bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell calcium concentration in glomerular afferent and efferent arterioles under the action of noradrenaline and angiotensin II
Authors: KORNFELD M. , GUTIERREZ A. M. , GONZALEZ E. , SALOMONSSON M. , PERSSON A. E. G.
Published: December 2008

The glomerular arterioles in the juxtaglomerular apparatus seem to function as effectors of the tubuloglomerular feedback mechanism. In this mechanism increased delivery of fluid to the distal nephron activates the macula densa cells through transport via an Na‐2C1‐K cotransporter. This activation may lead to vasoconstriction of the afferent arteriole. Furthermore, vasoactive substances seem to affect both afferent and efferent arterioles. There are morphological differences along the afferent arteriole, some parts containing epithelioid cells with renin granules and others regular smooth muscle cells. The aim of the present experiments was to determine whether noradrenaline (10˜6 M) and angiotensin II (10˜6 M) had differential effects on the cell calcium concentration [Ca2+]j and on contraction in isolated perfused afferent and efferent arterioles and in the mesangial region. [Ca2+], was measured with fura‐2, an intensified videocamera and a digital imaging system. From the proximal to the distal part of the arteriole [Ca2+], increased from about 100 to 250 nM. A [Ca2+], increase and a contraction were caused by noradrenaline alone in the proximal part of the afferent arteriole and by angiotensin II alone in the distal part of this arteriole. In the mesangial region there was a high basal [Ca2+], but no response to the vasoactive substances. In the efferent arteriole, application of both noradrenaline and angiotensin II led to an increase in [Ca2+]1 and a contraction. The present experiments indicate that the two vasoactive substances tested act in a similar fashion along the whole length of the efferent arteriole, while in the afferent arteriole their actions are not equally distributed.
Developmental studies on vasoactive intestinal peptide, substance P and calcitonin gene‐related peptide in salivary glands of postnatal rats
Authors: EKSTROM J. , EKMAN R. , HÅKANSON R. , LUTS A. , SUNDLER F.
Published: December 2008

The development of vasoactive intestinal peptide, substance P and calcitonin gene‐related peptide in parotid, submandibular and sublingual glands of the male rat was followed by immunochemistry and immunocytochemistry. The total amounts of these peptides increased in surges during the first 8 weeks of the animal's life; one within 2–4 weeks and the other beginning 1–2 weeks later. Nerve fibres containing these peptides were present at birth showing a pattern of distribution similar to that in adults. During the first 4 weeks the nerve fibres increased in number.
Prolonged bleeding time during nitric oxide inhalation in the rabbit
Authors: HOGMAN M. , FROSTELL C. , ARNBERG H. , SANDHAGEN B. , HEDENSTIERNA G.
Published: December 2008

During a study on the modulatory effect of inhaled nitric oxide (NO) on the airway, we observed an increased bleeding tendency. Therefore, we studied bleeding time and blood rheology in rabbits during inhalation of 3, 30 and 300 parts per million (ppm) NO. The rabbits were intubated during neurolept anaesthesia and were ventilated mechanically. The bleeding time was significantly increased after 15 min of inhalation of 30 ppm NO, from 51 + 5 to 72 + 7 s (mean + SEM, P < 0.001, n= 7). However, there were no changes in haematocrit, whole blood or plasma viscosity, erythrocyte aggregation tendency, or erythrocyte deformability. Inhalation of 3 ppm NO increased bleeding time from 46+11 to 59 + 8 s (n.s., n= 4) and 300 ppm NO from 48 + 12 to 78 + 17s(P<0.05, n= 4).

In another group of rabbits mean arterial pressure (MAP) was monitored using NO inhalation. A non‐significant decrease was seen with 3 ppm and 30 ppm NO, from 63 + 2 to 59 + 3 mmHg (n= 6) and from 65 + 2 to 61 + 1 mmHg (n= 6) respectively. Inhalation with 300 ppm NO decreased MAP from 62 + 3 to 55 + 2 mmHg (P < 0.05, n= 6). We conclude from these data that inhalation of NO, 30 ppm or more exerts systemic effects.
Lipid peroxidation and antioxidative vitamins under extreme endurance stress*
Authors: ROKITZKI L. , LOGEMANN E. , SAGREDOS A. N. , MURPHY M. , WETZEL‐ROTH W. , KEUL J.
Published: December 2008

The aim of this study was to examine whether extreme endurance stress of trained athletes can influence lipid peroxidation and muscle enzymes. A randomized and placebo‐controlled study was carried out on 24 trained long‐distance runners who were substituted with α‐tocopherol (400 I.U. d‐1) and ascorbic acid (200 mg d‐1) during 4.5 weeks prior to a marathon race. The serum concentrations of retinol, ascorbic acid, β‐carotene, α‐tocopherol, malondialdehyde (TBARS) and uric acid as well as gluthation peroxidase (GSH Px) and catalase were measured 4.5 weeks before (A), immediately before (B), immediately after (C) and 24 h after (D) the course. After competition (C) TBARS serum concentrations of the athletes (n= 22) decreased in both groups (P < 0.0001). The ascorbic acid serum concentration increased significantly in the supplemented group from (A) to (B) (P < 0.01), from (B) to (C) (P < 0.001) and in the placebo group a significant increase from (B) to (C) (P < 0.01) was observed. The α‐tocopherol serum concentration increased significantly in the supplemented group from (A) to (B) (P < 0.001) and from (B) to (C) (P < 0.05). The enzymes glutathione peroxidase (GSH Px) and catalase measured in erythrocytes as well as the serum selenium levels did not show significant differences at any time. A significant increase of CK concentration was observed from (C) to (D) in the supplemented group (P < 0.01) and in the placebo group (P < 0.001). The increase of CK serum concentration is remarkably lower in the supplemented group compared with the placebo group (P < 0.01). It is concluded that endurance training coupled with antioxidant vitamin supplementation reduces blood CK increase under exercise stress.
Effect of anaesthetizing the region of the paraventricular hypothalamic nuclei on energy metabolism during exercise in the rat
Authors: VAN DIJK G. , VISSING J. , STEFFENS A. B. , GALBO H.
Published: December 2008

