bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies of muscarinic receptor reserve linked to phosphoinositide hydrolysis in parotid gland and cerebral cortex
Authors: EK B. , ANTONSSON B.‐M.
Published: December 2008

Hydrolysis of inositol phospholipids caused by muscarinic agonists was studied in the guinea‐pig parotid gland (PG) and cerebral cortex (CX). The present study describes the effect of two muscarinic agonists, carbachol and oxotremorine, on stimulation of phosphoinositide hydrolysis and on binding of [3H]NMS in the presence of the irreversible muscarinic antagonist benzilyl choline mustard (BCM).

Carbachol and oxotremorine stimulated the formation of inositol phosphates in PG, pD2(Carb) = 5.3 ± 0.1, pD2(Oxo) = 5.9 ± 0.1 and in CX, pD2(Carb) = 4.3 ± 0.2, pD2(Oxo) = 5.8 ± 0.2. In the present study slices from both tissues have been exposed to 0.1 μM BCM for 2, 5 and 10 min. Treatment for 10 min caused a 75–85%, reduction in specific [3H]N‐methyl scopolamine ([3H]NMS) binding sites in both PG and CX. Following 2 min BCM treatment of PG a marked decrease in pD2value of the carbachol‐stimulated inositol phosphate formation was found. This effect was not found in CX. The results showed that a 30–40% reduction in binding sites shifted the carbachol concentration response curve to the right by one order of magnitude and reduced the oxotremorine‐induced release of inositol phosphates by approximately 20%. In PG, the BCM‐induced reduction of the carbachol‐stimulated inositol phosphate formation was paralleled by the reduction in receptor binding sites. Similar treatment, but in CX, showed a lower reduction of the carbachol‐stimulated inositol phosphate formation as compared to the reduction in receptor‐binding sites.

The results from the present study indicate that stimulation of phosphoinositide hydrolysis in PG involves a receptor reserve, mainly via stimulation of M2‐muscarinic receptors.
The cytosolic chloride concentration in macula densa and cortical thick ascending limb cells
Authors: SALOMONSSON M. , GONZALEZ E. , KORNFELD M. , PERSSON A. E.G.
Published: December 2008

It is believed that chloride transport through the macula densa (MD) cells is a factor involved in the tubuloglomerular feedback (TGF) mechanism and in MD‐mediated renin release. In this study isolated and perfused rabbit kidney cortical thick ascending limb (cTAL) segments containing MD plaques and attached glomeruli were loaded with chloride (CL‐sensitive) 6 methoxy‐l‐fluorophore (sulphanate‐propyl) quinolinium (SPQ). MD and cTAL intracellular chloride concentration ([Cl‐]i) was determined by using image‐intensified video microscopy and digital image‐processing for measuring the intensity of the emitted SPQfluorescence. With 150 mM NaCl in lumen and bath the [Cl‐], in MD and cTAL cells was 58.8 ± 7.2 mm (n= 20) and 68.7 ± 9.8 mm (n= 14), respectively. When the presumed luminal Na+‐2Cl‐‐K+ co‐transporter was blocked by adding 10‐‐4m furosemide, the [Cl‐]i was reduced in both, MD and cTAL cells from 55.5 ± 11.9 to 28.6 ± 10.0mm (n= 10) and from 43.8± 2.6 to 13.1± 4.5mm (n= 5), respectively. A reduction in luminal NaCl from 150 to 30 mm also decreased both, MD and cTAL [Cl‐]i from 69.4± 9.1 to 36.5± 5.1 mm (n= 9) and from 82.9 ±14.5 to 49.4± 8.0 mm (n= 8), respectively. Basolateral addition of the Cl‐‐channel blocker NPPB increased MD [Cl‐], from 31.1± 2.0 to 100.7± 17.0 mm (n= 5) and cTAL [Cl‐]i from 44.4 ± 12.9 to 89.7 ± 11.7 mm (n= 5). These results show the existence of a luminal Na+‐2C1‐K+ cotransporter and a basolateral Cl‐ conductance, and that chloride transport is directed from the luminal to the basolateral side during symmetrical conditions. They also indicate that sensing of luminal NaCl by the MD cells could be of importance in the TGF mechanism and MD mediated renin release.
The ability of ruthenium red to reduce the autonomic reflexes and peptide release evoked by capsaicin administration in the pig in vivo
Authors: ALVING K. , FRANCO‐CERECEDA A.
Published: December 2008

In the present study we have investigated the cardiovascular effects and peptide‐releasing actions of different capsaicin doses in the absence and presence of the inhibitor of Ca2+ fluxes, ruthenium red, in the pig in vivo. Bolus injections of capsaicin (10, 100 and 1000μg kg‐1 i.v.) evoked a concentration‐dependent increase in mean arterial pressure and heart rate (HR), while in the bronchial and nasal circulations, a fall in vascular resistance was observed. At the highest capsaicin dose used, there was, in addition, a marked increase in arterial levels of calcitonin gene‐related peptide (CGRP)‐and neuropeptide Y (NPY)‐like immunoreactivity (LI). Ruthenium red (RR) significantly reduced the CGRP‐LI release, but not the outflow of NPY‐LI, at the highest dose of capsaicin as well as the functional effects evoked by low dose capsaicin administration. The inhibitory effects of RR were reversible, i.e. 30 min after ruthenium red administration, bolus injections of capsaicin (10 and 100 μg kg‐1) induced responses similar to those seen in controls.

