bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasoinhibitory activity of synthetic peptides from the amino terminus of chromogranin A
Authors: ANGELETTI R. H. , AARDAL S. , SERCK‐HANSSEN G. , GEE P. , HELLE K.B.
Published: December 2008

Naturally occurring amino terminal fragments of chromogranin A (CGA), the calcium‐binding protein found in all endocrine secretory vesicles, have vasoinhibitory activity when tested in isolated segments of the endothelium‐denuded human saphenous vein. Synthetic peptides corresponding to sequences within the first 76 residues of chromogranin A have been made and tested for biological activity. Full length vasostatin I (CGA1–76) (40 nM), but not the truncated vasostatin I, CGA1–40(100 nM) mimics natural chromogranin A fragments in its inhibition of contractions induced by endothelin‐1 (ET‐1) in calcium containing medium. CGA1–40(100 nM) mimics the inhibitory effect of the vasostatins on the contractions induced in the absence of extracellular calcium by high potassium and noradrenaline, but not by ET‐1. The iodinated peptides both exhibit saturable binding in an aortic smooth muscle cell line, indicative of a single class of high affinity binding protein (‘receptor’ with an apparent KDof approximately 45 nM. This binding is not affected by endothelin‐1. Iodinated peptides can be crosslinked to a single polypeptide in binding experiments performed on intact calf aortic smooth muscle cells.
Repeatable measurement of local and zonal GFR in the rat kidney with aprotinin
Authors: TENSTAD O. , WILLIAMSON H.E. , AUKLAND K.
Published: December 2008

The basic polypeptide aprotinin (Ap), mol. wt 6513, is freely filtered in glomeruli and completely reabsorbed by the proximal tubules. Cellular processing is slow with return to plasma of breakdown products beginning after 20–30 min. When corrected for Gibbs‐Donnan distribution of Ap between glomerular filtrate and plasma (i.e. 0.65 at a plasma protein concentration of 50 mg ml‐1), the renal clearance of [125I]Ap, estimated as the ratio of kidney uptake and integrated non‐protein bound plasma 125I concentration, equals that of [61Cr]EDTA (urine + kidney content). Zonal GFR per gram tissue was obtained from uptake in three to six samples from outer and inner cortex (OC, IC) and the cortico‐medullary border zone, 5–30 min after i.v. injection in rats. Control GFR in OC was 2.05 (SD 0.39) ml g'1 min1 and the IC/OC ratio 0.66 (SD 0.14). Repeated local clearances (C, and C,) were obtained by injecting a second tracer (i.e. [131I]Ap) 15 min after the first injection (i.e. [125I]Ap), which by then had a low plasma concentration. The kidneys were removed at 30 min, frozen and dissected. During control conditions Cn/C, averaged 1.06 in OC and IC, and the coefficient of variation (CV) between CII/CI ratios of individual tissue samples was 2% in both zones. Lowering left renal arterial pressure before the second injection reduced GFR proportionally in both zones (34 and 37%) with a CV of intersample C11/C11, ratios of 5%. We conclude that the method allows precise and repeatable measurements of local and zonal GFR.
Glomerular filtration and tubular absorption of the basic polypeptide aprotinin
Authors: TENSTAD O. , WILLIAMSON H. E. , CLAUSEN G. , ØIEN A. H. , AUKLAND K.
Published: December 2008

The basic polypeptide aprotinin (Ap), mol. wt 6500, pi 10.5, is filtered in the glomeruli, virtually completely taken up by the proximal tubular cells and retained there for many hours. This process was studied in rats by determining the renal plasma clearance (CAp) as the amount of [126I]Ap accumulated in the kidney plus that excreted in the urine per unit of time divided by the integrated plasma concentration. In periods lasting 4–20 min after i.v. bolus injection or infusion to constant plasma concentration, CAp was 65% of glomerular filtration rate (GFR) estimated as kidney plus urinary clearance of [51Cr]EDTA (CCr.EDTA). Less than 0.8% of the filtered Ap appeared in the urine. CAp varied inversely with plasma protein concentration in mgml“1: CAp/CCrEDTA= 0.98‐0.0058 × PPr, corresponding to a glomerular Gibbs‐Donnan distribution for a net molecular charge of + 6, in agreement with the amino acid composition of Ap. CAp (kidney + urinary) was not altered by inhibiting tubular uptake of [125I]Ap by maleate or by exceeding the uptake capacity with large doses of unlabelled Ap. Neutralized Ap (malonylated) did not accumulate in the kidney, but showed a urinary clearance indistinguishable from that of [51Cr]EDTA. Both CAp and C(.rEDTA were reduced to 0.04 ml min‐1 when glomerular filtration pressure was lowered by ureteral stasis and increased PPr (80–90 mg ml”1). These findings indicate: (1) no steric or charge restriction to filtration of Ap in the glomerular membrane, (2) the Gibbs‐Donnan equilibrium should be considered when estimating glomerular sieving of charged polypeptides in intact animals (3) charge dependent tubular uptake, (4) little or no transtubular transport of intact Ap, (5) no appreciable tubular uptake of Ap from the peritubular side and (6) local renal accumulation of Ap in a period of up to 20 min may be used to estimate local glomerular filtration and/or local proximal tubular reabsorption rates.