The ventromedial and posterior hypothalamic nuclei are known to influence glucoregulation during exercise. The extensive projections of the paraventricular hypothalamic nucleus (PVN) to the sympathetic nervous system suggest that the PVN also may be involved in glucoregulation during exercise. The region of the PVN was anaesthetized with bupivacaine before running (26 m min‐1) or continued rest, via previously implanted bilateral brain cannulas aimed at the dorsal aspect of the PVN. Control rats were treated identically to PVN‐anaesthetized rats, but were not infused. Blood, for determination of plasma concentrations of metabolites and hormones, was drawn from a tail artery, and 3H‐glucose was infused in a tail vein for glucose turnover determinations. At rest, no significant changes in plasma concentrations of metabolites or hormones were induced by anaesthesia of the region of the PVN. During exercise, glucose production and utilization and plasma concentrations of glucose, lactate, glycerol, noradrenaline, adrenaline, corticosterone, and glucagon increased (P < 0.02) and plasma insulin decreased (P < 0.02) in all rats. However, initially in exercise, adrenaline (4.3 ±0.8 vs. 7.9 ± 1.0 nmol 1‐1 in controls, P < 0.05, t= 6 min) and later corticosterone levels (1.37 ± 0.06 vs. 1.69 ± 0.10 nmol 1‐1 in controls, P < 0.05, t = 20 min) were attenuated by PVN anaesthesia. Initially during exercise, glucose utilization was higher and plasma glucose lower in PVN‐anaesthetized rats compared to controls (16.6 ± 0.8 vs. 12.7 ± 0.6 μmol min‐1 100 g‐1 and 7.1 ± 0.2 vs. 8.1 ± 0.2 mmol 1‐1, respectively. P < 0.05, t= 6 min) and exercise‐induced liver glycogen breakdown was only significant in the controls. In conclusion, the region of the PVN does not influence glucoregulation at rest, but affects glucoregulation during exercise, by stimulating adrenaline and corticosterone secretion during exercise.
A comparison between endogenous and exogenous lithium clearance in the anaesthetized rat
Authors: LEYSSAC P. P. , CHRISTENSEN P.
Published: December 2008

The present study tests whether the endogenous renal lithium clearance (CLi) may be used as an alternative to the conventional method in order to avoid the adverse effects of exogenous lithium on renal function. Endogenous CLi) was measured by nameless atomic absorption spectrometry (AAS) in halothane anaesthetized, laparotomized rats and compared with values obtained after subsequent intravenous (i.v.) administration of LiCl. Endogenous plasma lithium concentration (PLi) was 0.30 ± 0.06 μmol 1‐1. When measured by both conventional flame emission AAS and flameless AAS on the same samples, values for PLi did not differ significantly. Endogenous CLi/GFR was 0.195 ± 0.01 (means± SEM). Amiloride caused no significant change in either the endogenous CLi or 51Cr‐EDTA clearance, a measure of glomerular filtration rate (GFR), but it caused a significant increase in CNa. Administration of exogenous Li+ had no significant effect on CLi (230 ±33 vs. 234 ±35 μ min‐1 gKW‐1); both urine flow and CNa increased significantly (P < 0.01) (5.4±0.4 vs. 9.6± 1.3, and 2.4±0.5 vs. 10.7 ± 2.4/d min‐1 gKW‐1, respectively). GFR and calculated proximal tubular reabsorption rate (APR) both decreased by ˜ 100 μ min‐1 gKW‐1 (both P≪ 0.025), suggesting a moderate inhibition of APR after the acute elevation of plasma Li+ concentration. It is concluded that the endogenous CLi may be used as an alternative to the conventional method.
Temporal heterogeneity of the blood flow velocity at the middle cerebral artery in the normal human characterized by fractal analysis
Authors: ROSSITTI S. , STEPHENSEN H.
Published: December 2008

The objective of this study is to characterize the temporal fluctuation of the axial blood flow velocity (BFV) at the middle cerebral artery (MCA). Biological observables such as BFV present complex oscillations. The irregularity of physiological systems may be assessed by fractal analysis by computing the fractal dimension (Dγ) and the corresponding temporal correlation (rγ). The BFV at the MCA was registered with transcranial Doppler ultrasonography (TCD) in four adult volunteers. As fractal processes are assumed to have no absolute time scale, two time scales were compared. The digitized signal was averaged respectively at 1‐s intervals and for each heart beat. Dγ and rγ were determined using relative dispersion analysis. The results were Dγ= 1.24 ± 0.09 and rγ= 0.45 ± 0.19 (mean ± SD) for the 1‐s based time scale and Dr= 1.17 ± 0.09 and rγ= 0.57 ± 0.20 for the heart‐beat scale. We conclude that the temporal heterogeneity of the BFV at the MCA in the normal human has fractal properties. Fractal analysis of TCD data may become useful in clinical diagnosis because loss of complexity in physiological systems has been linked to senescence or disease conditions. Wide variations of the so called normal values of BFV measured by TCD have been reported. The physiological BFV fluctuations may explain, in part, the variability of values recorded during routine TCD diagnostic examinations. Our observations may also be of value for understanding the interaction of the vascular endothelium and the blood flow stream (shear stress).
Haemodynamic changes induced by short‐ and long‐term sodium chloride or sodium bicarbonate intake in deoxycorticosterone‐treated rats
Authors: ZICHA J. , KUNEŠ J.
Published: December 2008

