.
Effects of the substance P antagonist (D‐Arg1, D‐Pro2, D‐Trp7, 9, Leu11)‐SP on the miotic response to substance P, antidromic trigeminal nerve stimulation, capsaicin, prostaglandin E1, compound 48/80 and histamine
Authors: MANDAHL AGNETA , BILL ANDERS
Published: December 2008

The effects of the substance P analogue (D‐Arg1, D‐Pro2, D‐Trp7, 9, Leu11)‐SP on the ocular inflammatory responses (miosis, vasodilation, protein leakage into the aqueous humour and eye pressure rise) to antidromic trigeminal nerve stimulation (trigeminal stimulation), intracameral injections of substance P (SP), capsaicin, prostaglandin E1 (PGE1), compound 48/80 and histamine were investigated in albino rabbits. The effects of nerve blockade with tetrodotoxin and blockade of histamine receptors on the responses to compound 48/80 and histamine were also investigated. Histamine H, receptors were blocked with clemastin and H2 receptors with cimetidin. Formation of endogenous prostaglandins was prevented with indomethacin. The pupil size and the eye pressure were measured. The aqueous humour was collected immediately after the animal was killed, and analyzed for protein concentration. (D‐Arg1, D‐Pro2, D‐Trp7, 9, Leu11)‐SP had no significant miotic effect, but tended to cause a break‐down of the blood‐aqueous barrier. Miosis caused by SP, trigeminal stimulation, capsaicin, PGE1, compound 48/80 or histamine was blocked by (D‐Arg1, D‐Pro2, D‐Trp7, 9, Leu11)‐SP. Histamine miosis was significantly reduced by blockade of nerve conduction or histamine receptors, while miosis caused by compound 48/80 was not. Nerve blockade abolished the rise in intraocular pressure caused by compound 48/80. Our results indicate that (D‐Arg1, D‐Pro2, D‐Trp7, 9, Leu11)‐SP is a specific SP blocker in the sphincter pupillae muscle. They are strong evidence for the hypothesis that trigeminal stimulation and capsaicin cause miosis by release of SP or a related substance (SPLI), and it seems likely that the miosis caused by PGE1 and compound 48/80 is also caused by SPLI release. Histamine miosis is probably mediated both by SP receptors and histamine receptors in the pupillary sphincter muscle.
Effects on aggregation of human platelets of two xanthines and their interactions with adenosine
Authors: VINGE ELLEN , ANDERSSON KARL‐ERIK , PERSSON CARL G. A.
Published: December 2008

Adenosine receptor antagonism has been suggested to be the cellular basis for many extrapulmonary actions of xanthine derivatives, such as theophylline. Enprofylline (3‐propylxanthine) is a poor adenosine antagonist but is five times as potent as theophylline as a bronchodilator in man. Adenosine is a potent inhibitor of platelet aggregation, but also xanthines are considered to exert this action. In the present study, effects of theophylline and enprofylline on ADP‐induced aggregation of human platelets were studied in vitro. Theophylline alone in concentrations exceeding 280 μM inhibited platelet aggregation concentration‐dependently. Enprofylline alone mimicked this effect but was about five times more potent than theophylline. At the lowest concentrations used, corresponding to upper therapeutic levels, neither of the two xanthines affected platelet aggregation by ADP. The interactions between these low concentrations of the xanthines and adenosine were then evaluated. In the presence of theophylline 110 μM the inhibitory effect of adenosine 4 μM was attenuated, whereas the presence of enprofylline 21 μM enforced the inhibitory effect of adenosine. Thus, at low concentrations where neither theophylline nor enprofylline inhibits platelet aggregation theophylline antagonizes the antiaggregatory effect of adenosine, whereas enprofylline acts in synergy with this nucleoside.
Adrenergic effects on plasma levels of glucagon, insulin, glucose and free fatty acids in rabbits—influences of selective blocking drugs
Authors: KNUDTZON JØRGEN
Published: December 2008