Model analysis based on the appearance of 125I in plasma, the time course of renal Ap content, and literature data on subcellular Ap distribution are consistent with two populations of endosomes, transporting Ap at widely different rates from the proximal tubular brush border to the lysosomes where breakdown occurs at a high rate.
Electrophoretic analysis of cat parotid saliva in response to parasympathetic stimulation or infusion of bethanechol
Authors: EKSTRÖM J. , MARSHALL T. , TOBIN G. , WILLIAMS K. M.
Published: December 2008

The protein constituents of cat parotid saliva evoked by parasympathetic stimulation or the infusion of bethanechol have been compared by sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE). The SDS‐PAGE patterns were highly reproducible for an individual cat and revealed up to 30 polypeptide bands in microlitre volumes of unconcentrated saliva. Only minor and predominantly quantitative differences were detected in the salivary protein composition of different cats. SDS‐PAGE demonstrates quantitative rather than qualitative changes in the protein composition of saliva evoked in response to different stimuli. The latter included preliminary observations on the effect of vasoactive intestinal peptide (VIP) on the bethanechol‐evoked response.
Light–dependent effects of zinc protoporphyrin IX on endothelium–dependent relaxation resistant to NoM–nitro–L–arginine
Authors: ZYGMUNT P. M. , HÖGESTÄTT E. D. , GRUNDEMAR L.
Published: December 2008

Acetylcholine (ACh) induces an Nω–nitro–L–arginine (L–NOARG)–resistant relaxation and hyperpolarization in the rat isolated hepatic artery. The possibility that carbon monoxide (CO) produced by haem oxygenase (HO) is an endogenous mediator of this response was investigated. Exogenously applied CO evoked a concentration–dependent relaxation, and the CO ‘scavenger’ oxyhaemoglobin (10μM) reduced the maximum ACh–induced relaxation by 25%. The HO inhibitor zinc protoporphyrin IX (ZnPP, 10 μMvirtually abolished the ACh–induced relaxation in experiments carried out under ordinary light conditions. However, ZnPP did not affect the ACh–induced relaxation under dark conditions, even after exposure of ZnPP to intense light before the preincubation period. Biliverdin (0.1 mM), a feedback inhibitor of HO, was also inactive under dark conditions, and the HO substrate haematin (0.1 mM) did not facilitate the ACh–induced relaxation. The relaxation induced by the nitric oxide (NO) donor 3–morpholino–sydnonimin was not affected by ZnPP in the presence of light. However, ZnPP inhibited the relaxation evoked by the potassium channel opener levcromakalim and the tonic component of the contractile response to 60 mM potassium, indicating that ZnPP has effects distinct from HO inhibition in the presence of light. ZnPP should therefore be protected from light when used to inhibit HO–mediated CO formation. The results do not suggest that CO generated by HO mediates the endothelium–dependent, L–NOARG–resistant relaxation induced by ACh in the rat hepatic artery.
Substrate transport and utilization in fish erythrocytes
Authors: NIKINMAA M. , TIIHONEN K.
Published: December 2008

In contrast to mammalian erythrocytes which fulfil their energy requirements via anaerobic glycolysis, fish erythrocytes obtain most of their energy aerobically via the Krebs cycle. This enables them to use various substrates, including monocarboxylic acids, glucose and amino acids. This review discusses the membrane permeability of these substrates, and their relative importance in the energy production of fish erythrocytes. Agnathans are characterized by a high permeability to all of the potential substrates, glucose, monocarboxylic and amino acids. In contrast, teleost erythrocytes are often characterized by low glucose permeability. It appears that monocarboxylic acids and certain amino acids such as glutamine may be more important in energy production of teleost erythrocytes than glucose.
The evolution of hormonal sex pheromones in teleost fish: poor correlation between the pattern of steroid release by goldfish and olfactory sensitivity suggests that these cues evolved as a result of chemical spying rather than signal specialization
Authors: SØRENSEN P. W. , SCOTT A. P.
Published: December 2008

It is becoming increasingly evident that many teleost fish use hormones and their metabolites as sex pheromones. Although hormonal pheromone systems of several species of fish have now been characterized, that of the goldfish is the best understood. Reproductively–active female goldfish sequentially release derivatives of three steroidal hormones and two prostaglandins which have specific and potent actions on the goldfish olfactory sense and subsequently conspecific reproductive behaviour and physiology. Three goldfish hormonal pheromones are unmodified sex hormones which are also found in the blood of many other species offish and are therefore unlikely to be species–specific. This scenario evokes two related questions. First, how did these systems evolve? Second, do hormonal pheromones represent specialized signals used for communication or rather simple metabolites which fish have evolved the ability to detect because of their intrinsic meaning (‘spying’)? Here we review hormonal pheromone function in fish and then describe a study of the goldfish which tests whether hormonal pheromones are specialized communicatory signals by comparing the profile of steroids released by goldfish with their olfactory responsiveness to these compounds. Little correlation between signal production and detection was found and we conclude that the goldfish hormonal pheromone system most likely exemplifies spying.
Potentiation of concentric plantar flexion torque following eccentric and isometric muscle actions
Authors: SVANTESSON U. , GRIMBY G. , THOMEÉ R.
Published: December 2008