The contribution of chloride to the haemodynamic changes of salt‐dependent deoxycorticosterone (DOC) hypertension was studied in young Wistar rats subjected to dietary loading with sodium chloride (NaCl) or sodium bicarbonate (NaHCO3). Mean arterial pressure (MAP), cardiac output, systemic resistance (TPR) and arterial rigidity (estimated from pulse pressure/stroke volume ratio, PP/SV) were determined in conscious chronically cannulated rats. DOC‐induced increase of MAP and TPR appeared earlier in NaCl‐loaded than in NaHCO3‐loaded rats. After 4–6 weeks of hypertensive treatment MAP, TPR and PP/SV ratio were higher in DOC‐treated rats fed NaCl diet than in those fed NaHCO3 diet. In contrast, after a long‐term hypertensive regimen (lasting for 7–9 weeks) there was no significant difference in either MAP or TPR between rats loaded with NaCl or NaHCO3. On the other hand, DOC hypertension induced by a long‐term feeding of NaHCO3 diet was not associated with an increase of arterial rigidity which was characteristic for DOC‐NaCl hypertensive rats. Thus, a sufficiently long selective dietary sodium loading is capable to increase the systemic resistance but not to alter the arterial rigidity. This was also confirmed by a comparison of blood pressure‐matched DOC hypertensive rats fed NaCl or NaHCO3 diets. These animals did not differ in the degree of systemic resistance elevation but the arterial rigidity was increased only in NaCl‐loaded rats.
Intracerebroventricularly administered corticotropin‐releasing factor releases somatostatin through a cholinergic, vagal pathway in freely fed rats
Authors: SMEDH U. , UVNÄS‐MOBERG K.
Published: December 2008

The aim of this study was to investigate whether corticotropin‐releasing factor influences the plasma levels of somatostatin, gastrin or cholecystokinin when administered intracerebroventricularly to rats, and if such an effect could be vagally mediated, and dependent on the animals feeding states. Anaesthetized, freely fed rats were given 5 μl intracerebroventricular injections of corticotropin‐releasing factor in four doses; 10 pmol‐1.28 nmol. Immediately following death, trunk blood was collected for subsequent peptide analysis with radioimmunoassay (RIA). The three higher doses of corticotropin‐releasing factor elevated the plasma levels of somatostatin (P < 0.01) after 20 min but left the plasma levels of gastrin and cholecystokinin unchanged. Intraperitoneal injections of 60 and 320 pmol of corticotropin‐releasing factor did not influence the somatostatin levels. Further, intracerebroventricular injections of 60 pmol of corticotropin‐releasing factor produced a peak increase in somatostatin after 20 min (P < 0.01). After 60 min the somatostatin levels were still increased (P < 0.05). Gastrin and cholecystokinin remained unaltered at these timepoints. Intracerebroventricular administration of 10 nmol of a‐helical corticotropin‐releasing factor 9–41 attenuated the basal levels of somatostatin and blocked the corticotropin‐releasing factor‐induced rise in somatostatin. Bilateral truncal vagotomy, as well as pretreatment with atropine (0.05 mg kg‐1, subcutaneously) abolished the effects of corticotropin‐releasing factor on somatostatin. In animals which were food‐deprived for 24 h, corticotropin‐releasing factor did not influence somatostatin, gastrin or cholecystokinin. Pretreatment with cholecystokinin did not potentiate corticotropin‐releasing factor‐induced somatostatin release in food‐deprived rats. These findings suggest that corticotropin‐releasing factor acting within the central nervous system may regulate gastrointestinal functions partially through a cholinergic, vagally mediated release of somatostatin in freely fed, but not in food‐deprived rats.
Microdialysis of rat skeletal muscle and adipose tissue: dynamics of the interstitial glucose pool
Authors: FUCHI T. , ROSDAHL H. , HICKNER R. C. , UNGERSTEDT U. , HENRIKSSON J.
Published: December 2008

Microdialysis was evaluated as a method for studying glucose metabolism in skeletal muscle. Dialysis probes (0.5 × 10 mm) were perfused at 0.5 or 1.0 μl min‐1. Based upon perfusion with glucose, the muscle interstitial glucose concentration was estimated to be 6.9 ± 0.3 mM (w = 14), which was not significantly different from the blood glucose level. With insulin infusion (1200 mU kg‐1 body wt i.v.), the insulin‐induced change in the glucose concentration of the interstitial space of muscle was of equal magnitude to that of blood and adipose tissue. In spite of this, when the perfusion medium was not supplemented with glucose, the glucose concentration decreased more in skeletal muscle dialysates (to 36.7 ± 4.9% of the initial level) than in blood (to 29.7±5.0%) but less than in adipose tissue (to 17.7 ± 4.9% of the initial level) (P < 0.05). The results indicate that these differences are due to tissue‐specific differences in the dynamic balance between the supply to, and removal from, the interstitial glucose pool. This balance is revealed as a result of the constant glucose drainage by the microdialysis probe. The present results show that, in skeletal muscle, increases in glucose uptake occur with a concomitant increase in tissue blood flow as revealed by the microdialysis ethanol technique, whereas in adipose tissue the glucose uptake increases in the absence of a corresponding increase in blood flow.
Gi‐mediated muscarinic adenylyl cyclase inhibition in timolol‐treated stunned porcine myocardium
Authors: FU M. L. X. , ILEBEKK A. , XU X. , PERGOLA G. , ERIKSSON P. , KIRKEBØEN K. A. , AKSNES G. , HOEBEKE J. , HJALMARSON Å.
Published: December 2008

