bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of liver ischemia on degradation of different classes of hepatic proteins
Authors: FORNANDER JÖRGEN , HASSELGREN P. O. , JAGENBURG RUDOLF
Published: December 2008

The effects of liver ischemia on hepatic protein degradation were studied in rats. In one series of experiments degradation was measured in incubated liver slices as release of trichloroacetic acid soluble radioactivity from proteins prelabelled with L‐(14C)‐leucine during 4 h (short‐lived proteins) or during 24 h (long‐lived proteins). In another series of experiments protein degradation was determined in vivo by measuring decay of radioactivity in hepatic proteins prelabelled with (14C)‐sodium bicarbonate administered intraperitoneally 4 h or 24 h before induction of liver ischemia. Degradation of short‐lived proteins was reduced by 50% both in vitro and in vivo during liver ischemia while breakdown of long‐lived proteins was unchanged. Thus, short‐lived and long‐lived proteins were differently affected by liver ischemia. These results are consistent with the concept of distinct proteolytic pathways for different classes of proteins.
Breathing pattern and lung volumes during exercise
Authors: LIND F. , HESSER C. M.
Published: December 2008

The interrelationships of ventilation (V˙), tidal volume (VT), inspiratory (TI), expiratory (TE) and total breath (Ttot) durations, mean inspiratory (VT/TI) and expiratory (VT/TE) flows, and lung volumes were studied in normal subjects at rest and during exercise on a cycle ergometer. The ergometric load was increased by 10 W every minute, from zero W to 200 W. The TI/Ttot, ratio increased with V in the range 15 to 60 lmin‐1, indicating that with increasing V˙ the rate of increase of VT/TI decreased whereas that of VT/TE increased. Possible mechanisms responsible for the difference in behaviour of VT/TI and VT/TE are discussed. The VT‐TI and VT‐TE relationships both displayed three ranges with breakpoints at tidal volumes of about 1.4 and 2.4 1. The relations of TI and TE to endinspiratory volume were approximately linear over the entire VT range studied, whereas the relations of TI and TE to end‐expiratory volume showed three ranges with different characteristics. We conclude that the termination of inspiration during cycle exercise is dependent on volume‐related afferent feedback from the lungs and/or chest walls, not only in the high but also in the low volume range.
Effects of prostanoids on isolated feline cerebral arteries
Authors: USKI TORE K. , ANDERSSON KARL‐ERIK
Published: December 2008

The effects of various prostanoids on isolated feline basilar arteries (BA) were studied. Contractions were induced with the following order of potency: U 46619 ≅ U44069 > PGB2 > PGF2a≅ PGA, ≅ PGB, ≥ PGA, ≅ PGE2= PGD2 > PGF1a≅ TXB2≅ PGE1≅ PGD1. Distinct bimodal responses with a relaxation at low concentrations followed by a contraction at high concentrations, were induced by PGA1, PGA2, PGD, and PGE2. None of the tested prostanoids relaxed K+‐contracted arteries, and a sizable relaxant effect in PGF2a‐contracted arteries could be induced only by PGE1. As judged by the relative order of potency, PG‐induced contractions of the feline BA seem to be mediated by a thromboxane sensitive receptor. PGF2a‐induced contractions apparently do not involve the release of noradrenaline from perivascular nerves since phentolamine failed to affect contractions induced by this agent.
Vibrotactile thresholds in mechanoreceptive afferents innervating the foot pad of the cat: The importance of stimulus frequency and duration
Authors: HÄMÄLÄINEN H. , PERTOVAARA A.
Published: December 2008

Vibrotactile thresholds were determined for non‐Pacinian (SA and RA) and Pacinian (PC) mechanoreceptive units innervating the foot pad of the cat with vibratory stimuli of varying frequency (20, 80, and 240 Hz) and duration (100, 400, and 800 ms). Both the absolute (1 impulse/stimulus train) and the tuning (1 impulse/cycle) thresholds of SA and RA units were elevated and those of PC units were decreased as a function of increasing vibration frequency. PC units had the lowest thresholds at 80 and at 240 Hz whereas RA units had the lowest thresholds at 20 Hz. Larger atonal intervals (the range between the absolute and the tuning thresholds) were obtained for all unit types with increasing vibration frequency and PC units had the smallest atonal intervals at all frequencies. The absolute thresholds of all unit types were independent of stimulus duration. The tuning thresholds of SA and RA units were elevated with increasing stimulus duration whereas the tuning thresholds of PC units were independent of stimulus duration. Consequently, larger atonal intervals were obtained for RA and SA but not for PC units with increasing stimulus duration. The results indicate that there are both differences (effect of frequency) and similarities (effect of stimulus duration and the width of atonal intervals) in response characteristics of non‐Pacinian mechanoreceptors innervating the hairy skin and the glabrous foot pad of the cat.
Effects of methoxamine, an alpha‐1 adrenoceptor agonist, and prazosin, an alpha‐1 antagonist, on the stages of the sleep—waking cycle in the cat
Authors: HILAKIVI ILKKA , LEPPÄVUORI ANTERO
Published: December 2008