In a stretch‐shortening cycle (SSC) the concentric muscle action is enhanced by a preceding eccentric muscle action. The hypothesis of the present study is that a preceding isometric action can also have an effect on a following concentric action, but to a lesser degree. A KINetic‐COMmunicator II dynamometer was used to test muscle strength of the plantar flexion of the right foot in 20 healthy women. Maximal voluntary torque measurements were made at different angular velocities (120o s‐1 and 240o s‐1) and the range of motion of the ankle joint was 78–125o. The assessment was based on concentric torque output and EMG recording from the gastrocnemius muscle under three different types of testing conditions (concentric actions with and without preceding eccentric or isometric actions, all with maximal efforts). The results showed that preceding muscle actions led to greater concentric torque output (P < 0.01) between 90 and 99o plantar flexion. However, the increase in the concentric action was significantly (P < 0.01) larger with eccentric than with isometric preceding action, regardless of velocity. The EMG activity of the concentric action showed unchanged or lower values when preceded by a muscle action. In this model our conclusion is that the main reason for larger concentric torque values after a preceding muscle action is that time is sufficient for maximal muscle tension development; in addition, elastic energy is stored, particularly during the preceding eccentric action. Our results show that the effect of preceding muscle actions should be taken into account when measuring isokinetic muscle strength at relatively small angular movements.
Sprint‐training effects on some contractile properties of single skinned human muscle fibres
Authors: LYNCH G. S. , McKENNA M. J. , WILLIAMS D. A.
Published: December 2008

The effects of sprint training on the contractile properties of human muscle fibres obtained by needle biopsy were investigated. Individual fibres were mechanically skinned and activated by Ca2+‐ and Sr2+‐buffered solutions at pH 7.1, and allocated to distinct populations on the basis of their contractile characteristics. The majority of fibres sampled pre‐training could be separated into the three major fibre groups: Populations I (24/70, 34%), II (25/70, 36%) and III (18/70, 26%), which exhibited characteristics similar to those of histochemically classified type I, IIA and IIB fibres, respectively. The remainder (3/70, 4%) represented another fibre group, with intermediate characteristics. The muscle fibres were also activated by Ca2+ at a reduced pH of 6.6, to mimic the intracellular acidification that occurs during intense exercise. Lowering pH increased the threshold for contraction by Ca2+, reduced Ca2+ sensitivity, and increased the steepness of the force‐pCa relationship, in all fibres sampled from the three major fibre groups. Maximum force was not significantly reduced in any fibre population. In the post‐training sample, the three major fibre types were present in different proportions: Populations I (10/52, 19%), II (20/52, 38.5%) and III (11/52, 21%). Three other fibre groups sampled in low numbers exhibited contractile characteristics intermediate between Population I and Population II. Following sprint training all of the three main fibre populations exhibited higher thresholds for contraction by, and lower sensitivities to, Sr2+ but not Ca2+, compared with the fibres sampled pre‐training. Maximum force was significantly lower in Population II fibres after sprint training. At pH 6.6, post‐trained Population III fibres exhibited even lower Ca2+ sensitivity, with concomitant increases in the threshold for contraction and force‐pCa curve steepness.
Remodelling of the retinal arterioles in descending optic atrophy follows the principle of minimum work
Authors: ROSSITTI S. , FRISÉN L.
Published: December 2008

Mathematical modelling indicates that the minimum energy cost for blood flow is achieved when the arteries are arranged in a branching hierarchy such that the radii of the vessels are adjusted to the cube root of the volumetric flow (principle of minimum work). This is known to apply over several magnitudes of vessel calibres, and in many different organs, including the brain, in humans and in animals. This paper addresses the issue of remodelling of one and the same arterial network to long‐term changes in blood flow. This has not been studied previously in humans. We measured the radius of parent (r0) and branch segments (rl and r2) of the retinal arteriolar network in fundus photographs of six patients with blinding, non‐vascular retrobulbar optic nerve lesions, mostly traumatic in origin, before and after the development of descending optic atrophy. Attenuation of retinal arterioles is a well‐known phenomenon in descending optic atrophy, and is attributable to decreased metabolic demand secondary to loss of the retinal ganglion cells and their axons. On average, arteriolar diameters decreased by 15.2±17.7% (SD), with 95% confidence intervals of 18.7% and 11.7%; the radii decreased significantly (P= 0.0001) (n= 99). The area ratio of the bifurcations, defined as (r21+r22)r‐02, was 1.23±0.2 before, and 1.18±0.2 after optic atrophy (n= 36); the change of area ratio was not significant. The branching geometry of the retinal arteriolar network obeyed strictly the optimum branching rule of the principle of minimum work, or r30=r31+r32. Bifurcation exponents corrected for the Fåhræus‐Lindquist effect were ˜˜ 3 before optic atrophy and remained unchanged after remodelling of the arterioles. It is concluded that the branching of the retinal arterioles and their adaptation to long‐term changes in blood flow in descending optic atrophy obey the principle of minimum work.
The Na+, K+‐pump and muscle contractility
Authors: CLAUSEN T. , NIELSEN O.B.
Published: December 2008

In skeletal muscle, the excitation induced influx of Na+ and efflux of K+ may be sufficient to exceed the activity or even the capacity of the available Na+, K+‐pumps. This leads to a rise in intracellular Na+ and extracellular K+ Both events interfere with excitability and may present important limitations for the continuation of contractile activity. Furthermore, inhibition of the Na+, K+‐pump or reduction of the concentration of functional Na+, K+‐pumps decrease excitability and the maintenance of force during continued stimulation. Conversely, in muscles where contractile force is inhibited by exposure to high extracellular K+, acute stimulation of the Na+, K+‐pump with catecholamines, CGRP or insulin leads to a rapid recovery of force. The large passive fluxes of Na+ and K+ associated with excitation constitute the major drive on the activity of the Na+, K+‐pump, giving rise to up to 20‐fold stimulation of the transport rate. In keeping with this, training induces an upregulation of the total concentration of Na+, K+‐pumps in skeletal muscle. The activity and the capacity of the Na+, K+‐pump are important limiting factors determining the maintenance of excitability and contractile performance.
The endothelium mediates a nitric oxide‐independent hyperpolarization and relaxation in the rat hepatic artery
Authors: ZYGMUNT P. M. , WALDECK K. , HÖGESTÄTT E. D.
Published: December 2008

