bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions between plasma proteins and pulmonary surfactant: pulsating bubble studies
Authors: Keough Kevin M. W. , Parsons Caroline S. , Tweeddale Martin G.
Published: April 2011

The influence of human albumin, α-globulin, and fibrinogen on the actions of porcine pulmonary surfactant in a pulsating bubble surfactometer has been investigated. All three proteins detracted from the ability of the surfactant to adsorb to the air–water interface. The proteins also reduced the ability of surfactant to lower the opening pressures of bubbles cycling between different sizes in suspensions of surfactant. This was equivalent to restricting the ability of the surfactant to achieve low surface tension during compression of the surface. Of the three proteins, globulin competed most effectively with surfactant during the adsorption process, and albumin competed the least effectively. The proteins also may have interfered with the processes of surface refinement, which usually yields a monolayer enriched enough in dipalmitoyl phosphatidylcholine to achieve very low surface tension (very low opening pressures in the bubbles). Of the three proteins tested, albumin was least deleterious to surface refining whereas globulin and fibrinogen appeared to be about equally detrimental to the process.Key words: pulmonary surfactant, surface tension, adsorption, adult respiratory distress syndrome, surfactant inhibition.
Intrinsic origin of atrioventricular nodal functional properties in rabbits
Authors: Gendreau Raymond , Billette Jacques , Zhao Jie , Couture Réjean
Published: April 2011

The goal of the present study was to document the intrinsic origin of atrioventricular nodal functional properties (recovery time, facilitation, and fatigue) in two groups of six superfused isolated rabbit heart preparations. These properties were determined from recovery curves (A2H2 versus H1A2 intervals) obtained with previously defined periodic premature stimulation sequences performed before and after autonomic blockade demonstrated effective with the injection of agonists. In group 1 preparations, the muscarinic cholinergic and β-adrenergic receptors were blocked with atropine (1 mg/L) and propranolol (1 mg/L), respectively. The blockade reduced the facilitation and increased the fatigue by the direct membranous effect of propranolol, To avoid this effect in group 2 preparations, propranolol was replaced by sotalol (5 mg/L), which in combination with atropine altered neither the presence nor the magnitude of the functional properties. These results show that the origin of the three nodal functional properties is independent from the autonomic nervous system.Key words: atrioventricular node, recovery time, fatigue, facilitation, autonomic blockade.
The role of aberrant hypothalamic opiatergc function in generating polycystic ovaries in the rat
Authors: Carriere Paul D. , Farookhi Riaz , Brawer James R.
Published: April 2011

Treatment of adult female rats with estradiol valerate produces an intractable hypothalamic impairment that ultimately results in anovulatory acyclicity and polycystic ovaries. Evidence from our laboratory suggests that the hypothalamic impairment compromises regulation of the endogenous opioid system engendering a persistent opiatergic suppression of gonadotropin-releasing hormone secretion, which is subsequently reflected in a chronically low pituitary content of gonadotropin-releasing hormone receptors. If such is the case, inhibition of opiatergic transmission should improve the gonadotropin-releasing hormone pattern resulting in an improvement in the pituitary content of gonadotropin-releasing hormone receptors, and in an amelioration of the polycystic condition. We, therefore, treated rats with the polycystic ovarian condition, with daily injections of naltrexone. Within 1 week, there was a significant increase in the pituitary content of gonadotropin-releasing hormone receptors and a marked improvement in ovarian morphology, indicating that the hypothalamic opiatergic system is chronically active, and contributes significantly to the polycystic ovarian condition.Key words: hypothalamus, opiates, infertility, ovary, polycystic ovaries.
Ovarian follicular development and regression
Authors: Leung Peter C. K.
Published: April 2011