Species differences concerning the effects of alpha‐and beta‐receptor stimulation on glucagon release and carbohydrate metabolism have been reported. The aim of the present study was to investigate how the subtypes of alpha‐and beta‐receptors regulate the plasma levels of glucagon, insulin, glucose and free fatty acids in fasted rabbits. Epinephrine‐induced 1) hyperglucagonaemia, 2) hypoinsulinaemia and 3) hyperglycaemia were significantly inhibited by alpha‐2 receptor blockade (yohimbine), and not influenced by alpha‐1 receptor blockade (prazosin). Isoproterenol‐induced 1) hyperglucagonaemia was not affected by beta‐1 or beta‐2 receptor blockade, 2) hyperinsulinaemia was inhibited by a lower dose of beta‐2 (ICI 118.551) than beta‐1 receptor blockade (metoprolol), 3) hyperglycaemia was inhibited by beta‐2 receptor blockade and 4) increases in the plasma levels of free fatty acids were blocked by beta‐1 receptor blockade. It is concluded that in fasted rabbits: 1) plasma levels of glucagon are mainly increased by alpha‐2 receptor stimulation, 2) plasma levels of insulin are decreased by alpha‐2 receptor stimulation, and increased more by beta‐2 than by beta‐1 receptor stimulation, 3) plasma levels of glucose are increased by alpha‐2 and beta‐2 receptor stimulation and 4) the plasma levels of free fatty acids are increased by beta‐1 receptor stimulation.
The effect of dorsal root transection on the efferent motor pattern in the cat's hindlimb during locomotion
Authors: GRILLNER STEN , ZANGGER PETER
Published: December 2008

Mesencephalic cats can walk on a treadmill if the midbrain locomotor region is stimulated. The motor pattern of different hindlimb muscles is similar to that of the intact cat. The present experiments in the mesencephalic preparation test if the complex motor pattern in one hindlimb is causally dependent on the afferent signals arising in the same limb during walking. The electromyographical activity and the movement pattern during locomotion were compared before and after transecting all dorsal root fibres originating from one hindlimb. Flexor and extensor muscles at different joints may retain their general pattern after the dorsal root transection. This applies also to muscles such as the knee flexors, which have a short and early flexor burst and a second burst during the extension phase, and the short toe dorsiflexor, which has an early burst in the transition between flexor and extensor activity. After the dorsal root transection the pattern of activity may become more variable and it can even break down altogether. The present results demonstrate that the central nervous system devoid of phasic afferent inflow from one hindlimb can produce a complex motor output to this limb rather than a motor pattern degraded to a simple alternation between flexors and extensors.
Influence of Ca2+ on the voltage dependent mechanosensitivity of the hair cells in the lateral line organs of Xenopus laevis
Authors: JØRGENSEN FINN
Published: December 2008

The influence of the transepithelial voltage (Vt) on the degree of synchronization (DOS) of afferent spikes from lateral line organs to mechanical stimulation has been examined in the isolated voltage clamped skin of Xenopus laevis. With 1 mM CaCl2, 5 mM MOPS‐KOH (pH = 7.1) in the apical solution and Ringer's solution on the serosal side of the skin, changes in Vt from ‐60 mV to 65 mV (inside relative to outside) lead to a nonlinear reduction in DOS to a minimum value, where the afferent spikes were no longer time‐locked. Beyond this value of Vt, DOS increased until at Vt= 100–120 mV DOS was again reduced. The reduction of DOS to the minimum value was associated with a monotonic increase in the mean phase of DOS, which abruptly changed approximately 180° as the minimum was passed. Change in the apical Ca2+ concentration from 0.1 mM to 10 mM increased the Vt at which the minimum value was attained, by 39 mV. The voltage dependency of DOS is in agreement with a model where the driving force for the receptor current across the apical membrane of the hair cells controls the generation of time‐locked afferent spikes to mechanical stimulation. The Vt, at which the minimum value of DOS was attained, is then equivalent to the reversal potential across the apical membrane. The influence of the apical Ca2+ concentration on this V, may be caused by the change in the gradient of Ca2+ or change in the ionic selectivity of the transduction channels.
Skeletal muscle sympathetic activity at rest in trained and untrained subjects
Authors: SVEDENHAG JAN , WALLIN B. GUNNAR , SUNDLÖF GÖRAN , HENRIKSSON JAN
Published: December 2008