The Gi‐mediated muscarinic receptor‐adenylyl cyclase system was examined in stunned myocardium induced by either three or five brief ischaemic periods after β‐adrenoceptor blockade by timolol (0.1 mg kg‐1). The mid‐left anterior descending coronary artery was occluded for 2, 10 and 2 min in four pigs, and for 2, 2, 5, 10 and 2 min in four other pigs. All the ischaemic periods were separated by 30 min of reperfusion and the biopsies were obtained 60 min after the last ischaemic period. Segment length function was measured in the ischaemic region and in the control region supplied by the left circumflex artery. In the two groups, the percentage systolic shortening was reduced equally, to 59±9 and 58±10% of control in the region subjected to ischaemia and only minimally in the control region. The biopsies from the stunned region from both groups showed: (1) no change in either the affinity for carbachol or the number of binding sites of the muscarinic receptors; (2) no alterations in messenger RNA encoding for the α subunit‐2 of the inhibitory guanine nucleotide binding protein, as demonstrated by northern blot and solution hybridization; (3) no change in membrane‐bound inhibitory guanine nucleotide binding protein, as shown by enzyme immunoassay utilizing a specific anti‐peptide antibody, and (4) unchanged inhibition of stimulated adenylyl cyclase activity. These results suggest that there is an intact inhibitory guanine nucleotide binding protein‐mediated muscarinic receptor adenylyl cyclase system in the stunned porcine myocardium.
Pressure‐induced local venous constrictor responses in human fingers
Authors: HEYMAN F. , STRID K.‐G.
Published: December 2008

Particularly in humans, systemic veins are often exposed to extensive changes in transmural pressure at altered body positions, when centrally conveyed constrictor reflexes provide compensation to maintain a proper venous return. The present aim was to explore whether also purely local mechanisms, of e.g. myogenic and/or axon reflex nature and operating at the venular‐small vein levels, may contribute to offset venous pooling at local pressure increases. For such purposes the capacitance vascular responses were recorded plethysmographically in human fingertips, as most of the blood content is here contained in venules and small veins. Local increases in transmural pressure, induced by graded venous outflow obstructions, first induced a corresponding passive‐venous distension which within a few seconds was followed by a venoconstrictor response that could return the local blood content to nearly control level within 25–35 s. On sudden release of venous obstruction this ‘active’ response was unmasked as a prompt volume ‘undershoot’ that subsided in another 15–30 s. These microvascular responses could be powerful enough almost to offset the venodistension caused by transmural pressures up to 90–100 mmHg, and at brisk pressure increases they could be quite rapid in onset. As general reflex influences seemed to be excluded, these results in humans suggest that also the capacitance microvessels, like the precapillary resistance ones, can display myogenic responses to offset pressure increases. As the venular‐small vein compartment contains up to 40% of the total blood volume such local responses, if generalized, may importantly contribute to venous control in humans.
Inhibition of neuropeptide Y‐induced augmentation of noradrenaline‐induced vasoconstriction by D‐myo‐inositol 1,2,6‐trisphosphate in the rat mesenteric arterial bed
Authors: RALEVIC V. , EDVINSSON L. , BURNSTOCK G.
Published: December 2008

The effect of the neuropeptide Y antagonist D‐myo‐inositol‐l,2,6‐trisphosphate (α‐trinositol) was tested against modulatory actions mediated by neuropeptide Y in the isolated rat mesenteric arterial bed. Neuropeptide Y (1 and 10 nM) had no direct postjunctional effects, but augmented vasoconstrictor responses to noradrenaline and to sympathetic nerve stimulation to an extent which was greater with the higher concentration of neuropeptide Y. The augmenting effect of neuropeptide Y at 1 nM on vasoconstriction induced by lower doses of noradrenaline was antagonized by α‐trinositol (1μM), producing a shift to the right of the dose‐response curve. A lower concentration of α‐trinositol (0.1μM)had no inhibitory effect on responses to noradrenaline. Augmentation by the higher concentration of neuropeptide Y (10 nM) of noradrenaline‐induced vasoconstriction was not affected by α‐trinositol at concentrations of up to 10μM. α‐Trinositol did not significantly antagonize neuropeptide Y‐induced augmentation of vasoconstrictor responses to sympathetic nerve stimulation, α‐Trinositol alone did not affect vasoconstrictor responses to noradrenaline, potassium, or to sympathetic nerve stimulation. In the raised‐tone preparation (tone raised with methoxamine) in the presence of guanethidine (5μM) to block sympathetic neurotransmission, perivascular nerve stimulation caused vasodilatation due to activation of sensory‐motor nerves. Neuropeptide Y inhibited sensory‐motor nerve induced vasodilatation in a concentration‐dependent manner but this was not affected by α‐trinositol (1μM). These results suggest that α‐trinositol can be a useful functional antagonist of neuropeptide Y‐induced augmentation of vasoconstrictor responses to noradrenaline in the rat mesenteric arterial bed. Antagonistic effects of α‐trinositol on neuropeptide Y‐mediated pre‐junctional inhibition of sensory‐motor neurotransmission were not evident.
Ventilatory responses at the onset of passive movement and voluntary exercise with arms and legs
Authors: ISHIDA K. , TAKAISHI T. , MIYAMURA M.
Published: December 2008