The rat hepatic artery responds to acetylcholine (ACh) with an endothelium‐dependent relaxation, which is unaffected by nitric oxide (NO) synthase and cyclooxygenase inhibition. The purpose of this study was to investigate whether the NO‐independent relaxation is caused by hyperpolarization of the smooth muscle cells. In vessels with endothelium ACh induced a hyperpolarization in the presence of 0.3 mM Nw‐nitro‐l‐arginine (l‐NOARG) and 10μm indomethacin. The hyperpolarization, which slowly decayed after an initial maximum, generally lasted for at least 20 min. ACh in contrast to levcromakalim failed to hyperpolarize the smooth muscle cells in endothelium‐denuded vessels. In vessels contracted by phenylephrine (PhE) ACh caused a concentration‐dependent hyperpolarization and relaxation, and both events occurred over the same concentration interval. Curve fitting using the Hill equation showed a close correlation between the hyperpolarization and the relaxation. Exposure to a 30 mM K+ solution abolished the hyperpolarization and suppressed the relaxation induced by ACh. Nimodipine did not affect the ACh‐induced hyperpolarization, whereas the relaxation induced by ACh and levcromakalim, but not that evoked by the NO donor 3‐morpholino‐sydnonimin, were attenuated. Glibenclamide had no effect on the ACh‐induced hyperpolarization and relaxation, but abolished the corresponding responses to levcromakalim. The results demonstrate a NO‐independent hyperpolarization and relaxation in the rat hepatic artery. The hyperpolarization and relaxation were endothelium‐dependent, and apparently causally related to each other, since interference with the hyperpolarization or the subsequent effector pathway inhibited the relaxation.
l‐Arginine‐induced hypotension in the rat: evidence that NO synthesis is not involved
Authors: JUN T. , WENNMALM Å.
Published: December 2008

l‐Arginine is the biological precursor for nitric oxide (NO). NO is formed continuously in endothelial cells and maintains a certain degree of vasodilator tone under physiological conditions. Although the formation of NO is not primarily controlled by precursor availability, the extent to which extra supplementation withl‐arginine may affect endothelial NO formation, and hence, vasodilator tone and systemic blood pressure, is not entirely clear. To address this issue, we infusedl‐arginine i.v. in anaesthetized normotensive rats pretreated withNG‐nitro‐l‐arginine methyl ester (l‐NAME, 50 or 200 mg‐1) and in untreated controls, under continued recording of mean arterial pressure (MAP). In control animalsl‐arginine (25 or 100 mg kg‐1min‐1) had no effect on systemic MAP (111 ± 3 mm Hg), whilel‐arginine (200 mg kg‐1min‐1) lowered MAP (to 70 ± 6mmHg). D‐Arginine (200 mg kg‐1min‐1) also induced hypotension; during infusion of D‐arginine MAP fell from 106 ± 4 to 64 ± 4 mm Hg. Pretreatment withl‐NAME (50 and 200mgkg‐1) elevated MAP to 140 ± 2 and 147 ± 3 mm Hg, respectively, but failed to affect the hypotensive response tol‐arginine; during infusion ofl‐arginine (200 mg kg‐1min‐1) in rats pretreated withl‐NAME (50 and 200 mg kg‐1) MAP fell to 86 ± 9 and 104 ± 6 mm Hg, respectively. Plasma levels of the NO metabolite, nitrate, were 18 ± 4 and 17 ± 3μmol l‐1, respectively, before and after infusion ofl‐arginine (200 mg kg‐1min‐1). Trapping of NO to haemoglobin (HbNO) could not be detected, either before or after infusion ofl‐arginine (200 mg kg‐1min‐1). We conclude that a high dose ofl‐arginine may act hypotensive in normotensive rats. This effect does, however, not seem to be based on an augmented formation of NO.
Hypercapnic vasodilatation in isolated rat basilar arteries is exerted via low pH and does not involve nitric oxide synthase stimulation or cyclic GMP production
Authors: YOU J. P. , WANG Q. , ZHANG W. , JANSEN‐OLESEN I. , PAULSON O. B. , LASSEN N. A. , EDVINSSON L.
Published: December 2008

The relaxant effect of hypercapnia (15% CO2) was studied in isolated circular segments of rat basilar arteries with intact endothelium. The nitric oxide synthase inhibitor nitro‐l‐arginine (l‐NOARG) and the cytosolic guanylate cyclase inhibitor methylene blue (MB), significantly reduced this relaxation by 54% and 70%, respectively. The effect ofl‐NOARG was completely reversed byl‐arginine. Blockade of nerve excitation with tetrodotoxin (TTX) had no affect on the 15% CO2elicited vasodilatation. Measurements of cGMP in vessel segments showed no significant increase in cGMP content in response to hypercapnia.l‐NOARG and MB, but not TTX, significantly reduced the basal cGMP content in cerebral vessels. Adding 1.5% halothane to the incubation medium did not result in a significant increase in cGMP content. Lowering the pH by cumulative application of 0.12 m HCl resulted in relaxation identical to that obtained by lowering the pH with 15% CO2. In vessel segments in which the endothelium had been removed beforehand 15% CO2induced relaxation that was not different from that seen in vessels with intact endothelium.l‐NOARG had no affect in endothelium denuded vessels. The results suggest that high CO2elicits vasodilatation of isolated rat basilar arteries by a mechanism independent of nitric oxide synthase (NOS) activity. The markedly reduced basal cGMP levels in cerebral vessels byl‐NOARG and MB suggest that there exists a basal NO formation in the cerebral vessel wall.
Excitability of the soleus H reflex during graded walking in humans
Authors: SIMONSEN E. B. , DYHRE‐POULSEN P. , VOIGT M.
Published: December 2008

The excitability of the soleus Hoffmann (H) reflex was measured in five healthy male subjects during graded treadmill walking. Uphill and downhill walking at an 8% grade as well as level walking were used to vary the demands for lengthening and shortening contractions of the soleus muscle. These changes were assumed to cause differences in control of the afferent input in the spinal cord and the voluntary output to the soleus muscle.