In these experiments the effects of α1‐adrenoceptor agonism and antagonism were studied on the stages of the sleep‐waking cycle of the cat, in order to determine optimal levels of α1‐adrenergic transmission for these stages. Polygraphic 16‐h recordings showed that prazosin, an α1‐adrenoceptor antagonist, at 1 mg/kg i.p., increased paradoxical sleep (PS) time from 15.3% to 26.4% (p<0.001) of total time, and the number of PS episodes from 30.4 to 43.6 (p<0.001). The effect was prompt, reaching a maximum during the first 4 h with a shortening of PS latency from 40.4 min to 11.0 min (p<0.001). Prazosin at doses of 0.5 and 3.0 though not at 10.0 mg/kg also slightly, but significantly, increased PS. Methoxamine, an α1‐adrenoceptor agonist, at doses of 0.5 and 3.0 mg/kg, increased aroused waking time (low voltage mixed frequency EEG) during the first 4 h from 23.5% to 33.3% (p<0.05) and to 50.3% (p<0.01), and decreased PS. Prazosin potentiated dose‐dependently clonidine‐induced drowsiness (hypersynchronized 4–8 Hz EEG), whereas the decrease in deep slow wave sleep and PS were potentiated only at the largest dose of it. These results indicate that moderate inhibition of cerebral α1‐adrenergic transmission facilitates paradoxical sleep in the cat. Furthermore, they suggest that the level of cerebral α1‐adrenergic transmission is high during aroused waking and low during drowsy waking.
Occurrence, storage and release of neurotensin‐like immunoreactivity from the adrenal gland
Authors: RÖKAEUS ÅKE , FRIED GABRIEL , LUNDBERG JAN M.
Published: December 2008

In the present study we have investigated the presence of radioimmunoassayable neurotensin‐like immunoreactivity (NTLI) in extracts of adrenal glands from hen, guinea‐pig, rat, cat, dog and man. In addition, gel filtration chromatography and studies on the storage site of NTLI, using subcellular fractionation techniques, were performed. Finally, NTLI release in relation to noradrenaline (NA) from cat adrenal glands upon splanchnic nerve activation was studied in vivo. In all species investigated except guinea‐pig and man, the NTLI levels in the adrenal glands were higher than the levels in the heart (control tissue) but lower than in the ileum. Gel filtration of NTLI from cat adrenal glands revealed presence of roughly equal amounts of the whole neurotensin molecule, i.e. NT(1–13), and its main metabolite the N‐terminal octapeptide NT(1–8), while in plasma from the adrenal vein almost exclusively NTd‐13) was revealed after electrical stimulation of the splanchnic nerve. The release of NTLI and NA upon splanchnic stimulation was antagonized by hexamethonium. Subcellular fractionation of cat adrenal glands indicated that NTLI was stored in a large subcellular organelle, co‐migrating with chromaffin granules. We suggest that NT may be a new adrenal gland hormone or transmitter, possibly co‐stored with NA in chromaffin cells. However, at the present stage it cannot be distinguished whether NT exerts its actions locally within the adrenal gland or after release into the systemic circulation.
Reduction of the sucrose‐saline interdiffusion in the sucrose gap technique by controlled compression of the extracellular space in myocardial preparations
Authors: CLEEMANN L. , SUENSON M.
Published: December 2008

The time course and the extent of the sucrose‐saline interdiffusion in the sucrose gap technique was investigated experimentally. 14C‐sucrose diffusion and voltage clamp experiments were performed with designs of the sucrose apparatus allowing accurate control of the size of the holes in the rubber partitions defining the sucrose gap. Experiments with frog ventricular strips demonstrated that compression of the extracellular space to around 15% of its undisturbed value was possible without disturbance of the intracellular conduction pathway. The procedure reduced the sucrose‐saline diffusion significantly and proved indispensible for obtaining reliable voltage‐current relations in voltage clamp experiments.
Further evidence for a glucose‐activated secretory mechanism in the jejunum of the cat
Authors: SJÖVALL HENRIK , JODAL MATS , LUNDGREN OVE
Published: December 2008

The present study was undertaken to further test the hypothesis of a glucose‐induced secretory mechanism in the jejunum of the cat (Sjövall et al. 1983b). The experimental design was based on the sodium dependence of active glucose uptake from the intestinal lumen. The rate of glucose uptake from a sodium‐free and a sodium‐containing perfusate was compared and we also investigated the effect of splanchnic nerve stimulation (SNS) on glucose absorption. The results revealed no difference in “resting” glucose uptake between the two groups. Glucose uptake from the sodium‐free solution decreased on SNS whereas no such effect was seen in the sodium‐containing segments. These findings can be explained by an SNS evoked inhibition of the glucose induced secretion of sodium from the crypts, which will be rate limiting for glucose uptake when no sodium is present in the perfusate. The findings are thus consistent with the concept of a glucose activated sodium secretion. Data are also presented which indicate that this secretory response is mediated by the enteric nervous system.
Differential effects of mecamylamine on the nicotine induced changes in amine levels and turnover in hypothalamic dopamine and noradrenaline nerve terminal systems and in the secretion of adenohypophyseal hormones in the castrated female rat. Evidence for involvement of cholinergic nicotine‐like receptors
Authors: ANDERSSON KURT , FUXEz KJELL , ENEROTH PETER , AGNATI LUIGI F.
Published: December 2008