The effect of physical training on muscle sympathetic activity (MSA) was studied by comparing resting levels of MSA in 8 well‐trained racing cyclists and in 8 age‐matched untrained subjects (mean age 22 yrs). In addition, MSA was determined for 5 untrained subjects before and after an 8‐week training program on cycle erogmeters (training group). Recordings were made from the peroneal nerve at the knee with the subject in recumbent position. The well‐trained cyclists were characterized by a clearly higher maximal oxygen uptake (VO2 max) and lower heart rate at submaximal exercise (180 W) than their untrained counterparts. These variables were also significantly changed with training in the training group. In contrast, there were no training‐related effects on MSA. Thus, MSA expressed as either the number of sympathetic bursts/100 heart beats (+2%, NS) or bursts/min (‐10%, NS) did not differ between the well‐trained cyclists and the untrained controls. Furthermore, no changes in MSA occurred with training in the training group (bursts/100 heart beats: +8%, NS; bursts/min ‐2%, NS). Individual variations in MSA were large and independent of training state. It is concluded that differences in physical conditioning do not account for the large inter‐individual differences in MSA in resting man.
Influence of antimuscarinics on alpha‐adrenoceptors in the female rabbit urethra
Authors: LARSSON BENGT , ANDERSSON KARL‐ERIK , MATTIASSON ANDERS
Published: December 2008

The effects of the tertiary amine atropine and its structural analogues homatropine and scopolamine, as well as the quarternary amine emeprone, were evaluated on noradrenaline (NA)‐induced contractions of isolated female rabbit urethral ring preparations. In addition, the abilities of these antimuscarinics to inhibit3H—dihydro—alpha—ergocryptine (3H—DHE) binding to alpha—adrenoceptors were studied on a crude membrane preparation from the female rabbit bladder base and urethra. Atropine and homatropine depressed the NA‐ induced contractions in a concentration‐dependent way, whereas this was not seen with scopolamine. Emeprone 10‐510‐4M augmented the contractions, an effect possibly attributable to a NA‐uptake blocking effect. All antimuscarinics displaced specific3H— DHE binding, the order of potency being atropine>homatropine>emeprone>scopolamine. In general a good correlation was seen between the binding and mechanical activity studies for atropine, homatropine and scopolamine, while this was not found for emeprone. It is concluded that alpha‐adrenoceptor blockade by atropine can be observed at concentrations exceeding 10‐7M. Scopolamine, showing alpha‐adrenoceptor blocking properties only in high concentrations, may be used as an alternative for blockade of muscarinic cholinoceptors.
Effects of some α‐adrenoceptor stimulating and blocking agents on the salivary amylase secretion in the rabbit
Authors: GJÖRSTRUP PER
Published: December 2008

In rabbits under urethane anaesthesia parotid secretion of fluid and amylase in response to electrical stimulation of the sympathetic and parasympathetic nerves was measured before and after injections of various agents acting on α‐adrenoceptors. Amylase secretion in response to sympathetic nerve stimulation at 0.5 and 1 Hz was markedly reduced by clonidine, 0.5–30 μg/kg, in a dose related manner. The effect was not due to an altered responsiveness of the gland, since isoprenaline still caused a large release of amylase. Phenylephrine, 10 μg/kg, and prazosine, 300 μg/kg, had no effect on the sympathetically evoked amylase secretion. Yohimbine in a dose of 0.5 mg/kg increased the amylase output in response to sympathetic nerve stimulation at 0.5 Hz by 70%, while the response at 1 Hz, which is close to maximum for the gland, was not significantly increased. The fluid and amylase secretion produced by parasympathetic nerve stimulation at 1.5, 5.0 and 10 Hz remained unchanged after clonidine, 1.0–30 μg/kg, or yohimbine 0.5 mg/kg. In rabbits provided with chronic parotid fistulae fluid and amylase secretion were studied after injections of clonidine, 30 μg/kg, and yohimbine, 1 mg/kg. In the conscious animal clonidine reduced not only amylase but also fluid secretion, by around 50 and 30%, respectively, indicating an effect on the activity in both the sympathetic and parasympathetic secretory nerves. Yohimbine increased the output of amylase during feeding, seen as an increased mean output of amylase due to an increased concentration of amylase in the saliva, while fluid secretion remained unchanged. The various experiments suggest that amylase secretion in response to sympathetic activation may be influenced by prejunctional control of transmitter release via α‐2‐adrenoceptors, and that this control may be of physiological significance. Parasympathetically evoked secretion does not seem to be under the influence of a similar control.
Functional development of the visual system in normal and protein deprived rats
Authors: SJÖSTRÖM A. , CONRADI N. G. , ANDERSSON S. A.
Published: December 2008