The H reflex was strongly modulated in all three walking conditions, high during the stance phase and low or absent during the swing phase. The shape of the modulations was, however, different. At uphill walking the reflex increased gradually during the whole stance phase and seemed to follow the soleus electromyogram (EMG) pattern closely. In the downhill condition the reflex excitability increased rapidly at heel strike like the soleus EMG and co‐contraction of the anterior tibial muscle was observed. At level walking a fast rise in reflex excitability was seen just after heel strike with low or absent soleus EMG.

Mean soleus EMG was lower during downhill than during uphill or level walking, but the mean H reflex amplitude was similar in all three conditions. However, when the H reflex was related directly to the EMG activity by linear regression the reflex gain was lower during uphill walking than in the two other conditions. Furthermore, the ratio between H reflex and EMG amplitude was high during the first half of the stance phase at level walking indicating an elevated reflex excitability independent of the voluntary motor output. It is therefore concluded that the modulation of reflexes during walking cannot be interpreted in terms of the idea of automatic gain compensation. The reflexes must be controlled specifically and independently during the different phases of the motor output to meet the mechanical requirements of the movement task. Most explicitly this was seen during downhill walking, where an elevated reflex excitability together with co‐contraction at the ankle joint seem to provide increased joint stiffness and security, when the kinetic energy of the body has to be brought under control at heel strike.
The effect of phencyclidine on [3H]GABA and [3H]fulnitrazepam binding in the brain of naive and handling‐habituated rats
Authors: LILLRANK S. M. , OJA S. S. , SARANSAARI P.
Published: December 2008

The effects of handling and handling combined with phencyclidine (PCP) treatment on GABAergic neurotransmission were studied in Sprague‐Dawley rats. The animal material consisted of handling‐habituated (HH, for 11 d), acutely handled (naive, N), handling‐habituated and PCP‐treated (10 mg kg‐1 i. p., HH+PCP) and acutely handled (naive) PCP‐treated (N+PCP) and unhandled ‘control’ rats. The binding of [3]GANA and [3H]flunitrazepam (FLU) was studied with membrances and the release of [3H]GABA with slices prepared from the striatum and frontal cortex. In the striatum the maximal binding capacity (Bmax) and the binding constant (KD was lower in N rats. KD constants of [3H]FLU were significantly lower in both brain areas in N rats than in HH rats. After PCP treatment both Bmax and KD for [3H]GAGA diminished. Neither handlign nor PCP had any effect on [3H]GABA release from striatal and frontal cortical slices. Handling prior to killing thus affects differently the GABAergic parameters studied and modulates the PCP‐induced effects
Phosphate metabolism of prior eccentrically loaded vastus medialis muscle during exercise in humans
Authors: RODENBURG J. B. , De GROOT M. C. H. , VAN ECHTELD C. J. A. , JONGSMA H. J. , BÄR P. R.
Published: December 2008

The possible alteration of metabolism of the m. vastus medialis was investigated during exercise after eccentric loading. Twelve male subjects performed stepping exercise for 25–60 min. One week before and 24 h after stepping they performed concentric leg exercise at stepwise increasing intensity, while power output was measured. During this concentric exercise and recovery therefrom, phosphorous metabolites were also measured in the m. vastus medialis with magnetic resonance spectroscopy. Creatine kinase and myoglobin in blood were measured before and 72 h after stepping. T1 and T2 1H‐relaxation times for water were calculated from magnetic resonance images collected 72 h after stepping, and used as measures for oedema. The subjects perceived substantial soreness from 24 to 72 h after stepping. The ratio of inorganic phosphate over phosphocreatine at rest increased from 0.12± 0.02 (before) to 0.19± 0.04 (24 h after stepping) (P < 0.05). Creatine kinase activity was slightly elevated 72 h after stepping (71 [49–812] U L‐1 [median, range]; P < 0.05) compared with baseline values (58 [26–409] U L‐1), whereas myoglobin concentration was not significantly elevated (15 [8–120] μg L‐1 compared with 8 [8–41] μg L‐1). In the eccentrically exercised muscles, T1 and T2 values were not or only slightly higher than in the concentrically exercised contralateral muscles. The relation between power and the ratio of inorganic phosphate over phosphocreatine during concentric exercise, and the recovery data for inorganic phosphate, phosphocreatine and pH did not alter after stepping. These data suggest that quadriceps metabolism during concentric exercise and recovery therefrom is not affected by prior eccentric overload, but it cannot be excluded that metabolism will alter during exercise after more strenuous prior eccentric overload.
Characterization of sports by the Vo2 dynamics of athletes in response to sinusoidal work load
Authors: FUKUOKA Y. , GWON O. , SONE R. , IKEGAMI H.
Published: December 2008