The effects of mecamylamine on the nicotine induced changes in hypothalamic catecholamine (CA) levels and turnover in female rats ovariectomized for one month have been evaluated using a quantitative microfluorimetric approach to measure CA levels in sections of brains treated according to the Falck‐Hillarp procedure for the cellular demonstration of CA. In the same group of animals the serum prolactin, LH, FSH, TSH, GH and corticosterone levels were measured using radioimmunoassay procedures. The nicotine treatment induced a significant depletion of amine stores and an increase of amine turnover in dopamine (DA) and noradrenaline (NA) nerve terminals of the median eminence and of the peri‐and paraventricular and dorsomedial NA systems of the hypothalamus using the tyrosine hydroxylase (TH) inhibition model. Mecamylamine (2 × 1 mg/kg) partly counteracted the nicotine induced reduction of amine stores in peri‐(anterior part) and paraventricular NA nerve terminal systems as well as the nicotine induced increase of NA turnover in these systems, but not the action of nicotine on the CA systems of the median eminence. Nicotine (4 × 2 mg/kg) significantly and markedly reduced prolactin, LH, TSH, and GH secretion increased corticosterone secretin but did not influence FSH secretion. These effects were partly counteracted by mecamylamine (2 × 1 mg/kg) in the case of prolactin, LH and TSH secretion but not in the case of GH and corticosterone secretion. Taken together the results show that mecamylamine treatment (2 × 1 mg/kg) differentially counteract nicotine induced changes of amine levels and turnover in peri‐(anterior part) and paraventricular NA nerve terminal systems indicating that the cholinergic nicotine‐like receptors located in peri‐(anterior part) and paraventricular areas may be more susceptible to the blocking activity of mecamylamine than those located in the median eminence area. Furthermore, the inhibitory effects of nicotine on prolactin, LH and TSH secretion are differentially counteracted by mecamylamine. In conclusion, other inhibitory systems than the tuberoinfundibular DA neurons in the MPZ and LPZ must also be involved in mediating the inhibitory effects of nicotine on prolactin, LH and TSH secretion and different types of cholinergic nicotine‐like receptors may exist.
Enzyme levels in pools of microdissected human muscle fibres of identified type: Adaptive response to exercise
Authors: ESSÉN‐GUSTAVSSON BIRGITTA , HENRIKSSON JAN
Published: December 2008

Enzyme activities were determined in pools of type I (slow twitch) and IIA and II B (fast twitch) fibres of the thigh muscle from individuals engaged to a high degree in physical training of an endurance character and from non‐endurance‐trained controls. The endurance‐trained (ET) group had significantly higher activity levels of the mitochondrial enzymes citrate synthase, malate dehydrogenase, and 3‐OH‐acylCoA dehydrogenase both in type I (2.1×, 1.7×, 1.4×) and in type IIA (2.3×, 1.8×, 1.4×) and IIB fibres (2.0×, 1.5 ×, 1.5×) than the non‐endurance‐trained (NET) group. Of the glycolytic enzymes, phosphofructokinase (PFK) in type I fibres was significantly higher (I.8×) in the ET than in the NET group whereas glyceraldehydephosphate dehydrogenase (GAPDH) in type I fibres was similar in the two groups. In type II fibres both PFK and GAPDH levels tended to be higher in the ET group. Lactate dehydrogenase (LDH) of both fibre types were not different in the two groups. Type 1 fibres differed significantly from type II fibres for all the six enzymes measured in both groups. However, no significant difference between fibres of types IIA and IIB was found. The results indicate that fibres of types I, IIA and IIB in human skeletal muscle all possess great adaptability with regard to their oxidative capacity. Furthermore, the data suggest that extensive endurance training may enhance the glycolytic capacity in both type I and type II fibres although the glycolytic capacity of the muscle as a whole generally is low in endurance trained subjects owing to a predominance of type I fibres. It is concluded that further studies are needed to determine whether there is a metabolic distinction between fibres of types IIA and IIB.
Calcium‐dependent enhancement by carbachol of the VIP‐induced cyclic AMP accumulation in cat submandibular gland
Authors: ENYEDI PETER , FREDHOLM BERTIL B.
Published: December 2008

The interaction of two coexisting transmitters in the cat submandibular gland has been elucidated by studying effects of VIP and carbachol on cyclic AMP accumulation in isolated acini from the gland. Carbachol was found to potentiate the cyclic AMP increase induced by VIP by an atropine sensitive mechanism. The effect of carbachol on cyclic AMP accumulation was abolished by including EGTA in the incubation medium as was the carbachol mediated potentiation of VIP responses. The calmodulin inhibitor trifluoperazine had a similar, but less marked effect. The effect of carbachol was mimicked by phenylephrine (30 μM) and by the calcium inophore A 23187 (3 μM), and also by ethanol in a concentration reported to enhance membrane fluidity. The phospholipase A2inhibitor, mepacrine, tended to decrease carbachol actions.

Our results show that the poteniation of VIP responses in feline submandibular gland is calcium‐dependent. The mechanism could involve a calcium‐calmodulin‐induced stimulation of adenylate cyclase or calcium‐induced change in membrane phospholipid metabolism.
Adenine nucleotide levels and adenosine metabolism in cultured calvarial bone
Authors: FREDHOLM BERTIL B. , LERNER ULF
Published: December 2008

Adenine nucleotide levels were measured in extracts of murine calvaria after different periods of culture with or without parathyroid hormone (PTH; 10‐8 M) or PGE2 (10‐7 M). In control calvaria the energy charge, (ATP+1/2 ADP)/(ATP+ADP+AMP), remained at close to 0.7 over a 24 hour culture period. However, bones cultured with PTH or PGE2 showed a transient fall in the energy charge down to 0.5. This was not associated with a fall in total adenine nucleotides. The rate of adenosine metabolism in cultured bone in vitro was studied by determining the contents of adenosine, inosine, 2‐deoxyadenosine, 2‐ deoxyinosine and hypoxanthine in the culture medium. There was a continuous increase in adenosine, inosine and hypoxanthine as well as a disappearance of medium 2‐deoxyadenosine that was accounted for by appearance of 2‐deoxyinosine. The deaminating activity could only partly be accounted for by activity in the medium and thus probably mainly resides in the bone cells. PTH (10‐8 M) did not alter the rate of disappearance of 2‐ deoxyadenosine or adenosine deaminase activity determined in bone extracts. The results demonstrate that two substances that increase calcium mobilization from bone alter ATP utilization and/or synthesis without significantly influencing adenosine production or metabolism.
Role of airway resistance in the control of ventilation during exercise
Authors: HESSER C. M. , LIND F.
Published: December 2008