It is concluded that capsaicin given intravenously to the pig produces profound haemodynamic effects and release of CGRP‐ and NPY‐LI through direct activation of a population of C‐fibre endings and increased autonomic discharge. RR inhibits not only the local peptide‐releasing properties of capsaicin, but also the centrally directed discharge activity leading to reflex responses, with the latter being less sensitive to RR.
Age‐related changes in force and efficiency in rat skeletal muscle
Authors: De HAAN A. , De RUITER C. J. , LIND A. , SARGEANT A. J.
Published: December 2008

We investigated the effect of age on (the reduction of) work output, efficiency and muscle fibre type composition. Rat medial gastrocnemius muscles of three age‐groups performed a series of 15 repeated contractions within 6 s (blood flow was arrested). Stimulation and shortening velocities were chosen as optimal for each group, while all muscles shortened over the same relative fibre lengths. The fibre type composition showed a higher proportion of the oxidative type IIBd fibres in the middle‐aged group [5 months old; 39.8 ± 6.8 vs. 23.6 ± 4.2% of the fibre area in the young rats (1.3 months old)] in contrast to the type IIBm fibres (52.9 vs. 67.9%, respectively), while the old group (22 months old) was not different from the middle‐aged group. Work output in the last contraction (relative to the first contraction) was not different between the age‐groups (53.1 ± 18.1; 48.± 6.5 and 61.1± 6.2%, respectively). High‐energy phosphate utilization was not different between the groups (150.6 ± 11.2; 154.6 ± 15.6 and 157.2 ± 7.0 μmol g‐1dry wt, respectively). However, the efficiency was 30% lower in the muscles of the youngest group, which corresponds with a lower specific power and specific tension. Since the change in fibre type composition is unlikely to be the cause of the low efficiency in the young animals, the causes remain unclear, but may be related to the rapid growth of the young rats in our study.
Enzymes of glutathione synthesis in dog skeletal muscles and their response to training
Authors: MARIN E. , KRETZSCHMAR M. , AROKOSKI J. , HÄNNINEN O. , KLINGER W.
Published: December 2008

The glutathione synthesizing enzymes, γ‐glutamyl cysteinyl synthetase and glutathione synthetase, were found in all skeletal muscles studied in dogs. Both occurred also in the liver, but only the former in the lung. The influence of physical training on these enzyme activities was also investigated. For 30 weeks the dogs ran 5 days week‐1on a treadmill at a 15° uphill grade. A 1.5– to 2–fold increase in the y‐glutamyl cysteinyl synthetase and 3–fold increase in the glutathione synthetase activities was observed in muscles affected by the training procedure (m. triceps, m. extensor carpi radialis and m. gastrocnemius). No training effect could be observed in the splenius and longissimus dorsi muscles or in the liver. The training increased total glutathione levels in the lung and gastrocnemius muscle as well as in the plasma. Glutathione disulfide levels were not altered. Acute physical exercise significantly decreased the plasma total glutathione concentrations in the trained dogs. The results indicate a training responsive adaptation of glutathione system in skeletal muscle.
Sympathetic baroreflex control of vascular resistance in comfortably warm man. Analyses of neurogenic constrictor responses in the resting forearm and in its separate skeletal muscle and skin tissue compartments
Authors: EDFELDT H. , LUNDVALL J.
Published: December 2008

Resting forearm vascular resistance changes elicited in male volunteers by graded reflex sympathetic activation evoked by graded lower body negative pressure (LBNP) were studied at room temperatures of 24–25 and 2C–21 7deg;C. The latter condition caused strong suppression of skin flow and permitted preferential analysis of muscle responses and, by comparison with responses at 24–25 7deg;C, secondary estimation of circulatory reactions in the skin. Short‐lasting LBNP‐bouts (1.5 min) allowed analyses of reflex vascular reactions to high and barely tolerated LBNP (85 mmHg) and thereby to high levels of circulatory stress and sympathetic nerve discharge, yet without risks for the subjects under study. Both muscle and skin reacted intensely and in agradedmanner to graded sympathetic activation with very pronounced resistance change (74–77% flow decline; 350–400% resistance rise above control level) at high LBNP. Therefore, the sympathetic vasomotor fibres can exert a very potent control of vascular resistance both in skeletal muscle and in skin under thermoneutral conditions, and both tissues apparently can serve as major targets for powerful sympathetic homeostatic baroreflexes. Evidence indicated that this control is exerted from both low‐pressure cardiopulmonary and high‐pressure arterial baroreceptor areas. These conclusions deviate from previous literature, in which baroreflex sympathetic vasoconstriction in the human limb has been proposed to be more or less selectively mediated from cardiopulmonary receptors and, further, muscle to respond fully already at mild circulatory stress without further constriction if the stimulus is increased.
Dopaminergic influence on the excitability of antidromically activated Renshaw cells in the lumbar spinal cord of the rat
Authors: MAITRA K. K. , SETH P. , THEWISSEN M. , ROSS H.‐G. , GANGULY D. K.
Published: December 2008

The interaction between dopaminergic and cholinergic systems in the mammalian central nervous system, which is thought to have important implications in the pathophysiology of major extrapyramidal disorders, has never been adequately demonstratedin vivo. Renshaw cell burst responses to single electrical shocks to lumbar ventral roots in spinalized and decerebrated rats were studied. In this monosynaptic cholinergic pathway, apomorphine, a dopaminergic receptor agonist, inhibited whereas the D2‐antagonist sulpiride facilitated the burst responses. The mutual antagonism of the two drugs and the depression coupled with the faster decay of post‐tetanic potentiation of Renshaw cells by apomorphine demonstrate the involvement of presynaptic D2‐receptors through which dopamine can modulate acetylcholine‐mediated central synaptic transmissionin vivo. The study also provides further evidence for the involvement of the spinal cord in extrapyramidal disorders.
Membrane potential oscillations and corticothalamic connectivity in rat associational thalamic neurons in vitro
Authors: HU B.
Published: December 2008