The purpose of this study was to evaluate the specificity of maximal oxygen uptake (Vo2max) and the dynamic response of oxygen uptake (Vo2) to sinusoidal work load in distance runners and in American‐football players. Sinusoidal work load during ergometer cycling was carried from 30 W to 60% to Vo2max(60% Vo2max) for a 2 min period. Vo2 was measured by the breath‐by‐breath method. The subjects were 10 distance runners (DRs), 10 American‐football players (AFPs), and 11 untrained men (UTM). Mean Vo2max was 64.4 mL kg‐1 min‐1 in the DRs, 53.1 mL kg‐1 min‐1 in the AFPs and 47.3 mL kg‐1 min‐1 in the UTM. The fundamental amplitudes ofthe Vo2 response, nomalized by dividing by steady state Vo2 at 60% Vo2max were similar in the AFPs (20.3%) and the UTM (19.5%), and both were significantly less than in the DRs (25.5%). Phase shift to work load expressed in degrees was similar in the AFPs (87.7d̀) and UTM (88.0d̀), but significantly greater than in the DRs (80.4d̀). HR dynamics in all three groups were similar to a dynamic Vo2 response. These findings suggest that development of the dynamic Vo2 response and higher Vo2max in the AFPs there is no improvement in the dynamic Vo2 response. The results of the present study demonstrate that athletes participating in different sports have characteristic dynamic Vo2 responses during cycling exercise.
Fat content affects heat capacity: a study in mice
Authors: FABER P. , GARBY L.
Published: December 2008

The specific heat capacity of the human body is a widely used number in calculations related to studies in energy metabolism and temperature regulation. A value of 3.47 kJ kg‐1 K‐1 has been used during the last century, but there have been no direct studies on the dependence of this value on the body fat content. We present here results of measurements of the specific heat capacity of lean and obese mice. The mice were killed and heated to 40.6 d̀C, transferred to a calorimeter and the specific heat capacity was determined from body mass of the mice and temperature rise of water in the calorimeter. We measured the fat fraction of body mass (mt), fat free body mass and water content of the mice and found a marked dependency of the specific heat capacity (Cp) on body fat. In obese mice (fat content 52.76% body wt) the heat capacity was 2.65 kJ kg‐1 K‐1 and in lean mice (fat content 7.55% body wt) the heat capacity was 3.66 kJ kg‐1 K‐1
Vasoactive intestinal peptide regulates angiotensin II catabolism in the rabbit
Authors: DAVIS R. E. , YE V. Z. C. , MACDONALD G. J. , DUGGAN K. A.
Published: December 2008

Although vasoactive intestinal peptide (VIP) is natriuretic it stimulates renin and aldosterone secretion. Therefore, to effect a natriuresis, VIP may need to modulate the sodium conserving actions of the renin angiotensin system (RAS) by another means. One possibility is that it alters the rate of disappearance from the circulation of one or more components of the RAS. We sought to determine whether VIP regulates the rate of catabolism of angiotensin II (Ang II). Steady state metabolic clearance studies of Ang II were undertaken with and without simultaneous VIP infusion. These studies were performed in rabbits on low, normal and high sodium diets, as dietary sodium has been shown to affect the metabolism of both VIP and Ang 11. The effects of VIP on plasma Ang 11 concentration and secretion were also studied. VIP decreased Ang II catabolism in rabbits on low (P < 0.05) and normal sodium diets (P < 0.05). Plasma levels of Ang II increased significantly in response to VIP in rabbits on these diets (low, P < 0.04; normal, P < 0.05). In contrast, in rabbits on a high sodium diet VIP increased the rate of catabolism of Ang II (P < 0.001).

Thus we conclude that the effect of VIP on sodium excretion may be modulated by its effects on Ang II metabolism. The decrease in Ang II catabolism seen in rabbit on low and normal sodium diets may prevent or ameliorate any natriuresis while the more rapid degradation of Ang II which occurs in dietary sodium excess may enhance the natriuretic effect of VIP.
Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium
Authors: RYTVED K. A. , BRODIN B. , NIELSEN R.
Published: December 2008

In the present study we have compared the effects of increased intracellular Ca2+ in whole frog skin and isolated epithelium (Rana temporaria). Cellular Ca2+ was increased by the use of the endoplasmic reticulum Ca2+ ATPase inhibitor, thapsigargin. Serosal addition of thapsigargin to the whole frog skin increased the Na+ transport by increasing the apical Na+ permeability. This could be blocked by the addition of indomethacin or by removal of Ca2+ from the serosal solution. The increase in Na+ transport was accompanied by an increased prostaglandin E2 release. This indicated that the response in Na+ transport was due to a Ca2+ dependent activation of the prostaglandin E2 synthesis. Addition of thapsigargin to isolated epithelia inhibited the Na+ transport and had no effect on the prostaglandin E2 release, though the prostaglandin E2 release from the isolated epithelia could be increased by the addition of arachidonic acid. Addition of prostaglandin E2 increased the cAMP contents of the isolated epithelia significantly, whereas thapsigargin had no significant effect on the cAMP level. Our results demonstrate that serosal addition of thapsigargin causes a release of prostaglandin E2 from the dermis below the transporting epithelium. The prostaglandin E2 diffuses to the epithelium where it activates the Na+ transport by increasing cellular cAMP. The epithelium itself does not contribute significantly to the prostaglandin E2 synthesis. Furthermore an increase in intracellular Ca2+ in the epithelial cells without a concomitant increase in prostaglandin E2 release leads to an inhibition of the active Na+‐transport.
[51Cr]EDTA for measuring total and single nephron glomerular filtration rate in the rat
Authors: LEYSSAC P. P. , CHRISTENSEN P.
Published: December 2008