To analyze the interdependence of respiratory drive, ventilation and airway resistance during exercise, mouth occlusion pressure (P0.1), minute ventilation (V) and mean inspiratory flow (VT/TI) were studied in eight normal subjects performing cycle‐ergometer exercise at loads ranging from 0 W to 200 W under two different ambient conditions: 1) during oxygen breathing at 1.3 ATA, and 2) during air breathing at 6 ATA (Po2= 1–3 ATA). Comparison of measurements at 6 ATA with those at 1.3 ATA indicated that a 4.2‐fold increase in respired gas density (D) had little or no influence on the V̇ and VT/TI responses whereas P0.1 at any given VT/TI was increased by a factor of 1.9. In both conditions, P0.1 increased at a faster rate than VT/TI as the work load increased. At loads higher than 40 W, the relationship between P0.1, D and VT/TI was found to approximate the equation P0.1=K·D0.5(VT/TI)1,4 where K is a constant that varies among subjects. The results indicate that the ratio P0.1/(VT/TI), an estimate of respiratory impedance, increased with both D and VT/TI. Evidence is presented that the respiratory drive was reflexly enhanced in response to loading as airway resistance increased with D and/or VT/TI. We conclude that neural mechanisms compensating for internal flow‐resistive loading play an important role in the control of ventilation during exercise, both at normal and at raised air pressures.
Spontaneous variations in arterial blood pressure, heart rate and sympathetic nerve activity in conscious normotensive and spontaneously hypertensive rats
Authors: RICKSTEN S.‐E. , LUNDIN STEFAN , THOREN PETER
Published: December 2008

In the present study we have recorded spontaneous variations in mean arterial blood pressure (MAP), heart rate (HR) and mean rectified splanchnic nerve activity (SNA) in conscious undisturbed normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The variability in blood pressure was not significantly different but HR variability tended to be lower in SHR. The variability in SNA expressed as % change from mean value was not significantly different between SHR and WKY. By computer techniques the correlation between HR, MAP and SNA could be calculated during spontaneous variations of these parameters. The slope of the regression line correlating HR and SNA was significantly steeper in SHR than in WKY (0.73, 0.47 resp.). Thus a certain change in HR was associated by a greater change in SNA in SHR compared with WKY. Spontaneous changes in SNA could be divided in principally two different patterns. One typical pattern was a rise in SNA in parallel with a drop in MAP. This pattern was most likely triggered by the arterial baroreceptors and was called a “baroreceptor‐pattern”. Marked spontaneous excitations in SNA and HR was also observed during natural behaviours such as eating, drinking and explorative behaviour, a so called “centrally mediated pattern”.
Circulatory depression following low frequency stimulation of the sciatic nerve in anesthetized rats
Authors: SHYU B. C. , ANDERSSON S. A. , THORÉN P.
Published: December 2008

Earlier‐experiments have shown that afferent‐electrical‐stimulation‐of‐the sciatic nerve for 30 min induces a long‐lasting post‐stimulatory endorphin‐dependent decrease in blood pressure in awake spontaneously hypertensive rats (SHR). In the present study we have examined whether this depressor response can be observed also in anesthetized SHR. The sciatic nerve was stimulated for 30 min with low‐frequent (3 Hz) trains of impulses and the changes in blood pressure, heart rate and renal nerve activity were observed during the stimulation and in the post‐stimulatory period. Animals anesthetized with Nembutal, Althesin and N2O did not show any post‐stimulatory depression. In contrast, during chloralose anesthesia combined with muscle paralysis with Flaxedil, sciatic nerve stimulation induced a long‐lasting post‐stimulatory decrease in blood pressure due to central inhibition of sympathetic activity. The decrease in blood pressure could be prevented by naloxone and was therefore likely to be mediated via activation of central endorphin systems.
Accumulation and inactivation of adenosine by fat cells from hypothyroid rats
Authors: FREDHOLM BERTIL B. , VERNET LOUISE
Published: December 2008

It has been suggested that the deficient lipolytic response to catecholamines in hypothyroidism may be due to an increased sensitivity to adenosine and/or increased adenosine levels in this condition. We confirmed that the addition of adenosine deaminase enhanced the lipolytic response of hypothyroid fat cells, but the stimulation was at least as large in euthyroid cells. Adenosine analogs were more potent as antagonists of NA‐induced lipolysis in hypothyroid than in euthyroid fat cells, but the difference could be explained by a decreased response to NA. Suspensions of hypothyroid cells accumulated more purine nucleosides (115±20) than did euthyroid cells (48±8 pmol/30 min/105 cells; p<0.01). This difference could not be explained by a lower rate of adenosine elimination, which occurred by three different pathways: uptake followed by phosphorylation, uptake followed by deamination and deamination by the serum albumin preparation. Under certain circumstances the latter pathway is of overwhelming importance. Fat cells from mature rats (460–480 g) behaved similarly as cells from young control rats. Thus, the changes induced by hypothyroidism was not due to a developmental change. The results are discussed in relation to earlier findings on the alterations in catecholamine responsiveness in hypothyroidism. It is concluded that an increased influence of adenosine could possibly explain some aspects of altered catecholamine responsiveness. If it does the mechanism is likely to involve an enhanced amount of adenosine rather than an increased sensitivity to adenosine.
Blood flow distribution, villous tissue osmolality and fluid and electrolyte transport in the cat small intestine during regional hypotension
Authors: REDFORS S. , HALLBÄCK D.‐A. , HAGLUND U. , JODAL M. , LUNDGREN O.
Published: December 2008