Many exciting developments in mammalian reproductive research with far-reaching consequences have occurred in recent years. To highlight the significance of some of these developments, a symposium on the theme of ovarian follicular development and regression was organized, and held at the joint meeting of the American Physiological Society and the Canadian Physiological Society, in Montréal in October 1988. Several leading researchers, from both Canada and the U.S.A., in various aspects of ovarian research, participated in the symposium. The topics of discussion ranged from the role of growth factors and novel intraovarian regulators during follicular development, to molecular aspects of ovarian hormone production, to the functional regression of the corpus luteum. It is expected that the following proceedings will serve as a reference for researchers concerned with reproductive endocrinology as well as providing a foundation for future collaborative study.
Atrial natriuretic factor attenuates sympathetic neuroeffector responses in hindlimb vasculature of rabbits
Authors: Patel K. P.
Published: April 2011

To determine whether atrial natriuretic factor (ANF) affects vasoconstrictor responses to electrical stimulation of sympathetic nerves or intra-arterial norepinephrine (NE), changes in perfusion pressure were measured during lumbar sympathetic nerve stimulation (LSNS, 1–8 Hz), or administration of NE (50–200 ng), in an isolated constant flow-perfused hindlimb of chloralose-anesthetized rabbit before and after intra-arterial infusion of ANF (0.5 ng∙mL−1∙min−1). ANF significantly attenuated responses to LSNS (relative potency, RP = 0.65) and to NE (RP = 0.47). We conclude that ANF attenuates vasoconstrictor responses to both LSNS and NE. Thus ANF alters sympathetic nervous system mediated changes in vascular resistance possibly at the neuroeffector site.Key words: atrial natriuretic factor, sympathetic nerve stimulation, vasculature.
Developmental increase in the inotropic and cyclic AMP response to isoproterenol in embryonic and newly hatched chicks
Authors: Nakazawa Ken , Kusuya Yutaka , Shigenobu Koki
Published: April 2011

The cyclic adenosine 3′,5′-monophosphate (cyclic AMP) levels of ventricles isolated from 15- to 20-day-old chick embryos and 0- to 3-day-old hatched chicks were compared to clarify the mechanism underlying the change in sensitivity to isoproterenol during perinatal developmental stages when the functional sympathetic innervation has been completely achieved. Isoproterenol produced a positive inotropic effect on ventricles isolated from both embryonic and hatched chicks, but the ventricles from the hatched chicks were more sensitive. At both developmental stages sotalol was an equipotent antagonist of isoproterenol. 3-Isobutyl-1-methylxanthine (IBMX) produced an increment in the contractile force of the ventricles at both stages, but the ventricles from the hatched chicks responded to lower doses of IBMX. The reactivity to isoproterenol in increasing cyclic AMP level was significantly higher in the hatched ventricles than in the embryonic ventricles. The results suggest that the different sensitivities to isoproterenol between embryonic and newly hatched chick ventricles may be due to some changes in the process for cyclic AMP production.Key words: chick ventricle, development, β-adrenergic sensitivity, cyclic AMP.
Derecruitment in cat liver: extension of undistributed parallel tube model to effects of low hepatic blood flow on ethanol uptake
Authors: Greenway C. V. , Bass L.
Published: April 2011

Previous studies showed two deviations from the predictions of the undistributed parallel tube model for hepatic uptake of substrates: a small deviation at high flows and a large deviation at low flows. We have examined whether these deviations could be described by a single correction factor. In cats anesthetized with pentobarbital, a hepatic venous long-circuit technique with an extracorporeal reservoir was used to vary portal flow and hepatic venous pressure, and allow repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cat's blood volume. Hepatic uptake of ethanol was measured over a wide range of blood flows and when intrahepatic pressure was increased at low flows. This uptake could be described by the parallel tube model with a correction for hepatic blood flow: [Formula: see text]. In 22 cats, [Formula: see text], k = 0.021 ± 0.0015 when flow (F) was in millilitres per minute per 100 g liver, and Km = 150 ± 20 μM when ĉ is the log mean sinusoidal concentration. (1 − e−kF) represents the proportion of sinusoids perfused and metabolically active. A dynamic interpretation of this proportion is related to intermittency (derecruitment) of sinusoidal flow. Half the sinusoids were perfused at a flow of 33 mL/(min∙100 g liver) and the liver was essentially completely perfused (> 95%) at the normal flow of 150 mL/(min∙100 g liver). Derecruitment was not changed by raising hepatic venous pressure, and it was not related to hepatic venous resistance.Key words: liver circulation, ethanol metabolism, liver blood flow, sinusoidal perfusion, portal pressure.
Effect of dietary fibers on glycemia and insulinemia and on gastrointestinal function in rats
Authors: Bégin F. , Vachon C. , Jones J. D. , Wood P. J. , Savoie L.
Published: April 2011