Clearance and micropuncture experiments were performed in halothane anaesthetized rats. The aim was a comparison of paired estimates of glomerular filtration rate (GFR) from the renal clearance of [51Cr]EDTA (C[51Cr]EDTA) with simultaneous estimates of polyfructosan ((Inutest) CIn),3H,‐ and14C‐labelled inulin clearance (C[3H]Inand C[14C]In, respectively) and proximal tubular fluid/plasma concentration ratios (TF/P) of [15Cr]EDTA and TF/P ratios of14C‐labelled inulin measured in the same samples. C[51Cr]EDTAcorrelated well with, but underestimated CInby ˜ 10%. The correlation coefficient (r) was 0.92. C[51.Cr]EDTAalso correlated with, and underestimated C[14C]Inby 6%,r= 0.88, whereas it overestimated C[3H]Inby 5%, still with a close correlation (r= 0.92). Paired data on proximal (TF/P) ratios of [15Cr]EDTA and [14C]inulin were collected from early, mid and late proximal convolutions. The data were scattered around the line of identity,r= 0.91. It is concluded that [15Cr]EDTA is a valid alternative for estimates of total renal and single nephron GFR in rats and has the advantage of being less expensive than [14C]inulin.
The effects of 2,3‐butanedione monoxime (BDM) on the force‐velocity relation in single muscle fibres of the frog
Authors: SUN Y.‐B. , LOU F. , EDMAN K. A. P.
Published: December 2008

The effects of 2,3‐butanedione monoxime (BDM) on the forcevelocity relaion were studied in single fibres from the anterior tibialis muscle ofRana temporaria(2.2 μm sarcomere length, temperature 1.9‐2.4 d̀C). BDM (1.0 and 1.8 mM) suppressed the maximum tetanic force (Po) and the maximum speed of shortening (Vmax), and increased the main curvature of the force‐velocity relation. The biphasic shape of the forcevelocity curve was maintained well in the presence of BDM, but the interrelation between the two portions of the forcevelocity relation was significantly changed. Caffeine (0.5 mM) added in the presence of BDM increased the initial rate of rise of force during twitch and tetanus, increased the twitch amplitude, but did not affect the maximum tetanic force. The latter finding suggests that the contractile system was fully activated during tetanus in the presence of BDM. The results support the view that BDM affects the cross‐bridge function by exerting a direct action upon the contractile apparatus. The decrease in tetanic force and the change of the force‐velocity relation induced by BDM may be interpreted to show that a larger fraction of the attached cross‐bridges is in a state of low force production under the influence of BDM. This view is further supported by the observation that the instantaneous stiffness of the muscle fibre is reduced proportionally less by BDM than the tetanic force.
Validation of the ‘internal reference technique’ for calibrating microdialysis catheters in situ
Authors: LÖNNROTH P. , STRINDBERG L.
Published: December 2008

In vivo calibration of microdialysis catheters with [3H]glucose as internal reference was done in rat (n= 17) and human (n= 12) subcutaneous tissue. The estimated interstititial glucose level was compared owth the glucose concentration in venous plasma which, in turn, has been shown to be identical to the interstitial glucose concentration. In subcutaneous tissue of anaesthetized male Sprageue‐Dawley rats, interstitial glucose was significantly overestimated (43%, P < 0.005, n= 8, and 19%, P < 0.005, n=9, in nornoglycaemic and hyperglycaemic animals, respectively). Furthermore, fractional outflux of [3H]glucose decreased continuously during prolonged perfusion of the microdialysis catheter. Incontrast, in human subcutaneous tissue microdialysed with two catheters, correct measurements of interstitial glucose could be achieved and the precision was comparableto that obtained with equilibration calibraton in vivo. The average relative error of the mean result of two catheters was 8.9% at a perfusate flow rate of 1 μL min‐1.

It may be suggested that calibration in in vivo of microdialysis catheters with internal references may be used in human subcutaneous tissue. However, it is necessary to validate the calibration technique in each different tissue under reproducible experimental conditions since accumulation of the reference substance in the tissue may create artefactual results.
Cortico‐cortical mediation of short‐latency (lemniscal) sensory input to the motor cortex in deeply pentobitone anaesthetized cats
Authors: ANDERSSON G.
Published: December 2008

In pentobarbitone‐anaesthetized cats, responses were recorded as surface positive potentials in the motor cortex on forelimb and brachium conjunctivum stimulation. In such a preparation, the forelimb nerve responses are mediated via the spino‐cervical tract and the dorsal column‐lemniscal pathway. Lesions of the sensory cortex (sparing only the depth of the coronary sulcus) abolished or reduced short‐latency peripheral responses, in the motor cortex, on both skin and muscle nerve stimulation to less than 10% of control, while brachium conjunctivum responses were unchanged. Lesions of the second somatosensory area alone reduced the motor cortex responses on peripheral nerve stimulation by 10–20%. When the sensory cortex were abolished before the spreading depression reached the recording point, as judged from the brachium conjunctivum response. The depth distribution of positive and negative field potentials, constituting the early componentsof a peripheral response in the motor cortex, closely resembled that of a cortico‐cortical response evoked on stimulation in area 3. It differed from that of thalamo‐cortical response evoked in brachium conjunctivum stimulation. These data suggest that most, if not all, sensory input through the dorsal column and spino‐cervical tract to the motor cortex is mediatd via the sensory cortex.
Plasma atrial natriuretic peptide in Standard bred and Finnhorse trotters during and after exercise
Authors: KOKKONEN U.‐M. , HACKZELL M. , RASANEN L. A.
Published: December 2008