Thalamic relay neurons were recorded from the dorsolateral and lateroposterior nuclei of the rat thalamus in a superfused explant preparation. The mean membrane potential of these cells was –67 ± 7 mV, input resistance 114 ± 31 MΩ and spike amplitude 75 ± 6 mV. Low‐threshold slow membrane potential oscillations (1–4 Hz) were present in about 46% of the neurons. They occurred either spontaneously or following a membrane potential perturbation. In a subpopulation of cells, we also observed a high‐threshold membrane oscillation when cells were depolarized above –45 mV. This oscillation consisted of bursts of low‐amplitude spikes interrupted by rhythmic afterhyperpolarizations. Stimulation of the corticothalamic pathway elicited prolonged inhibitory postsynaptic potentials in associational thalamic neurons. In the presence of picrotoxin, corticothalamic input evoked prominent excitatory postsynaptic responses that showed marked short‐term synaptic plasticity. Our results suggest that associational thalamic neurons maintained in vitro have a strong tendency to exhibit membrane oscillations. In addition, they receive a direct excitatory cortical input that remained functional in explant preparation.
On the usefulness of Fura‐2 measurements of intrasynaptosomal calcium levels in rat cortical synaptosomes to study mechanisms of presynaptic function
Authors: HU P.‐S.
Published: December 2008

Levels of [Ca2+]iin rat cortex synaptosomes were measured using the Ca2+indicator Fura‐2. Ca2+influx was induced by veratridine in a concentration‐dependent manner (1–10μm). The resulting increase in [Ca2+]iwas inhibited by tetrodotoxin (TTX). K+(18 mm) increased the [Ca2+]iwhich was not influenced by TTX. K+‐channel blockers such as 4‐aminopyridine,α‐andδ‐dendrotoxinper sewere ineffective. The veratridineinduced Ca2+influx in synaptosomes was reduced by L‐type Ca2+‐channel blockers, such as felodipine, nifedipine and PN‐200‐110, verapamil and diltiazem.ω‐Conotoxin, an N‐type Ca2+‐channel blocker, did not inhibit the veratridine‐stimulated [Ca2+]iincrease. Bay K 8644, an L‐channel agonist, stimulated an increase of [Ca2+]iin synaptosomes which was not sensitive to TTX.

R‐N6‐Phenyl‐isopropyl‐adenosine (R‐PIA) and clonidine, agonists at adenosine A1‐receptors and α2‐adrenoceptors, respectively, did not influence the veratridinestimulated [Ca2+]iincrease. R‐PIA did not interact with Bay K 8644‐stimulated [Ca2+]iincrease in synaptosomes.

The results for all the substances used show major differences between the effects on Ca2+influx in synaptosomes and on the electrically evoked neurotransmitter release in slice preparations. Thus, the synaptosome preparation is not a generally applicable experimental model for the study of Ca2+mechanisms of presynaptic neuromodulation.
An indifference point for electrical impedance in humans
Authors: PERKO G. , PAYNE G. , SECHER N. H.
Published: December 2008

Regional electrical impedance was used over eight sections of the human body (two thoracic; one abdominal; two thigh; two around the knee; and one lower leg) to determine the volume indifference point during passive head‐up tilt in eight subjects. Head‐up tilt was performed in 10± increments from 0± to 60± over 6 min. Electrical impedance increased over the thorax in proportion to the head‐up tilt angle, while abdominal impedance did not change significantly, and over the thigh and the lower leg it decreased with increasing head‐up tilt angle. No change in electrical impedance was noted just above the knee, and electrical impedance just below the knee decreased only marginally. Results demonstrate minimal fluid accumulation around the knee during head‐up tilt. Furthermore, in humans the electrical impedance and therefore probably the volume indifference point is positioned between the umbilicus and crista iliaca.
Inhibitory effect of endothelin on renin release in dog kidneys
Authors: NAESS P. A. , CHRISTENSEN G. , KIIL F.
Published: December 2008

To investigate the effect of endothelin on renin release, experiments were performed in barbiturate‐anaesthetized dogs with denervated kidneys. Intrarenal infusion of endothelin (1 ng min‐1kg‐1body wt) reduced renal blood flow (RBF) from 145 ± 10 ml min‐1to 98 ± 9 ml min‐1without altering renin release (1 ± 1μg angiotensin I (AI) min‐1). Renin release was then increased either by renal arterial constriction or ureteral occlusion. When renal arterial pressure was reduced to 50 mmHg, renin release averaged 79 ± 20μg AI min‐1in six dogs and fell significantly to 24 ± 6μg AI min‐1during endothelin infusion. During ureteral occlusion the inhibitory effect of endothelin on renin release either during inhibition ofβ‐adrenergic activity with propranolol or after inhibiting prostaglandin synthesis by indomethacin during intrarenal infusion of isoproterenol was examined. After propranolol administration ureteral occlusion increased renin release from 5 ± 2μg AI min‐1to 38 ± 12μg AI min‐1in six dogs. Subsequent intrarenal endothelin infusion (1 ng min‐1kg‐1body wt) during maintained ureteral occlusion reduced renin release to 10 ± 3μg AI min‐1. In six other dogs prostaglandin synthesis was inhibited by indomethacin. Subsequent infusion of isoproterenol (0.2μg min‐1kg‐1body wt) to stimulateβ‐adrenoceptor activity increased renin release from 13 ± 4μg AI min‐1to 68 ± 8μg AI min‐1during ureteral occlusion. Intrarenal endothelin infusion (1 ng min‐1kg‐1body wt) reduced renin release to 22 ± 3μg AI min‐1during continuous isoproterenol infusion and ureteral occlusion. Hence endothelin inhibits renin release induced by renal arterial constriction or ureteral occlusion. Similar inhibitory effects whether renin release was raised by increasing prostaglandin synthesis or by stimulatingβ‐adrenergic activity suggest a direct effect of endothelin on the juxtaglomerular cells.
Effect on renin release of inhibiting renal nitric oxide synthesis in anaesthetized dogs
Authors: NAESS P. A. , CHRISTENSEN G. , KIRKEBØEN K. A. , KIIL F.
Published: December 2008