The effects of purified and semipurified dietary fiber supplements on glycemia and insulinemia were measured simultaneously with their effects on digestive tract function in the rat. An insoluble fiber (cellulose) and four soluble fibers (guar gum, carboxymethylcellulose, mustard mucilage, and oat β-glucan) were added separately to a fiber-free solid diet and fed to Sprague–Dawley rats for 10 days. Guar gum and oat β-glucan reduced the food intake, whereas cellulose increased it. Guar gum reduced weight gain. Cellulose increased the protein efficiency ratio. After a 13-h fast, glycemia and insulinemia were measured 45, 90, 210, and 360 min after the beginning of a voluntary short meal. Addition of fibers did not change the glycemic response, but soluble fibers significantly decreased insulinemia 45 min after the meal. All fibers significantly delayed gastric emptying, cellulose and mustard mucilage being the most effective. Dry matter contents of the small intestine were increased especially by guar gum and oat β-glucan. All fibers seemed to slow down small intestinal transit and decreased intestinal absorption. In the present experimental situation, both gastric and intestinal components played a role in the hypoinsulinic effect of dietary fibers. The intestinal component appeared to be more determinant for all soluble fibers, except mustard mucilage where the gastric component was more important.Key words: dietary fibers, glycemia, insulinemia, gastrointestinal function, digestion.
Effect of cycle frequency and excursion amplitude on work done by rat diaphragm muscle
Authors: Syme D. A. , Stevens E. D.
Published: April 2011

Strips of isolated rat diaphragm muscle were attached to a servomotor–transducer apparatus, and the muscle length was cycled in a sinusoidal fashion about the length at which maximum isometric twitch force was developed, Lo. The amplitude of the length displacement (excursion amplitude) and rate of cycling were varied between 3 and 13% Lo and 1–4 Hz respectively. The muscle was tetanically stimulated (100 Hz, supramaximal voltage, stimulus duration (duty cycle) 20% of the length cycle period) during the shortening stage of the imposed length cycle at the phase that yielded maximum net positive work. The force and displacement of the muscle were recorded. Work per cycle was calculated from the area of the loop formed by plotting force against length for one full stretch–shorten cycle. Work per cycle decreased, but power increased, as cycle frequency was increased from 1 to 4 Hz. Maximum work done per cycle was about 12.8 J/kg at a cycle frequency of 1 Hz. Maximum mean power developed was about 27 W/kg and occurred at a cycle frequency of 4 Hz. Work and power were maximum at an excursion amplitude of 13% of Lo (i.e., Lo ± 6.5%). Measured work and power output are considerably less than values estimated from length–tension and force-velocity curves.Key words: rat, diaphragm, work, power, duty cycle.
Ionic mechanisms of action of GABA on dorsal and ventral root myelinated fibers: effects of K+ channel blockers
Authors: Morris M. E. , Liske S.
Published: April 2011