To study the exercise‐induced changes in atrial natriuretic peptide (ANP), a hormone with cardiovascular and renal effects, an incremental submaximal exercise test on a highspeed treadmill was carried out with Standardbred and Finnhorse trotters, the former bred for speed and the latter originally for heavy work. Standardbreds performed the 2 min exercise intervals at speeds of 6, 7, 8, 9 m s‐1and Finnhorses, according to their training status, at 5, 6, 7, 8 m s_1, 4, 5, 6, 7 m s‐1or 5, 6, 7 m s‐1Steady‐state heart rate (HR) was reached within each 2 min interval. The increase in HR was linear and proportional to work intensity and physical condition and it peaked, average 204 beats min‐1, during the last speed of the treadmill. Plasma ANP increased significantly and equally, by 27 + 4 pg mL in both breeds and peaked at 5 min post‐exercise. The rise in ANP during exercise showed good linearity with HR and increasing work intensity. The decrease of ANP after exercise was slow, which may be connected to the regulation of water and electrolytes. Interbreed differences in plasma ANP were not observed. The results suggest a role of ANP in cardiovascular control and fluid balance during and after exercise. In addition to other possible releasing factors during exercise, the increase in HR explains about 40% of the variability in the plasma ANP values.
Effects of age on sarcoplasmic reticulum properties and histochemical composition of fa stand slow‐twitch rat muscles
Authors: DANIELI‐BETTO D. , BETTO R. , MEGIGHIAN A. , MIDRIO M. , SALVIATI G. , LARSSON L.
Published: December 2008

Calcium release activity of sarcoplasmic reticulum and enzyme‐histochemical properties were investigated in extensor digitorum longus (e.d.l.) and soleus muscles in young (4 months) and old (24 months) male rats. With age, the caffeine threshold concentration for calcium release from the sarcoplasmic reticulum of soleus skinned muscle fibres showed only minor modifications. On the other hand, in e.d.l. skinned muscle fibres, the caffeine threshold concentration decreased significantly (P < 0.05). The histochemical fibre type composition changed with age both in soleus and in e.d.l. muscles, showing a common transformation toward a more oxidative histochemical profile. In fact, in aged soleus, a significant (P < 0.05) increase was observed of type 1 fibres to represent almost the totality of the muscle fibres (more than 98%), while types 2C and 2A were reduced in proportion. In aged e.d.l. the percentage of type 1 (P < 0.05), 2A and 2X (a recently identified fourth component of the fast‐twitch muscle types) fibres increased, with a reduction of type 2B (P < 0.01) fibres. The present results suggest that the changes in contractile properties of aged muscles may be related to the changes not only in fibre composition but also in the mechanism of calcium release from sarcoplasmic reticulum.
Strain difference in early postnatal sleep‐wake behaviour between Alko Alcohol and Wistar rats
Authors: HILAKIVI I. , TAIRA T.
Published: December 2008

Early postnatal sleep‐wake behaviour of male and female rats of Alko Alcohol and Wistar strain was studied using a static charge sensitive mattress when the rats were aged 1 and 2 weeks postnatally. In both strains and sexes, waking time relative to total recording time increased, proportion of quiet state did not change, and that of active sleep decreased during the second postnatal week. The number of long active sleep stages relative to short active sleep stages and the duration of sleep‐wake stages increased with age. Transitions between quiet state and active sleep became fewer with increasing age. Waking time increased more in Wistar rats than in Alko Alcohol rats. At 1–2 weeks of age, the percentage of active sleep and the number of long active sleep stages relative to short active sleep stages were larger, and the duration of sleep‐wake stages longer in Alko Alcohol than in Wistar rats. Sleep‐wake behaviour did not differ between the sexes of either strain or age. Selective breeding for high alcohol preference in Alko Alcohol rats may have caused a genetic trait in early postnatal sleep‐wake behaviour.
Pronounced and rapid plasma volume reduction upon quiet standing as revealed by a novel approach to the determination of the intravascular volume change
Authors: LUNDVALL J. , BJERKHOEL P.
Published: December 2008

Plasma volume (PV) changes to 15 min quiet standing were analysed (Hb/Hct‐alterations) in two studies (nine and 11 healthy males). Data confirmed and extended our findings that blood, arterial or venous, sampled on standing fails to reveal the induced overall haemoconcentration (PV loss). First, standing led to markedly incomplete mixing of blood between circulatory compartments. Secondly, with sampling of antecubital venous blood, haemoconcentration was strongly affected by regional plasma loss and, apparently equally important, by regional blood flow. These difficulties were circumvented, however, by the finding that the PV restitution (haemoconcentration) in the recumbent subject after standing fitted invariably a monoexponential function with striking precision. It allowed, by extrapolation, a seemingly superior definition of the PV reduction at the very end of standing as supported by the fact that PV changes from Hb/Hct and from IgM protein concentration changes were similar, refuting that Fcell‐changes contributed to the pronounced Hb/Hct changes. The described novel approach revealed a nicely reproducible PV loss of no less than 692 ± 46 mL (18.1 ±0.6%, Study I; 18.4 ± 0.5%, Study II), or ± 11% reduction of blood volume, showing that quiet standing leads to a much more rapid and haemodynamically important decrease in PV than reported previously. Yet, PV was virtually restored within 20 min of recumbency after standing, with 50% recovery within 6 min and regain of as much as 70 mL in the very first min. The latter data indicate that the body possesses a surprising capacity for rapid fluid transfer from the extra‐ to the intravascular space.