Nitric oxide plays an important role in the regulation of basal renal blood flow. This study was performed to examine whether selective inhibiti± of renal nitric oxide synthesis affects renin releasein vivo. Accordingly, in six barbiturate‐anaesthetized dogs renin release was examined before and after intrarenal infusion of the selective inhibitor of nitric oxide synthesis, NG‐nitro‐l‐arginine (NOARG). NOARG was infused into the renal artery to yield a renal arterial blood concentration of 0.4μmol ml‐1. NOARG did not change systemic arterial blood pressure and glomerular filtration rate, but reduced basal renal blood flow by 26 ± 2%. Urine flow, sodium and potassium excretion were reduced after inhibition of renal nitric oxide synthesis. Basal renin release (3 ± 2μg AI min‐1) was not altered by NOARG infusion (1 ± 1μg AI min‐1). To stimulate renin release the renal artery was constricted to a renal perfusion pressure of 50 mmHg. At this perfusion pressure infusion of NOARG reduced renin release significantly from 48 ± 11μg AI min‐1to 14 ± 4μg AI min‐1. In conclusion, inhibition of renal nitric oxide synthesis reduces basal renal blood flow and reduces renin release stimulated by renal arterial constriction. These findings indicate that renal nitric oxide modulates both renal blood flow and renin releasein vivo.
Rhythmic contractions of isolated small arteries from rat: influence of the endothelium
Authors: GUSTAFSSON H. , MULVANY M. J. , NILSSON H.
Published: December 2008

Small arteries of the mesenteric arcade from Wistar rats display rhythmic oscillations superimposed on the tonic contractile response when exposed to submaximal doses of noradrenaline. We have previously shown that mechanical removal of the endothelium abolishes these oscillations. In the present study different methods to eliminate or modify the influence of the endothelium were used in order to further characterize the mechanisms behind rhythmic contractions in these vessels.

Endothelium was removed either mechanically or chemically by perfusing the vessels with 0.3% CHAPS. The absence of functional endothelium enhanced noradrenaline sensitivity and simultaneously abolished oscillations in tension and membrane potential, but did not affect resting membrane potential. The rhythmic activity was also reduced or abolished by exposure to haemoglobin, methylene blue, LY83583 orl‐NNA. Indomethacin and propranolol were without effect. Sodium nitroprusside or the permeant analogue of cyclic GMP, 8‐bromo cyclic GMP, restored rhythmic activity in precontracted endothelium‐denuded vessels. The data suggest that release of nitric oxide from the endothelium, and subsequent generation of cyclic GMP in the smooth muscle, activates oscillations in membrane potential and tension; the oscillator itself appears to be located within the smooth muscle cells.
Vascular effects of endothelin‐1 in the cat; modification by indomethacin andl‐NAME
Authors: GRANSTAM E. , WANG L. , BILL A.
Published: December 2008

Intravenous infusion of endothelin‐1 (ET‐1) in the cat, 60 pmol × kg body wt‐1x min‐1for 5 min, induced an increase in mean arterial blood pressure (MAP) of 41.3 ± 4.8 mmHg (n= 6;P< 0.001). Blood flow, as determined with radioactive microspheres, was reduced in many tissues. Reductions by 70–80% were observed in the choroid plexus, pineal and pituitary glands. Total cerebral blood flow was reduced by 18–23%. Pre‐treatment with indomethacin or a combination of indomethacin andl‐NAME caused vasoconstriction in many tissues and modified the responses to ET‐1 in a variable way, suggesting that normally, ET‐1 tends to release arachidonic acid metabolites and nitric oxide with great variations between different tissues.

Intracerebroventricular infusion (i.c.v.) of ET‐1, 10 pmol × kg body wt‐1x min‐1, caused an increase in MAP of 79 ± 11 mmHg (n= 6;P< 0.001). Regional blood flow in the medulla oblongata, medulla spinalis, choroid plexus, pineal and pituitary glands was reduced by 60–80%. Heart rate, cardiac output and coronary blood flow were significantly increased after 30 min i.c.v. infusion, indicating an activation of the heart, most probably as part of a central ischaemic response.