This study was undertaken to elucidate whether phase I appeared at the onset of voluntary and passive arm movements and to compare these results with those of similar leg movements. Instead of the conventional cranking exercise, seven male subjects performed alternately flexion‐relaxation of both arms, extension‐relaxation of both legs, and combined arm and leg exercise at the rate of about 60 min‐1 for four breaths in a sitting position. Similar movements were accomplished passively by the experimenters. In all experiments, minute ventilation increased rapidly within the first breath after the onset of exercise. The difference of ventilation (delta value) between the mean of the first two breaths at the onset of voluntary exercise and that of five breaths during rest was significantly (P < 0.05) greater in arm (7.751 min‐1) than in leg (5.191 min‐1). Passive movement showed a similar tendency. Arm delta ventilation correlated highly (r = 0.74 ± 0.91) with leg delta ventilation and the slope of the regression lines was about 1.2. Heart rate increased abruptly while cardiac output did not always increase rapidly at the onset of locomotion. Oxygen uptake in the voluntary leg exercise continued for 3 min was slightly but nonsignificantly higher than in the arm exercise, indicating the equality of the exercise intensity. In conclusion, ventilatory responses at the onset of the arm exercise are larger than those of the leg in both voluntary and passive conditions regardless of the muscle mass, suggesting the different neurogenic mechanism between arm and leg.
Lowering Cortisol enhances growth hormone response to growth hormone releasing hormone in healthy subjects
Authors: DINAN T. G. , THAKORE J. , O'KEANE V.
Published: December 2008

Cortisol is known to influence growth hormone release probably by modulating somatostatin tone. We examined the effect of metyrapone (the 1 β‐hydroxylase inhibitor) treatment on growth hormone response to growth hormone releasing hormone (1 μg kg‐1 body wt). Six healthy male subjects were tested on two occasions 1 wk apart. On one occasion they received metyrapone followed by growth hormone releasing hormone and on the other placebo followed by growth hormone releasing hormone. In all subjects metyrapone produced a significant drop in Cortisol levels. Together with this drop there was a significant enhancement of growth hormone response to growth hormone releasing hormone. The GH response was negatively correlated with the Cortisol level. Growth hormone release in response to growth hormone releasing hormone challenge is thus seen to be heavily influenced by Cortisol levels.
Cooling effects on the histaminergic response of rabbit ear and femoral arteries: role of the endothelium
Authors: FERNÁNDEZ N. , GARCÍA‐VILLALÓN A. L. , BORBUJO J. , MONGE L. , GARCÍA J. L. , GÓMEZ B. , DIÉGUEZ G.
Published: December 2008

The effects of cooling on the isometric response of rabbit isolated central ear (cutaneous) and femoral (non‐cutaneous) arteries to histamine were determined at 37oC and 24oC (cooling). Under resting tension, both types of arteries contracted to histamine (10‐7‐10‐3M), and the sensitivity of ear arteries, but not of femoral arteries was lower at 24 than at 37oC. Chlorpheniramine (10‐7M) blocked the contraction of both types of arteries to histamine at both temperatures. In ear arteries, endothelium removal or treatment with the nitric oxide synthase inhibitorNG‐nitro‐L‐arginine methyl ester (L‐NAME, 10‐5M) did not affect the contraction to histamine at 37oC, but it reversed the decreased contraction at 24oC. In femoral arteries, endothelium removal or L‐NAME (10‐5M) did not affect the response to histamine at 37 and 24oC. Ear and femoral arteries precontracted with endothelin‐1 (10‐8‐10‐7M) and pretreated with chlorpheniramine (10‐5M) relaxed to histamine (10‐7‐10‐4M), and the sensitivity of this relaxation in ear arteries, but not in femoral arteries, increased at 24oC. The relaxation of ear and femoral arteries to histamine was not modified by endothelium removal, L‐NAME (10‐5M) or meclofenamate (10‐5M), but it was blocked by cimetidine (10‐6M) at 37oC and 24oC. These results suggest: (1) ear and femoral arteries have contracting H1and relaxing H2receptors, probably located on smooth musculature, and (2) cooling reduces the contraction and increases the relaxation of cutaneous arteries to histamine: the reduction of this contraction could be caused by an augmented availability of endothelial nitric oxide, and the increment of this relaxation could be caused by an augmented sensitivity of H2receptors of smooth musculature induced by cooling. These features do not seem to occur in deep vessels.
Role of vagal nerve activity during suckling. Effects on plasma levels of oxytocin, prolactin, VIP, somatostatin, insulin, glucagon, glucose and of milk secretion in lactating rats
Authors: ERIKSSON M. , BJÖRKSTRAND E. , SMEDH U. , ALSTER P. , MATTHIESEN A.‐S. , UVNÄS‐MOBERG K.
Published: December 2008

The aim of this study was to investigate the role of vagal nerve activity for the release of oxytocin, prolactin and gastrointestinal (GI) hormones during suckling as well as for the secretion of milk in lactating rats. We have therefore performed experiments on vagotomized lactating rats. The animals were decapitated and trunk blood was collected from nonsuckling rats and from suckling rats in connection with milk ejection. Oxytocin, prolactin, vasoactive intestinal polypeptide (VIP), somatostatin, insulin, glucagon and glucose levels in plasma were measured by RIA‐technique. In addition, maternal weight as well as the weight of the litters were recorded 7 d after vagotomy. As expected, oxytocin and prolactin levels rose in response to suckling in sham‐operated controls. In vagotomized animals the suckling‐induced increase of oxytocin was blocked and prolactin levels were significantly decreased. VIP levels in plasma increased following suckling in sham‐operated animals and failed to respond after vagotomy. In contrast, somatostatin levels that rose significantly in sham‐operated rats were even more significantly raised in vagotomized animals. In addition, insulin but not glucagon levels were increased by suckling. The insulin response, however, persisted after vagotomy. Interestingly, suckling was followed by a lowering of blood‐glucose levels in vagotomized, but not in sham‐operated animals. The vagotomized rats ate as much and increased in weight as sham‐operated rats during the 7 d of vagotomy. The litters of vagotomized rats, however, gained significantly less weight in comparison with control litters. In conclusion, this study shows that vagal nerve activity is of importance for the release of oxytocin, prolactin, vasoactive intestinal polypeptide and somatostatin during suckling. In addition, vagal nerve activity was found to be of fundamental importance for adequate milk secretion, since litters of vagotomized rats increased in weight less than litters of sham‐operated operated animals.
Reducing brain sodium concentration prevents post‐prandial and dehydration‐induced natriuresis in sheep
Authors: MCKINLEY M. J. , HARVEY R. B. , VIVAS L.
Published: December 2008