The hemodynamic reactions of the parallel coupled vascular circuits in the cat small intestine were studied before, during and after a two‐hour period of intestinal hypotension induced by lowering the intestinal arterial inflow pressure by partially occluding the superior mesenteric artery during a continuous stimulation of the postganglionic nerves to the small intestine. Furthermore, fluid and electrolyte transport and villous tissue osmolality were measured. A histological examination of biopsies taken during and after the hypotensive period was also carried out. The animals were divided into two groups (undamaged and damaged) according to the histological appearance of the intestinal mucosa. The hemodynamic reactions were investigated with a method that made it possible to study total intestinal, absorptive site (“villous”), nonabsorptive site (“crypt”) and muscle layer blood flow. Total intestinal blood flow was lower in the damaged group than in the undamaged group during the arterial hypotension. However, absorptive site blood flow was similar in the two groups. Consequently, a significantly larger fraction of blood flow was distributed to the “villi” in the damaged group. Morover, absorptive site red blood cell flow was only slightly reduced despite the development of mucosal ulcerations. These findings are discussed in relation to the pathophysiology of the mucosal lesions. Net fluid, net sodium and net chloride absorption was unchanged in the undamaged group whereas in the damaged group a marked decrease was observed after lowering the perfusion pressure. The decrease in net sodium absorption was due to a decrease in the lumen to tissue transport of sodium. Thus, the capacity of the small intestine to absorb fluid and electrolytes is unchanged even during a marked arterial hypotension with a pronounced decrease of intestinal blood flow as long as no mucosal damage has developed.
The effect of blood sampling on plasma levels of LH and FSH in male rats
Authors: LAAKSO MAIJA‐LIISA , JOHANSSON GUNNAR , PORKKA‐HEISKANEN TARJA , PEDER MIKAEL
Published: December 2008

Plasma levels of LH and FSH in male rats were compared in blood samples collected by decapitation or through permanently implanted aortic cannulae. The hormone levels were higher in the samples taken by decapitation. After cannulation, the gonadotropin levels remained unchanged when sampling occurred only once a day and each rat was bled 1–3 times over a period of 7 days (sample volume 2.3 ml). The hematocrits of these rats decreased from 42% to 34% after two samplings. In another experiment the LH and FSH levels increased when seven samples had been taken during 24 h. In this experiment the blood cells were reinfused into the circulation, and as a result after 5 samples the hematocrit decreased only from 45% to 40%. A drop in food consumption was observed after cannulation. It is suggested that the increase in gonadotropin levels may be due to the acute stress caused by handling during and before decapitation or decrease in gonadotropin levels may be due to the chronic stress caused by the implanted cannula. The frequent bleedings and cell infusions into the cannulated rats may stimulate the secretion of gonadotropins, opposing the effect of chronic stress.
Renal venous and urinary PGE2output during intrarenal arachidonic acid infusion in dogs
Authors: SEJERSTED OLE M. , VIKSE ARILD , EIDE IVAR , KIIL FREDRIK
Published: December 2008

Inferences about total renal (venous and urinary) PGE2output from determinations of urinary excretion rates (UPGE2V) cannot be made unless the distribution of PGE2between renal venous plasma and urine is known. Therefore, in the present study on intact kidneys of anesthetized dogs both urinary excretion of PGE2and the renal venous output (the product of plasma flow and venous concentration of PGE2) was determined during low and high rates of renal PGE2synthesis. PGE2was measured in urine and arterial and renal venous plasma by radioimmunoassay during the following conditions: (1) Hydropenia. In the control condition UPGE2V averaged 0.041±0.012 pmol/g·min and varied between 4 and 70% of the total PGE2output. With infusion of arachidonic acid (AA, 160 μg/kg·min) into the renal artery total PGE2output increased from 0.18±0.03 to 3.23±0.51 pmol/g·min, whereas arterial concentrations of PGE2were unchanged. The urinary fraction still varied between 6 and 46% of total renal PGE2output. (2) High urine flows caused by mannitol, saline or saline and ethacrynic acid (ECA) infusion. These procedures did not stimulate total renal PGE2output and the urinary fraction varied between 4 and 49%. ECA combined with saline infusion increased the urinary fraction significantly to 34.7±4.0%. AA increased the total PGE2output as during hydropenia, but the urinary fraction fell to 13% in 13 dogs and was unchanged at about 8% in six dogs. On average the urinary fraction of total PGE2output was significantly lower than in hydropenia. Thus, the urinary fraction of total renal PGE2output is not constant, and urinary excretion of PGE2does not give reliable information about renal synthetic rates of prostaglandins.
VIP inhibition of vascular smooth muscle: complementary to β2‐adrenoceptor mediated relaxation in the isolated rat portal vein
Authors: BRÅTVEIT M. , HELLE K. B.
Published: December 2008

Exogenous VIP caused a concentration dependent inhibition of the spontaneous mechanical activity in the isolated rat mesenteric‐portal vein preparation via a mechanism which was completely independent of the propranolol‐blocked β‐adrenoceptor, of high K+ in the medium and of exogenous bovine pancreatic polypeptide, neurotensin and opioids. The potency of VIP ((pD2=7.52±0.18, n=6) was about 30 times higher than that of isoprenaline in the atropine and phentolamine‐blocked preparation. The isoprenaline inhibition was mediated via a β2‐type of adrenoceptor with low apparent affinity for noradrenaline (intrinsic activity (a) = 0.27±0.01, n=8). Opposite effects of exogenous VIP and noradrenaline were on the other hand observed in the atropinized and β‐blocked preparation. These results suggest that in the rat portal vein neuronal VIP and circulating adrenaline may be complementary in their antagonism of the α‐adrenoceptor mediated increase in contractility.
Mechanisms for reflexive hypertension induced by local application of capsaicin and nicotine to the nasal mucosa
Authors: LUNDBLAD LARS , HUA XIAO‐YING , LUNDBERG JAN M.
Published: December 2008