Our results indicate that in many tissues the vasoconstrictive effect of ET‐1 is influenced by indomethacin‐ andl‐NAME‐sensitive vasodilator mechanisms that are activated by the peptide. In the CNS, there may be marked effects on regional blood flow after i.c.v. infusion.
Muscle strength and serum testosterone, cortisol and SHBG concentrations in middle‐aged and elderly men and women
Authors: HÄKKINEN K. , PAKARINEN A.
Published: December 2008

Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44–57; n= 9), F50 years (range 43–54; n= 9), M70 years (range 64–73; n= 11) and F70 years (range 63–73; n= 11) volunteered as subjects for examination of muscle cross‐sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle‐aged groups. Maximal force of 2854 ± 452 N in M50 was greater (P < 0.05) than that of 2627 ± 752 N recorded for F50 as well as the force of 2787 ± 843 in M70 was greater (P < 0.001) than that of 1849 ± 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.001) than in F70. Both middle‐aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle‐aged subjects (r= 0.66; P < 0.01) and in the elderly subjects (r= 0.69; P < 0.01). The mean concentration of serum testosterone in M50 was slightly (n.s.) greater than in M70 and in F50 significantly (P < 0.05) greater than in F70. Serum SHBG levels were lower in the males (P < 0.01) than in the females and serum testosterone/SHBG ratio in M70 and in F70 were lower (P < 0.05) than in M50 and in F50, respectively. In the females significant positive correlations were observed between the individual values in serum testosterone concentration and the values both in the CSA (r= 0.46; P < 0.05) and in maximal force (r= 0.62; P < 0.01) as well as between serum testosterone/SHBG ratio and both the CSA (r= 0.55; P < 0.05) and maximal force (r= 0.68; P < 0.01). The present results imply that the decreasing basal level of blood testosterone over the years in aging people, especially in females, may lead to decreasing anabolic effects on muscles thus having an association with age‐related declines in the maximal voluntary neuromuscular performance capacity in aging people.
In‐vivoeffects of endothelin‐1 and ETareceptor blockade on arterial, venous and capillary functions in skeletal muscle
Authors: Ekelund U. , Albert U. , Edvinsson L. , Mellander S.
Published: December 2008

Results fromin vitrostudies have indicated that endothelin‐1 is a main candidate for endothelium‐derived contracting factors. The aim of thisin vivostudy was to describe in quantitative terms the effects of endothelin‐1 (ET‐1), and of ETareceptor blockade, on vascular tone (resistance) in large‐bore arterial resistance vessels (> 25 μm), small arterioles (< 25 μm) and the veins, as well as on capillary pressure and fluid exchange in cat gastrocnemius muscle. Endothelin‐1 (100–1600 ng kg‐1 min‐1, i.a.) elicited, after an initial transient dilation, a strong dose‐dependent constrictor response in all three consecutive vascular sections, yet with a preferential action on the small arterioles and the veins. The vasoconstriction developed very slowly over about 1 h and was also long‐lasting after cessation of the infusion. Our main quantitative analysis refers to effects elicited by 20 min long i.a. infusions of ET‐1 at a dose of 400 ng kg‐1 min‐1. At the end of this period, the peptide caused, on average, a three‐fold increase in total regional vascular resistance, in turn explained by a 70% increase in large‐bore arterial resistance, a 280% increase in arteriolar resistance and a 220% increase in venous resistance. The latter effect was also manifested as a pronounced capacitance response, and as a decrease in the pre‐ to post‐capillary resistance ratio leading regularly to a rise in capillary pressure, net transcapillary fluid filtration and oedema formation which is unusual for a vasoconstrictor. The new specific competitive ETAreceptor antagonist FR 139317 was found to be fully effectivein vivo, insofar as it abolished the constrictor response to endothelin‐1. ETAreceptor blockade, or administration of phosphoramidon, an inhibitor of ET‐1 production, did not influence the level of basal vascular tone, indicating no significant endogenous release of ET‐1 under resting conditions. This contrasts to the established pronounced endogenous release of endothelium‐derived nitric oxide. Finally, vascular myogenic regulation was found not to be mediated by ET‐1. The results, taken together, suggest a possible role of ET‐1 in long‐term, rather than short‐term, regulation of vascular tonein vivo, perhaps especially during pathophysiological conditions.
Endothelium determines stabilization of the pressure drop in arteries
Authors: KHAYUTIN V. M. , NIKOLSKY V. P. , ROGOZA A. N. , LUKOSHKOVA E. V.
Published: December 2008

To ascertain whether the relative invariance of the pressure drop along the arterial cascade—from the aortic arch down to include the saphenous artery—during increases of saphenous outflow (Khayutin et al. 1993), is determined mainly by dilation of the latter, and to discover whether this invariability is a manifestation of endothelium‐mediated vasodilation, the pressure drop along the rat saphenous artery was measured in situ during exposure of the artery to rectangular pulses or slow ramps of blood flow. At flow rates below a critical value of about 0.3 ml min‐1, flow increase was followed by a proportional increase of pressure drop. In contrast, with further flow increase, up to the values five to six times beyond the critical one, the steady state pressure drop did not increase at all, or only to a minor extent. This ‘pressure drop stabilization’ was shown to be unrelated to the decline of distending pressure, but to result from a true artery dilation commensurate with the flow increase. Interference with the endothelium by way of 90 mm hydrogen peroxide eliminated the stabilization effect, whereas noradrenaline‐induced constrictions could be increased about three‐fold. The ‘threshold’ shear stress on the endothelium, needed to initiate saphenous artery dilation, was estimated to be 74±4 dyn cm‐2. The functional importance of stabilizing the pressure drop along the arterial conductance and resistance vessels is discussed.
Intense slow hypoxic pulmonary vasoconstriction in gas‐filled and liquid‐filled lungs: an in vivo study in the rabbit*
Authors: VEJLSTRUP N. G. , DORRINGTON K. L.
Published: December 2008