Renal Na excretion during the 24 h following feeding was studied in sheep. A pronounced natriuresis occured 3.5‐5.5 h after feeding. Na excretion then fell to low levels in animals allowed to drink water, but was significantly elevated above this level in water‐deprived sheep for most of the remaining period. Both the post‐prandial and dehydration‐induced natriuresis were prevented by intracerebroventricular (icv) infusions of low Na concentration 0.3 mol 1‐1 mannitol at 1 ml h_1, and a water diuresis also occurred. These effects were not caused by icv infusion of artificial cerebrospinal fluid (Na concentration = 150 mmol l‐1). As a result, there was a much greater increase in plasma Na concentration and osmolality in the sheep given icv mannitol. Intravenous infusion of vasopressin prevented the water diuresis induced by icv mannitol, but the inhibition of natriuresis was still observed and plasma Na concentration increased by 8 mmol l‐1 over 24 h compared with an increase of 3 mmol l‐1 in dehydrated sheep infused icv with artificial cerebrospinal fluid. The results show that the ambient Na concentration in the brain plays an important role in the normal homeostatic regulation of Na balance by the kidney in sheep.
Effects of endothelin, calcium channel blockade and EDRF inhibition on the contractility of human uteroplacental arteries
Authors: FRIED G. , LIU Y.‐A.
Published: December 2008

In order to examine the possibility that endothelin might be important in the regulation of placental blood flow, human uteroplacental vessels were superfusedin vitroto study the contractile effect of endothelin as compared with a known strong contractor of placental blood vessels, serotonin (5‐HT). The contractile responses were compared in the presence and absence of calcium channel blocking agents, as well as in the presence of L‐NMA, an inhibitor of EDRF/nitric oxide. Endothelin (ET, 10‐510‐6M) and 5‐HT (10‐8‐10‐4M) induced contractions in the vessels. Maximal contractions in the presence of endothelin were elicited at 10‐7M, whereas 5‐HT elicited maximal contractions at 10‐5M. At 10‐7M, ET was more potent than 5‐HT. The calcium‐channel blocking agents nifedipine, diltiazem and NiCl2relaxed the vessels by 5–15% from baseline. The contractile response to ET in the presence of nifedipine or diltiazem was reduced by 55 and 67%, respectively. The response to 5‐HT in the presence of nifedipine was reduced by 58%. The contractile response to 5‐HT as well as ET in the presence of both nifedipine and NiCl2was not significantly lower than in the presence of nifedipine only. The EDRF‐inhibiting agent L‐NMA caused a small contractile response at concentrations of 10‐6–10‐5M. ET as well as 5‐HT added after pretreatment with L‐NMA produced a larger contractile response than ET or 5‐HT alone. The results show that ET has a strong contractile effect on placental blood vessels at concentrations likely to occur during labor and delivery. The mechanism whereby ET as well as 5‐HT contracts placental vessel smooth muscle appears to partly involve nifedipine‐ and diltiazem‐sensitive calcium channels, but almost half of the response depends on mobilization of calcium through other means.
Interferon‐induced class II expression at the spongiotrophoblastic zone of the murine placenta is linked to fetal rejection and developmental abnormalities
Authors: VASSILIADIS S. , TSOUKATOS D. , ATHANASSAKIS I.
Published: December 2008

Type II interferon is known to induce a plethora of gene expression involved in the humoral and cellular immunity. One of the multiple sites of action of γ‐IFN is the fetoplacental unit, where its role has not yet been clearly defined. We have previously shown in vitro that γ‐IFN may induce expression of class II MHC antigens on the spongiotrophoblast layer of the murine placenta, which under physiological conditions is negative for these antigens. Indeed, the absence of class II antigens from the placenta could be part of a mechanism evoked by fetal tissues to escape a host vs. graft reaction. In the present study we show that intraperitoneal in vivo administration of low doses of recombinant γ‐IFN to pregnant females specifically induces class II antigens on the spongiotrophoblast zone, increases fetal abortion, causes retardation of eye development in the fetuses and decreases fetal weight. This treatment also affects the maternal pathology as we witness a prominent hypersplenism in the mother accompanied by low levels of haematocrit, elevated IgG production and decreased granulocytic and thrombocytic counts. These results are specifically linked to the pregnant state of the mother, since virgin females do not develop any of the above abnormalities.

Our results not only point to a new dimension in γ‐IFN's role during pregnancy, but may be of clinical importance for prophylaxis since administration of γ‐IFN to a pregnant female may lead to abortion, fetal abnormalities or cause haematologic disorders to the mother.
Intrafascicular recordings of afferent multi‐unit activity from the human supraorbital nerve
Authors: NORDIN M.
Published: December 2008

Intrafascicular recordings of afferent multi‐unit activity were obtained from the supraorbital nerve in 40 healthy human volunteers, using tungsten micro‐electrodes inserted percutaneously at the eyebrow. Seventy‐seven fascicular receptive fields were mapped; their area ranged from 2 to 76 cm2, with a median of 19 cm2. The smallest fields were found in the eyebrow region, and the largest on the scalp. In response to non‐painful electrical intradermal stimulation, the conduction velocity of the fastest nerve fibres was calculated to be 40 ± 2 m s‐1 (mean ± SEM), and the later part of the afferent volley corresponded to a velocity of 20 ± 1 m s‐1. The responses to skin indentation indicated that the density of mechanoreceptive innervation was higher in the lower part of the forehead than in the upper/posterior part of the innervation territory of the nerve. A rapid mechanical tap on the forehead and scalp evoked two major afferent volleys corresponding to the on‐ and off‐phase of the stimulus. Manipulation of hairs resulted not only in dynamic responses to hair movement, but also in a static discharge during sustained hair displacement. When a fascicular field included the eyebrow region, skin stretching during blinking movements evoked distinct afferent activity. Following mechanical and electrical stimuli there were no signs of ‘trigeminal antidromic potentials’ of the type described in the cat and monkey.
Renal handling and plasma elimination kinetics of carbonic anhydrase isoenzymes I, II and III in the rat
Authors: ÖJTEG G. , WISTRAND J.
Published: December 2008