The cardiovascular effects of locally applied nicotine and capsaicin to the nasal mucosa were studied in anaesthetized guinea‐pigs. Local application of capsaicin (0.3–30 μM) or nicotine (0.3–30 mM) induced dose‐dependent increases in arterial blood pressure, mainly due to an increase in peripheral vascular resistance. The capsaicin and nicotine responses were abolished after local anaesthesia and markedly reduced (to about 20% of control) by combined pretreatment with phentolamine and propranolol, suggesting reflexogenic sympathetic activation. Systemic capsaicin pretreatment abolished the hypertensive effect of capsaicin (30 μM) and reduced the response to nicotine application to about 25% of control (p<0.001). Local capsaicin pretreatment of the nasal mucosa one week earlier also significantly reduced the capsaicin response (p<0.05), while the nicotine‐induced increase in blood pressure was not significantly changed. The present findings suggest the presence of two afferent mechanisms in the nasal mucosa which induce hypertension upon chemical irritation. The capsaicin response is dependent upon capsaicin‐sensitive afferents. The nicotine response involves mainly capsaicin‐sensitive neurons and, in addition, a minor component which is resistant to capsaicin pretreatment. Thus, the hypertensive effect of nicotine applied locally to the nasal mucosa seems to be mainly mediated via sensory mechanisms other than the sneezing response which is not dependent on capsaicin sensitive nerves.
Efferent sympathetic nervous control of rectal motility in the cat
Authors: HEDLUND H. , FASTH S. , HULTÉN L.
Published: December 2008

The sympathetic nervous control of rectal motility was studied in anasthetized cats. Division of the sympathetic nerves, i. e. the hypogastric nerves and the lumbar colonic nerves and alpha‐adrenergic blockade reduced rectal tone indicating that these nerves are tonically active. Efferent electrical stimulation of the nerves at high intensities caused an immediate and sustained contraction which was inhibited after phentolamine but unaffected by hexamethonium suggesting a direct alpha‐adrenergic effect on the rectal smooth muscle. However when prevailing rectal tone was high beta‐adrenergic inhibitory responses unaffected by hexamethonium were observed. In addition the hypogastric nerves seem to convey cholinergic excitatory fibres to the rectum. The results imply that the sympathetic nerves are integrated in the nervous regulation of rectal motility in a fashion similar to the nervous control of the internal anal sphincter.
Effects of neuropeptide Y (NPY) on mechanical activity and neurotransmission in the heart, vas deferens and urinary bladder of the guinea‐pig
Authors: LUNDBERG JAN M. , HUA XIAO‐YING , FRANCO‐CERECEDA ANDERS
Published: December 2008

The effects of preincubation for 10 min with synthetic porcine neuropeptide Y (NPY) on muscle tone and autonomic transmission in the guinea‐pig right atrium, vas deferens, urinary bladder, portal vein and trachea were analysed in vitro. NPY induced a metoprolol‐resistant, long‐lasting, positive inotropic and cronotropic effect per se in the spontaneously beating right atrium. Furthermore, NPY caused a reversible inhibition of both the metoprolol and atropine‐sensitive auricle responses to field stimulation (2 Hz or 4 Hz for 2 s) without affecting the response to exogenous noradrenaline (NA) or acetylcholine (ACh).

NPY did not induce any contraction of the vas deferens, but inhibited both the rapid twitch response and the sustained tonic contraction induced by field stimulation. The NPY‐induced inhibition of the tonic contraction was more long‐lasting than that of the twitch response. The tonic contraction was blocked by phentolamine and the twitch response by α‐, β‐methylene ATP tachyphylaxis. NPY did not inhibit the contractile effects of NA, ATP or α‐, β‐methylene ATP. NPY also induced a reversible reduction of the non‐cholinergic, non‐adrenergic contractile response to field stimulation of the urinary bladder. In the portal vein, NPY (up to 5×10–7M) did not inhibit the spontaneous motility or the phentolamine‐sensitive contractile responses to field stimulation and NA. The atropine‐sensitive contraction of the trachea or the non‐adrenergic, non‐cholinergic relaxation induced by field stimulation were not significantly influenced by NPY in doses up to 5×10–7M. In conclusion, the present data show that in the guinea‐pig, NPY exerts positive chronotropic and inotropic effects on the right atrium of the heart. Furthermore, NPY may have presynaptic effects on adrenergic, cholinergic and non‐adrenergic—noncholinergic neurotransmission.
Nervous control of the release of neurotensin‐like immunoreactivity from the small intestine of the rat
Authors: AL‐SAFFAR AHMAD , THEODORSSON‐NORHEIM ELVAR , ROSELL SUNE
Published: December 2008

Intraduodenal administration of oleic acid increased plasma neurotensin‐like immunoreactivity (p‐NTLI). The integrated responses to saline and oleic acid were 5.7 and 9.7 nM0–180 respectively. The integrated response was not significantly altered by i. v. administration of atropine, guanethidine, mepyramine, cimetidine, methysergide or a substance P antagonist, but it was abolished by hexamethonium and morphine (5.9 and 6.3 nM0–180 respectively). An exogenous supply of bile and pancreatic juice did not alter the integrated response in morphine‐and hexamethonium‐treated rats. Haloperidol significantly increased the p‐NTLI response to oleic acid (13 nM0–180min). The results suggest that the release of neurotensin is influenced by nervous pathways involving nicotinic and opioid receptors. Catecholamines and 5‐HT receptors may exert an inhibitory influence on the release of NTLI.
Functional evidence for sprouting or decentralized parasympathetic neurons in rat urinary bladder
Authors: EKSTRÖM JÖRGEN , MALMBERG LARS
Published: December 2008