To examine the hypothesis that hypoxic pulmonary vasoconstriction may have a slower time course and greater intensity than is currently recognized, experiments were conducted in twelve anaesthetized rabbits subjected to unilateral lung hypoxia for 6 h. Endobronchial cannulation was used to maintain apnoea of one lung at constant airway pressure whilst inflating the lung with nitrogen or liquid. The second lung was ventilated with oxygen to maintain normocapnia and oxygen transfer. A pulmonary artery catheter was introduced non‐invasively. Pulmonary shunt was derived from mixed venous and arterial blood gas parameters. Pulmonary artery pressure was monitored continuously and cardiac output was estimated from oxygen uptake measurements before and after 6 h unilateral hypoxia. The experiments show that a rapid phase of hypoxic pulmonary vasoconstriction is followed by a slow phase which develops over hours. The slow phase is associated with a massive blood flow diversion from the hypoxic lung, such that pulmonary shunt after 6 h unilateral hypoxia is indistinguishable from baseline shunt during bilateral ventilation with oxygen. The response is reversible, but with a similarly slow time course. Results from nitrogen and liquid filling of the lung are similar. These findings are consistent with early experiments by Dirken and Heemstra in 1948 (Quart J Exp Physiol 34, 193–211), and challenge the prevailing notion that hypoxic pulmonary vasoconstriction is always a rapid and relatively weak physiological response to hypoxia.
The shivering response during cross‐circulation in the common eider duck (Somateria mollissima)
Authors: MERCER J. B. , HAMMEL H. T.
Published: December 2008

The possible role of humoral factors in the control of shivering in the common eider duck (Somateria mollissima) was investigated using a cross‐circulation technique. Pairs of animals were coupled so that the arterial system of one animal was connected to the venous system of the other. The rate of blood transferral was 12.8 ml min‐1. By adequate heparinization of the extracorporeal blood supply, cross‐circulation could be maintained for periods of up to 12 h. The temperature of blood entering each animal (Tinlet) was controlled by heat exchangers. During control experiments Tinlet was maintained at a temperature close to normal body temperature. During cooling experiments Tinlet was maintained at c. 20 °C. Changes in metabolic heat production and oesophageal temperature in response to blood cooling were measured in cross‐circulated pairs of animals cooled simultaneously or individually. Based on analysis of the metabolic responses under the different experimental situations, no evidence was found to indicate that blood‐borne substances are involved in the shivering response in these animals.
A comparative study on the synthesis of dopamine in the human, dog and rat kidney
Authors: SOARES‐DA‐SILVA P. , FERNANDES M. H. , PESTANA M.
Published: December 2008

The present work has examined the ability of human, canine and rat renal tissues to synthesize dopamine from added L‐3,4‐dihydroxyphenylalanine (l‐DOPA); the deamination of newly‐formed dopamine into 3,4‐dihydroxyphenylacetic acid (DOPAC) was also studied. In some experiments, slices of renal cortex obtained from the human, dog and rat kidneys were used; tissues were incubated with increasing concentrations (5–5000 μM) ofl‐DOPA. The accumulation of newly‐formed dopamine was, in all three species, found to be dependent on the concentration ofl‐DOPA, being the rat renal tissues endowed with a greater ability to produce dopamine, followed by the human and the dog tissues. In experiments performed in kidney homogenates, the decarboxylation ofl‐DOPA into dopamine was also found to be dependent, in all three species, on the concentration ofl‐DOPA used (10–5000 μm). AAAD activity as determined in kidney homogenates was found to be in the rat kidney (Vmax= 7.7±0.8 nmol mg‐1protein h‐1) higher than that occurring in the human (Vmax= 5.8±0.6 nmol mg‐1protein h‐1) and the dog kidney (Vmax= 3.9 ± 0.5 nmol mg‐1protein h‐1). No statistically significant differences were found between theKmvalues of the three species (human, 62±8 μM; dog, 54±6 μM; rat, 82±12 μM). A considerable amount of newly‐formed dopamine in both kidney slices and homogenates was converted into DOPAC; the DOPAC /dopamine ratios in these experimental conditions were greater in the human kidney, followed by the rat and dog. It is concluded that the decarboxylation ofl‐DOPA into dopamine is greater in the rat kidney followed by the human and dog, whereas the deamination of the amine into DOPAC appears to be greater in human renal tissues.
On the involvement of tachykinin neurons in the secretory nervous reflex elicited by cholera toxin in the small intestine
Authors: SJÖQVIST A. , BRUNSSON I. , THEODORSON E. , BRODIN E. , JODAL M. , LUNDGREN O.
Published: December 2008

The possible involvement of tachykinins in the nervous reflex activated by exposing the intestinal mucosa to cholera toxin was investigated in cats and rats. Three types of experiments were performed. In cats the release of tachykinins into blood was followed after placing cholera toxin in the intestinal lumen. In rat experiments a tachykinin receptor antagonist (Spantide II) was given close i.a. and its effect on cholera toxin‐evoked fluid secretion was studied. Finally, in rats the effect of cholera toxin on the SP contents in the intestinal mucosa was studied. No release of tachykinins could be demonstrated. Spantide II did not change the rate of cholera toxin induced secretion. The SP content in the intestinal mucosa was not influenced by placing the toxin in the intestinal lumen. Hence, no experimental evidence was obtained for the involvement of a tachykinin neuron in the intestinal secretory nervous reflex activated by cholera toxin. Based on observations reported in the literature the involvement of an acetylcholine/tachykinin neuron in the reflex is tentatively discussed.
Transcellular fluid secretion induced by cholera toxin and vasoactive intestinal polypeptide in the small intestine of the rat
Authors: SJÖQVIST A. , FIHN B.‐M.
Published: December 2008