Using a radio‐immunosorbent technique, the levels of the carbonic anhydrase (CA) isoenzymes CA I, II and III in plasma (1–3 μ ml‐1), lymph (0.5‐1.6 μg ml‐1) and urine (0.03‐0.06 ± 3, 42 ± 11 and 35 ± 4 nl min‐1 (g kidney wet wt)‐1 (n = 4–5), respectively. After a single i.v. injection of purified native or 125I‐labelled isoenzymes, the elimination of CA I, and CA III from plasma followed a bi‐exponential decline, with half‐times of 7 and 9 min for the rapid phase and 112 min for the slow phase, respectively. Nephrectomy decreased the rapid phase and the build‐up of catabolites. Therefore, the rapid phase of CA I and III elimination is probably explained by filtration of unbound isoenzyme at the glomeruli and subsequent degradation by the proximal tubules. The plasma elimination curve for CA II was different and followed a mono‐exponential decline, with a half‐time of 210 min both in normal and nephrectomized animals. This indicates that CA II is not filtered at the glomeruli. However, in acute renal failure, with leaking tubular cells, CA II was excreted into the urine. The slow elimination of the major part of the isoenzymes from plasma is explained by the binding of CA I, II and III to a plasma protein, immunochemically similar to transferrin, forming a macromolecular complex with a mol wt of 114 ± 2 kDa.
Chromogranin A: a multipurpose prohormone?
Authors: HELLE K. B. , ANGELETTI R. H.
Published: December 2008

This minireview aims to discuss the new evidence for a multipurpose prohormone function for chromogranin A, the index member of the chromogranin/secretogranin family of universally distributed, uniquely acidic proteins.
Factors limiting force during slow, shortening actions of the quadriceps femoris muscle group in vivo
Authors: HARRIS R. T. , DUDLEY G. A.
Published: December 2008

Speed‐torque relations of the quadriceps femors muscle group were determined using eight healthy subjects. Isometric or isovelocity, shortening muscle actions were performed at 15 speeds (0–6.28 rad s‐1) and torque was measured 0.78 and 0.52 rad below horizontal. Unilateral actions were evoked by surface electrical stimulation or by maximal voluntary effort. Stimulation current evoked a torque equal to approx. 70% of maximal voluntary isometric and was held constant across speeds. For the voluntary or stimulation tests, torque decreased (P < 0.05) with increasing speed. This response in relative terms was greater (P < 0.05) for the stimulation than for the voluntary tests. The difference in the decline in relative torque for the simulation vs. voluntary tests was not influenced by the angle at which torque was measured, and thereby muscle length. Speed‐torque data for the two stimulation tests fit a linearized plot of a hyperbolic relation for the higher tests speeds. When torque was measured at the greater joint angle (0.78 rad), and thereby longer muscle length, the equation was Po – P/V = Po 0.724‐1.078 (p<0.05, r2= 0.95) for speeds greater than 0.70 rad s‐1. For the shorter muscle length, the equation for data collected at speeds greater than 1.13 rad s“1 was Po‐P/V = Po 0.467 + 4.61 (P < 0.05, r2= 0.91). Inclusion of data for the next slower speed markedly compromised the ‘fit’ for either linear relation. The results suggest that the extent of force limitation by ‘some neural inhibitory mechanism’ during maximal voluntary effort has previously been over‐estimated because the speed‐torque relation for the quadriceps femoris muscle group was not hyperbolic in nature at ‘slow’ speeds when involuntary, shortening actions were studied. The magnitude of force limitation does not, however, appear to depend on muscle length.
Participation of prostaglandins and bradykinin in the effects of angiotensin II and converting enzyme‐inhibition on sympathetic neurotransmission in vivo
Authors: SCHWIELER J. H. , KAHAN T. , NUSSBERGER J. , HJEMDAHL P.
Published: December 2008

We investigated the mechanism(s) by which angiotensin converting enzyme (ACE)‐inhibition and angiotensin (Ang) II influence peripheral sympathetic neurotransmission in canine gracilis musclein situ, with a‐adrenoceptors either intact or irreversibly blocked by phenoxybenzamine. ACE‐inhibition by ramiprilat reduced, and subsequent infusion of Ang II (30 ng kg‐1min‐1i.v.) markedly increased arterial plasma Ang‐(1–8)octapeptide levels, basal muscle perfusion pressures and mean arterial pressure. Local intra‐arterial bolus injection of Ang II caused marked vasoconstriction followed by vasodilation. This vasoconstrictor response was enhanced and the ensuing vasodilation was abolished following prostaglandin synthesis inhibition by diclofenac. The vasoconstrictor response to low frequency (0.5 Hz) sympathetic nerve stimulation was also enhanced by diclofenac. The nerve stimulation‐evoked noradrenaline (NA) overflow was reduced by ramiprilat when a‐adrenoceptors were blocked (‐ 11 ± 3 %,P <0.05), but increased when a‐adrenoceptors were intact (+ 28± 14%,P <0.05). During ACE‐inhibition, effective bradykinin receptor antagonism by HOE 140 reduced stimulation‐evoked NA overflow irrespective of a‐adrenoceptor blockade (i.e. by 25 ± 5 and 20 ± 3% in the absence and presence of a‐adrenoceptor blockade, respectively,p< 0.01). Diclofenac increased stimulation‐evoked NA overflow in the absence of a‐adrenoceptor blockade (+ 19 ± 4%,P <0.05). I.v. infusion of Ang II failed to enhance stimulation‐evoked NA overflow both before and after diclofenac.