During an investigation focused on development of visual evoked responses (VER) in normal and protein deprived rats indications of persisting latency differences were found. Since such differences are in variance with previous reports special attention was paid to compare control and protein deprived adult rats. Protein deprivation was induced by feeding rats a diet with 50% reduction in protein content compared with control rat diet from two weeks before onset of gestation until examination. Dependence on experimental variables of latencies and complexity of the VER illustrated the need of a well defined experimental situation. Adult protein deprived rats showed significantly longer latencies to onset and to the first three peaks of the VER and an altered complexity of the response. It is suggested that the observed alterations result from effects of the protein deprivation on early brain development since this and previous studies have shown similar alterations in developing young rats. The divergence in findings between the present and previous reports may be explained by differences in degree of malnutrition and in other experimental conditions.
Spontaneous running in wheels. A microprocessor assisted method for measuring physiological parameters during exercise in rodents
Authors: SHYU B. C. , ANDERSSON S. A. , THORÉN P.
Published: December 2008

When examining physiological parameters during exercise in rodents most techniques use forced exercise on treadmills or forced swimming which undoubtedly will employ stress to the animals. This paper describes a convenient method to measure physiological parameters during spontaneous exercise in rodents. Hamsters and rats develop a spontaneous running pattern in wheels. The hamsters are reaching maximal activity almost immediately. In contrast, rats increase their running activity with time and need about 4 weeks to reach an average of about 7 km/day. The amount of running is measured by a microprocessor system. With this technique pain threshold, blood pressure and heart rate for example could be measured for extended periods of time, without changing the environment of the animals.
Microsphere analysis of β2‐adrenergic control of resistance in different vascular areas after hemorrhage
Authors: GUSTAFSSON DAVID , ANDERSSON LENA , MÅRTENSSON LENA , LUNDVALL JAN
Published: December 2008

In cats exposed to bleeding (exsanguination of 15 ml×kg bwt‐1) the microsphere technique was used to determine regional vascular resistances in a large number of tissues before and after i.v. administration of the ‘selective’β2‐adrenoceptor antagonist ICI 118,551. β2‐blockade significantly raised vascular resistance in the stomach (+26%), small (+25%) and large (+38%) intestine, pancreas (+29%), kidney (+39%), omental (+33%) and subcutaneous (+26%) fat, ‘white’ skeletal muscle (+19%), and skin (+24%). These findings indicate that, with intact β‐adrenoceptors, β2‐adrenergic dilator interaction counteracted the hemorrhage evoked vasoconstrictor influences. β2‐blockade also evoked quite a strong increase of total peripheral resistance (19%) and led to some redistribution of cardiac output. It is concluded that β2‐adrenergic inhibition of vascular tone significantly seems to improve tissue perfusion during bleeding in several vascular areas. Such effects may be of special significance during severe hemorrhage. In the intestine, pancreas, and adipose tissue, for example, protection against excessive vasoconstriction may serve to minimize the severe metabolic disturbances with secondary release of toxic factors into the circulation reported during hemorrhagic shock.
Theophylline antagonizes cardiovascular responses to dipyridamole in man without affecting increases in plasma adenosine
Authors: SOLLEVI ALF , ÖSTERGREN JAN , FAGRELL BENGT , HJEMDAHL PAUL
Published: December 2008

Effects of the vasodilator dipyridamole (Dip) on plasma adenosine levels, heart rate, blood pressure and skin microcirculation were studied in 13 healthy male volunteers. Venous plasma concentrations of adenosine, catecholamines, dipyridamole and theophylline were determined by HPLC. Skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy in the finger nailfold. The adenosine uptake inhibitor Dip (approximately 1–3 μM in plasma) increased plasma adenosine from 0.15±0.03 to 0.29±0.03 μM (p<0.01) and heart rate (HR) by 13±2 beats/min (p<0.01) and reduced diastolic blood pressure by 6±2 mmHg (p<0.05). Dip did not significantly affect the skin circulation since basal CBV, digital pulse amplitude (DAPA), skin temperature and post‐occlusive reactive hyperemia were unchanged. Plasma catecholamine levels were also unaffected. The adenosine receptor antagonist theophylline (45–55 μM in plasma) did not influence basal plasma catecholamine or adenosine levels, HR, blood pressure or skin microcirculation. Following theophylline Dip caused similar elevations of plasma adenosine but no changes in HR or blood pressures. Our results support the hypotheses that Dip dilates blood vessels in man by elevating endogenous adenosine and that theophylline acts as an adenosine antagonist. Under basal conditions, the skin microcirculation appears to be regulated mainly by factors other than adenosine.