The permeation of intravenously administered 51Cr‐EDTA and [14C]mannitol to the perfused intestinal lumen was measured in anaesthetized rats together with the net intestinal fluid. Net fluid secretion was induced by cholera toxin or by intravenous infusion of vasoactive intestinal polypeptide (VIP). The plasma clearance of Cr‐EDTA and mannitol was 0.9 ± 0.1 and 1.4 ± 0.2 μl min‐1 g‐1 intestine during the control period prior to the secretion and the net fluid absorption was about 7 ± 5 μl min‐1 g‐1. Cholera toxin induced a net fluid secretion of about 30 ± 7 μl min‐1 g‐1 but the clearance did not rise but decreased significantly. The findings for VIP‐induced secretion were similar. No indication of solvent drag was seen. Thus it is concluded that the fluid was secreted in channels which were smaller than the probes and we propose that the secreted fluid entered the intestinal lumen through the epithelial cells and not by the paracellular route. The decreased permeation of Cr‐EDTA and mannitol from plasma to lumen during volume secretion suggest that there was a decreased mucosal permeability during the secretion. The decrease in permeability was consistent with a decrease in pore size. One explanation of the data is that the pore radius contracted from about 35 to 15 Å during cholera if we assume a homogenous pore population. However, the data indicated that there was not a uniform size of the pore. A more plausible alternative is the presence of a small number of large pores (100 Å or more) which could decrease in size while the majority of pores had a constant radius of about 15 Å.
In vivo regulation of mucosal transport of H+ and HCO‐3 in the feline gall bladder
Authors: NILSSON B. , RÅDBERG G. , FRIMAN S. , THUNE A. , SVANVIK J.
Published: December 2008

In the gall bladder of a fasting subject, a decline in the pH of the contents occurs due to secretion of H+ from the mucosa. In this study in anaesthetized cats, the gall bladder lumen was perfused with a bicarbonate buffer bubbled with 4% CO2 in air. During basal conditions, the Pco2 always rose while the pH and [HCO‐3] fell in the buffer when passing through the gall bladder lumen, indicating a continuous secretion of H+ by the mucosa. This H+ secretion was enhanced by stimulation of the respective sympathetic nerves and was blocked by intraluminal amiloride. Intravenous infusion of vasoactive intestinal peptide (VIP) raised the pH and [HCO‐3] in the buffer during the passage through the gall bladder lumen, indicating a secretion of bicarbonate from the mucosa. In view of the presence of sympathetic and VIP immunoreactive nerve fibres in the gall bladder wall and VIP receptors on the luminal epithelial cells, the study demonstrates that there are functional grounds for physiological variations in the secretion of H+ and HCO‐3 by the gall bladder mucosa. These variations may be important for the solubility of calcium salts in the gall bladder contents.
Effects of Lactobacillus plantarum and Staphylococcus xylosus on the Quality Characteristics of Dry Fermented Sausage “Sucuk”
Authors: Kaban G. , Kaya M.
Published: December 2008

ABSTRACT:  The effect of starter culture, containing the strains Lactobacillus plantarum GM77 and Staphylococcus xylosus GM92, isolated from traditional sucuk, on the quality characteristics of dry fermented sausage (sucuk) during ripening period was studied. The microbiological (lactic acid bacteria, Micrococcus/Staphylococcus, Enterobacteriaceae) and physicochemical (pH, aw, NPN, TBARS) properties and volatile compounds, extracted by solid phase microextraction and analyzed by gas chromatography‐mass spectrometry, were determined in sucuk samples with starter culture and in the control group (without starter culture). Both starter culture and ripening period had significant effects on lactic acid bacteria, Micrococcus/Staphylococcus counts, and pH and aw values (P < 0.01). The highest value for nonprotein nitrogen (NPN) was observed to occur in samples with starter culture (P < 0.05). TBARS value increased during ripening, the highest value was determined at 14th day in samples with starter culture. Among volatile compounds, terpenes were the major group in sucuk. Other volatile compounds (aldehydes, ketones, sulfur compounds, acids, esters, aliphatic hydrocarbons, aromatic hydrocarbons, and alcohols) can be found in fewer amounts. While the use of starter culture was affecting a few compounds, ripening period had affected most of the compounds.
Kinetics of an Acid‐Base Catalyzed Reaction (Aspartame Degradation) as Affected by Polyol‐Induced Changes in Buffer pH and pKa Values
Authors: Chuy S. , Bell L.N.
Published: December 2008

ABSTRACT:  The kinetics of an acid‐base catalyzed reaction, aspartame degradation, were examined as affected by the changes in pH and pKa values caused by adding polyols (sucrose, glycerol) to phosphate buffer. Sucrose‐containing phosphate buffer solutions had a lower pH than that of phosphate buffer alone, which contributed, in part, to reduced aspartame reactivity. A kinetic model was introduced for aspartame degradation that encompassed pH and buffer salt concentrations, both of which change with a shift in the apparent pKa value. Aspartame degradation rate constants in sucrose‐containing solutions were successfully predicted using this model when corrections (that is, lower pH, lower apparent pKa value, buffer dilution from the polyol) were applied. The change in buffer properties (pH, pKa) from adding sucrose to phosphate buffer does impact food chemical stability. These effects can be successfully incorporated into predictive kinetic models. Therefore, pH and pKa changes from adding polyols to buffer should be considered during food product development.
In vitro Digestibility and Glycemic Response of Potato Starch is Related to Granule Size and Degree of Gelatinization
Authors: Parada Javier , Aguilera José M.
Published: December 2008