In conclusion, the results support the ideas that local formation of Ang II and bradykinin facilitate, and of prostaglandins inhibit NA release, and that ACE inhibition influences sympathetic neurotransmission through all of these mechanisms in skeletal musclein situ;the net result depends on the degree of prejunctional a‐adrenergic feedback inhibition. Circulating Ang II may enhance the local formation of vasodilatory prostaglandins, but does not seem to modulate NA release even after prostaglandin synthesis inhibition in this model. Our data suggest that circulating Ang II may not reach the perivascular sympathetic nerves to a significant extent in skeletal musclein vivo.
Endothelium‐dependent relaxation resistant to N/ω‐nitro‐L‐arginine in the rat hepatic artery and aorta
Authors: ZYGMUNT P. M. , GRUNDEMAR L. , HÖGESTÄTT E. D.
Published: December 2008

Nitric oxide (NO)‐independent pathways contributing to acetylcholine (ACh)‐induced relaxation were examined in the rat isolated hepatic artery and aorta at low and high levels of precontraction induced by phenylephrine (PhE). In the hepatic artery, the ACh‐induced relaxation was unaffected by the NO synthase inhibitors Nw‐nitro‐L‐arginine (L‐NOARG, 0.3 mM) and Nω‐nitro‐L‐arginine methyl ester (0.1 mM) at either level of pre‐contraction. In the aorta, L‐NOARG virtually abolished the ACh‐induced relaxation at a high level, but only partially reduced the response at a low level of precontraction. Methylene blue (10 μM) and indomethacin (10 μM) did not affect the ACh‐induced relaxation in the hepatic artery. L‐NOARG completely inhibited the cGMP and cAMP increases induced by ACh in both types of artery. In the presence of L‐NOARG, ACh was unable to relax the hepatic artery precontracted by K+. The sensitivity to PhE was increased less by L‐NOARG (threefold) than after endothelial denudation (tenfold) in the hepatic artery, whereas no such difference was observed in the aorta. The relaxation induced by the NO donor 3‐morpholino‐sydnonimin did not differ between the arteries after endothelial denudation. These results are compatible with the existence of an endothelium‐dependent inhibitory pathway distinct from the NO and cyclooxygenase pathways. This pathway seems to contribute more to the ACh‐induced relaxation in the hepatic artery than in the aorta, whereas the opposite appears to be true for the NO pathway.
Pituitary adenylate cyclase activating polypeptide induces vascular relaxation and inhibits nonvascular smooth muscle activity in the rabbit female genital tract
Authors: STEENSTRUP B. R. , OTTESEN B. , JØRGENSEN M. , JØRGENSEN J. C.
Published: December 2008

In vitro effects of two bioactive forms of pituitary adenylate cyclase activating polypeptide (PACAP): PACAP–38 and PACAP–27 were studied on rabbit vascular and non–vascular smooth muscle. Segments of the ovarian artery and muscle strips from the fallopian tube were used. Two series of experiments were performed on vessels: the dose–response relationship of PACAP–38 (10–10–7 M) was established on noradrenaline– (NA, 10–6 M) contracted vessels. In the other set of experiments the contractile effect of 10–8–10–4 M NA added cumulatively, was studied on arterial segments incubated with PACAP–38 (10–7 M), PACAP–27 (10–7 M) or VIP (10–7 M). The effect of PACAP–38, PACAP–27 and VIP (10–10–10–6 M) was investigated on spontaneously contracting smooth muscle of the fallopian tube. Longitudinally as well as transversally cut specimens were investigated. PACAP–38 produced a significant dose–related relaxation on the NA–precontracted vessels. However, pre–incubation of the vessels with 10–7 M PACAP–38, PACAP–27 and vaso active intestinal polypeptide (VIP) did not induce a general rightward shift of the NA concentration–response curves, although a tendency to inhibition in the low–dose interval was observed. The peptides caused a significant, dose–dependent inhibition of both frequency and amplitude on the fallopian tube smooth muscle activity. The effects of the three peptides on longitudinally as well as transversally cut specimens were alike.
Moderate fatigue studied at great sarcomere lengths in frog single muscle fibres
Authors: LOU F. , SUN Y.–B.
Published: December 2008

Single fibres from the anterior tibialis muscle of Rana temporaria (temperature, 2–3 oC) were moderately fatigued at a prestretched sarcomere length (approximately 3.6 μm) by reducing the intervals between 2 s tetani from 240 to 20 s. Changes in length of marked segments along the muscle fibre were monitored during fixed–end tetani using a photoelectric recording system. In contrast to the situation at 2.2 μm sarcomere length, the central region of the fibre was elongated during tetanus at the prestretched fibre length, whereas the segments next to the fibre–tendon junctions (end segments) shortened correspondingly. These length changes were associated with a slow climb of force (tension creep). During development of fatigue, the maximum tetanic tension was reduced to about 78% of the control value and the time course of the tetanus was markedly changed. The tension creep observed in control tetanus was greatly reduced during fatigue, the tetanic tension remaining nearly constant after an initial rising phase. The change in shape of the force myogram during fatigue was associated with a considerable reduction in the amplitude of segment movements along the fibre. The results are explainable by assuming that the end segments (having shorter sarcomeres) become more fatigued than other parts in series along the fibre. At the same time the central segments are likely to have acquired a higher ability to resist stretch by the end segments.