The pelvic nerve, carrying parasympathetic nerve fibres, distributes bilaterally in the rat urinary bladder. Preganglionic parasympathetic denervation (decentralization) on one side and postganglionic parasympathetic denervation on the other are followed by an initial decrease in acetylcholine forming capacity and in number of acetylcholinesterase positive nerves in the bladder. However, within a few weeks a marked recovery in acetylcholine synthesis and in number of nerves, based on collateral sprouting, occurs. In this study muscle strips of the rat urinary bladder exposed to the combined surgical procedure was studied. The strips were taken from “denervated” and “decentralized” halves of the bladder. Their contractile responses to methacholine and transmural electrical field stimulation were isometrically recorded in vitro. A supersensitivity to methacholine was found to have developed, of about the same degree, in the two halves 1 week postoperatively. In the denervated halves 4 weeks postoperatively, the supersensitivity was even more marked, whereas in the decentralized halves it tended to be less than after 1 week. The responses of denervated halves to electrical stimulation were reduced 1 week postoperatively. This was also the case for decentralized halves, although the reduction was not large enough to be significant. When examined 4 weeks postoperatively the responses, in particular in denervated halves, were enlarged compared to those 1 week postoperatively. The atropine‐sensitive portion of the responses increased with time. Increases in contractile responses to electrical stimulation accompanied by a tendency to desensitization to methacholine are taken as functional evidence for outgrowth of decentralized parasympathetic neurones in the decentralized halves. The gradual development of sensitization with time may in part explain the increasing responses to electrical stimulation in the denervated halves.
Arteriovenous difference of plasma vasopressin in normal man and effect of posture
Authors: OS INGRID , KJELDSEN SVERRE ERIK , AAKESSON INGVAR , SKJØTØ JOHN , WESTHEIM ARNE , EIDE IVAR , LEREN PAUL
Published: December 2008

In 13 normotensive 50‐year‐old men arterial plasma vasopressin (11.3 ± 2.1 ng/l, mean ± SE) was significantly increased over venous (7.8 ± 1.4 ng/l) in the supine position with an arteriovenous difference of 3.5 ± 1.2 ng/l (p<0.05). After 30 min in the upright position, an average increment of 45% to 11.3 ± 1.8 ng/l was observed for venous vasopressin. Since a similar increase was not found for arterial vasopressin, the arteriovenous difference decreased with 29% to 2.5 ± 2.1 ng/l and was no longer statistically significant. The correlation between supine and standing vasopressin was statistically significant both for arterial (p<0.001) and venous plasma (p<0.05). These data indicate a substantial removal of plasma vasopressin by receptors even in the peripheral vascular beds (forearm) and not only in the liver and the kidneys as previous literature claims. The arteriovenous difference decreases in the upright position, most likely because of reduced plasma vasopressin clearance.
Effects of gastric inhibitory polypeptide on dispersed pancreatic acinar cells from the guinea pig
Authors: SJÖDIN LARS , CONLON THOMAS P.
Published: December 2008

Purified natural porcine gastric inhibitory polypeptide (GIP), in high concentrations, was found to stimulate outflow of 45Ca, increase cellular accumulation of cyclic GMP and cyclic AMP and cause release of amylase from dispered pancreatic acinar cells. Synthetic GIP increased cellular cyclic AMP levels, but did not affect outflux of calcium, cellular levels of cyclic GMP or release of amylase. The discrepancy between results with natural and synthetic preparations of porcine GIP may be explained by a possible contamination of natural GIP with cholecystokinin. Other examined pancreatic secretory stimulating peptides which induce cyclic AMP accumulation in acinar cells, also increase release of amylase. Synthetic GIP increased levels of cyclic AMP without affecting amylase release. This suggests that the correlation between amylase release and total cellular accumulation of cyclic AMP in response to GIP is not close.
Effect of K‐depletion on 3H‐ouabain binding and Na–K‐contents in mammalian skeletal muscle
Authors: KJELDSEN KELD , NØRGAARD AAGE , CLAUSEN TORBEN
Published: December 2008

K‐depletion induced by K‐deficient fodder led to hypokalemia, decreased K‐content and increased Na‐content in skeletal muscle of rats. The heart showed similar, although more modest changes, whereas brain, erythrocytes and liver maintained virtually constant Na–K‐contents. K‐depletion decreased total binding capacity for 3H‐ouabain by up to 76%, an effect which could be demonstrated both in vitro and in vivo. Following 3 weeks of K‐depletion, the apparent KD for 3H‐ouabain binding to rat soleus was 1.3times10‐7 M as compared to 2.4times10‐7 M in controls. Also in mice and guinea pigs, K‐depletion induced a selective loss of K from muscle and decreased 3H‐ouabain binding capacity. K‐depletion induced by diuretics or fluorohydrocortisone gave similar effects. The effects of K‐depletion on 3H‐ouabain binding capacity were confirmed by measurements of 3‐O‐methylfluorescein phosphatase activity, an enzyme activity which is closely correlated to the Na–K–ATPase activity. Following readministration of K, the K‐contents of plasma and muscle reached control levels in 24 hours, but 3H‐ouabain binding capacity was not normalized until after 6 days of K‐repletion. In mammalian skeletal muscle, K‐depletion leads to a marked and reversible reduction in 3H‐ouabain binding capacity, which may be secondary to the selective loss of K or gain of Na.
Cardiopulmonary blood volume during acute blood pressure elevations in dogs
Authors: THORVALDSON JØRGEN , STOKLAND OLAV , MOLAUG MÅLFRID , ILEBEKK ARNFINN
Published: December 2008