ABSTRACT:  Starch granule microstructure affects the digestion of starch and its nutritional impact; however, the exact relationship between both factors is not clear. This study reports quantitative relationships between granule size (length and polygonal area), degree of gelatinization (DG), in vitro digestibility (by enzymatic methods), and glycemic response of potato starch granules gelatinized to various extents by heating at several constant temperatures in the range of 55 to 65 °C. DG measured by differential scanning calorimetry was closely related with heating temperature (R2= 0.997), size parameters of granules (measured by image analysis), in vitro digestion, and in vivo glycemic response (R2 of adjusted models > 0.9); shape parameters of granules (measured by image analysis) were not related with DG. Results demonstrate that DG of starch strongly affects its digestibility in vitro, and may influence the postpandrial glycemic response. Future studies should be performed to investigate the effect of potato starch gelatinization on the nutritional impact at other temperatures and in more complex matrices.
Gymnosiphon marieae sp. nov. (Burmanniaceae) from Madagascar, a species with tepal‐mediated stigmatic extension
Authors: Cheek Martin , Williams Sue , Brown Andrew
Published: December 2008

Gymnosiphon marieae Cheek sp. nov. from Madagascar is described and its conservation status assessed. The discovery of tepal‐mediated stigmatic extension in Gymnosiphon is reported.
Fluidic Engineering Challenges in the Development of an Electronic-Based DNA Identification System
Authors: Chafin D. , Murante R. , Greco R. J. , Hainon J. , Seabridge S. , VanDerMeid K. , Tiller C. , Connolly D. Michael
Published: December 2008

Integrated Nano-Technologies, LLC (INT) has spent the last three and a half years developing a novel electronic based DNA identification system. In addition to combining DNA with microelectronics to form sensors that respond to, and identify DNA sequences in target organisms; this system relies heavily on the manipulation and delivery of small volumes of fluids. These fluids facilitate both the biological and chemical reactions required by the devices processes. The Company has encountered fluidic engineering challenges throughout the development of the system including: • pump accuracy and delivery; • material incompatibilities; • adhesive intrusion; • reaction waste collection; • micro mixing/channel design. In this presentation, the challenges and the approaches taken to overcome them will be presented, as well as a device overview.
Rarefaction and Compressibility Effects on Steady or Transient Gas Flows in Microchannels
Authors: Colin Ste´phane
Published: December 2008

An analysis of the different significant length scales allows us to show the major part played by rarefaction in gas microflows, and the different flow regimes encountered in microchannels. The main theoretical and experimental results from the literature about steady pressure-driven gas microflows are summarized. Because it is very frequent in microchannels, the slip flow regime is more detailed and the question of appropriate choice of boundary conditions is discussed. It is shown that using second-order boundary conditions allows us to extend the applicability of the slip flow regime to higher Knudsen numbers that are usually relevant to transition regime. The case of pulsed flows is also presented, for this kind of flow is frequently encountered in micropumps. The influence of slip on the frequency behavior (pressure gain and phase) of microchannels is illustrated. When subjected to sinusoidal pressure fluctuations, microdiffusers reveal a diode effect which depends on the frequency. This diode effect may be reversed, when the depth is shrunk from a few hundred to a few micrometers. Thermally driven flows in microchannels are also described. They are particularly interesting for vacuum generation, using microsystems without moving parts.
Integrating Nanoscale Effects Into Micro and Macrosystems
Authors: Chen Gang , Wang Jinbo
Published: December 2008

Micro and macrosystems, as represented by microchannels and millichannels, have characteristic length scales much longer than those required to observe “size effects” manifested in nanostructures. How can one explore nanoscale effects to benefit micro and macrosystems? This paper first discusses nanoscale heat transfer effects and then uses a few examples to illustrate some potential ways to integrate nanoscale effects into micro and macrosystems.
State of the Art on Pulsating Heat Pipes
Authors: Groll Manfred , Khandekar Sameer
Published: December 2008

In recent years, thermal management of microelectronics is becoming a major feasibility bottleneck and has shown the limitations and shortcomings of conventional solutions. Market expetations are posing a simultaneous challenge of increased power levels coupled with high heat fluxes. Active and passive systems incorporating mini-/micro channel flows are gaining ground to meet the challenges. Both single phase and two-phase flows are under consideration with the latter proving to be better alternatives. Inline with these developments are the Pulsating Heat Pipes (PHPs), which are very attractive entrants in the family of closed passive two-phase heat transfer systems. Research activity in this area has steadily increased after their introduction. These apparently simple looking cooling devices have offered considerable challenges in phenomenological and theoretical understanding. These devices have already shown very high promise for terrestrial applications. They also have a potential for thermal control applications for space. Yet, complete design rules and optimization procedures are still not available. This paper highlights major progress and milestones achieved in the development of this promising technology of pulsating heat pipes in the last decade. A comprehensive review of design rules and modeling strategies available so far is presented. All the influence parameters affecting the thermal performance are explained in detail. Some recommendations for future research are also made.
Electrokinetic-Based Microfluidic Processes in Lab-on-a-Chip Devices
Authors: Li Dongqing
Published: December 2008

Most microfluidic processes in lab-on-a-chip devices are electrokinetic processes. Fundamental understanding of the electrokinetic based microfluidic processes is key to the design and process control of lab-on-a-chip devices. This paper will review basics of the electrical double layer field, and three key on-chip microfluidic processes: electroosmotic flow, sample mixing and sample dispensing.