During aortic blood flow obstructions and angiotensin infusion blood may be accumulated in the heart and the lungs because of retention or redistribution of blood from compliant regions. We measured the cardiopulmonary blood volume (CPBV) when left ventricular systolic pressure was raised by about 50 mmHg by angiotensin infusion and by balloon inflation in the ascending and descending thoracic aorta, at control inotropy and during isoproterenol infusion, in 6 anesthetized, closed‐chest dogs. CPBV was calculated from determinations of cardiac output (thermodilution) and the interventricular mean transit time of ascorbate (polarographic determination). Angiotensin always increased CPBV, but the rise was greater at high than at control inotropy (16.5±4.4% and 5.1±1.2%). Balloon inflation in the descending thoracic aorta increased CPBV similarly at high and control inotropy (11.1±2.4% and 16.6±4.0%) whereas CPBV was unaltered or fell during inflation in the ascending aorta at both inotropic levels. Right and left ventricular end‐diastolic pressures rose only during angiotensin infusion and balloon inflation in the descending thoracic aorta. By balloon inflation, cardiac output only fell during blood flow obstruction in the ascending aorta. Thus, an increase in CPBV during these interventions is not due to retention but is caused by redistribution of blood towards the heart.
Leg citrate metabolism at rest and during exercise in relation to diet and substrate utilization in man
Authors: JANSSON EVA , KAIJSER LENNART
Published: December 2008

Previously we have demonstrated a lower rate of carbohydrate utilization in skeletal muscle after a fat than after a carbohydrate rich diet both at rest and during exercise. To test the hypothesis of citrate as a regulator of glycolysis (1) arterial‐femoral venous (a‐fv) differences for oxygen, citrate, pyruvate and lactate and (2) muscle citrate and glucose‐6‐phosphate (G‐6‐P) were determined at rest and after 5 and 25 min of submaximal bicycle exercise. Citrate release and muscle citrate concentration were higher after fat than after carbohydrate diet at rest and 5 min exercise, but did not differ between diets at 25 min exercise. Lactate release and muscle lactate concentration were lower after fat diet at 5 and 25 min exercise. Pyruvate release at 5 min exercise was higher after fat diet. The G‐6‐P concentration was higher at rest, insignificantly higher after 5 min exercise and lower at 25 min exercise after the fat diet. The findings support the notion that at rest and 5 min exercise fat diet induced inhibition of glycolysis might be mediated through increased intramuscular citrate acting on phosphofructokinase. In addition, the greater pyruvate release at 5 min exercise after fat diet in spite of a smaller lactate release, indicates a decreased pyruvate dehydrogenase activity and/or NADH to NAD ratio after fat diet. The inhibition of glycolysis at 25 min exercise after fat diet on the other hand does not seem to be citrate mediated.
Neuropeptide Y: Immunocytochemical localization to and effect upon feline pial arteries and veins in vitro and in situ
Authors: EDVINSSON LARS , EMSON PIERS , McCULLOCH JAMES , TATEMOTO KAZUHIKO , UDDMAN ROLF
Published: December 2008

Plexuses of nerve fibres containing neuropeptide Y (NPY)‐like immunoreactivity invest pial arteries belonging to the circle of Willis, pial arterioles, occasionally penetrating arterioles and large veins. A more sparse supply of NPY‐like fibres are observed around pial veins and venules. The NPY‐immunoreactive fibres are located within the adventitia or at the adventitia‐media border. Only occasional fibres are present in cerebral vessels of animals in which the superior cervical ganglion has been removed one week previously. Administration of NPY resulted in strong, concentration‐dependent contractions of isolated feline middle cerebral arteries whereas administration of avian pancreatic polypeptide (APP) elicited weak contractions. In chloraloseanaesthetized cats, perivascular microapplication of NPY in situ resulted in marked concentration‐dependent contractions of cerebral pial arterioles (34.7±6.6%; maximum decrease in calibre with NPY. Perivascular administration of NPY resulted in the constriction of pial veins but the magnitude of the venous calibre reductions was smaller than the response of arterioles at each reductions was smaller than the response of arterioles at each concentration examined. APP did not elicit contraction of pial arterioles or veins during in situ conditions. The pharmacological and immunocytochemical results strongly indicate the existence of a novel perivascular neuronal system containing NPY, which mediates contraction of cerebral blood vessels and NPY is colocalized with NA in sympathetic nerves.
Development of supersensitivity to methacholine in the rat detrusor following either parasympathetic denervation or decentralization
Authors: EKSTRÖM JÖRGEN , MALMBERG LARS
Published: December 2008

The male rat urinary bladder belongs to those few structures where both the post‐ and preganglionic parasympathetic nerves are accessible for severance. In the present study the sensitivity to the parasympathomimetic drug methacholine of muscle strips of either denervated or decentralized bladders was examined in vitro. One week postoperatively denervated and decentralized bladders were sensitized to the same degree, the ED50 values being 4 times less than ED50 of unoperated control bladders. In contrast to the decentralized bladders the supersensitivity in the denervated ones was found to have increased further when tested four weeks postoperatively, the ED50 value being about 20 times less than that of controls. The present findings are in agreement with Cannon's “law of denervation”. The results are discussed in relation to possible mechanisms behind the phenomenon of supersensitivity.