Excitability changes evoked by the inhibitory neurotransmitter, GABA (γ-aminobutyric acid) in myelinated axons of dorsal and ventral roots of the isolated bullfrog sciatic nerve were compared in the absence and presence of K+ channel blockers. Half-maximal A-fiber responses to a 0.5-Hz stimulation of the whole nerve were recorded from individual roots. Direct applications of Ringer with raised K+ levels to the site of stimulation caused increases in excitability of both dorsal and ventral root fibers, which resembled those evoked in the ventral root by the GABA agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]ol). The increases in dorsal root fiber responses produced by GABA were depressed by tetraethylammonium (TEA) (3 mM), 4-aminopyridine (4-AP) (50 μM), Cs (2 mM), and Ba (1 mM). Ventral root fibers were less consistently affected. The early component of GABA-evoked excitability increases was depressed by 4-AP, Cs, and Ba, but greatly augmented by TEA. THIP-evoked changes in the excitability of the dorsal and ventral root fibers were, respectively, depressed and enhanced by TEA. The augmenting effect of TEA on the early component of GABA agonist effects on the ventral root fibers is attributed to their high resting K+ conductance and the presence of a slowly inactivating, fast K+ current (If1). The depressant effects of K+ channel blockade on depolarizing components of agonist-evoked changes in dorsal and ventral root responses indicate interference with release and (or) sensitivity to K+ and a possible contribution from a mechanism involving voltage-dependent delayed rectifier K+ currents.Key words: K+ channel blockade, γ-aminobutyric acid agonists, K+ accumulation, K+ application, excitability.
Altered release of growth hormone from dispersed adenohypophysial cells of streptozotocin diabetic rats. II. Effects of a phorbol ester and secretagogues which increase cyclic AMP
Authors: Sheppard M. S. , Eatock B. A. , Bala R. M.
Published: April 2011

We have shown in the companion paper that somatotrophs dispersed from streptozotocin diabetic rats exhibit altered sensitivity to the natural hypothalamic controlling hormones, growth hormone releasing factor and somatostatin. We have further studied the effects on growth hormone release from dispersed adenohypophysial cells of normal and streptozotocin diabetic rats of stimulation by compounds that increase cyclic 3′,5′-adenosine monophosphate formation or inhibit its breakdown and of a phorbol ester. The cells of the diabetic rats had no change in sensitivity in response to either cholera toxin or forskolin. A phosphodiesterase inhibitor caused an equal GH release from cells of both diabetic and normal animals after 60 min of incubation. There was no change in sensitivity of the cells of diabetic animals or in the maximal reponse of these cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate when compared with normal cells. A low calcium medium that blocked growth hormone releasing factor stimulated growth hormone release from normal rat cells also blocked it from the cells of the diabetic rats. These results suggest that the defect in response of the somatotrophs of diabetic animals is specific and only occurs with the hypothalamic hormones and not with other secretagogues.Key words: growth hormone, diabetes, streptozotocin, cyclic AMP, phorbol ester.
Biotransformation of glyceryl trinitrate and isosorbide dinitrate in vascular smooth muscle made tolerant to organic nitrates
Authors: Slack Christopher J. , McLaughlin Brian E. , Brien James F. , Marks Gerald S. , Nakatsu Kanji
Published: April 2011

It has been proposed that organic nitrates are prodrugs and biotransformation to a pharmacologically active metabolite (i.e., nitric oxide) must occur before the onset of vasodilation. If this postulated mechanism is correct, tolerance to organic nitrate-induced vasodilation might involve decreased biotransformation of organic nitrates by vascular smooth muscle. In this study, biotransformation of isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN) was estimated by measuring isosorbide mononitrate (ISMN) and glyceryl dinitrate (GDN), respectively, rather than the nitrate anion, because of a more sensitive method for measurement of ISMN and GDN. To test this hypothesis, isolated rabbit aortic strips (RAS) were made tolerant in vitro by incubation with 500 μM GTN or ISDN for 1 h. After a washout period and submaximal contraction with phenylephrine, the tissues were incubated with either 2.0 μM [14C]ISDN or 0.5 μM [14C]GTN for 2 min. ISDN- or GTN-induced relaxation of RAS was monitored and tissue parent drug and metabolite contents were determined by thin-layer chromatography and liquid scintillation spectrometry. ISDN- and GTN-induced relaxation of RAS and the metabolite concentrations were significantly less for both GTN- and ISDN-tolerant tissue compared with nontolerant tissue. These results are consistent with the hypothesis that organic nitrate biotransformation is required for organic nitrate-induced vasodilation.Key words: organic nitrates, glyceryl trinitrate, isosorbide dinitrate, biotransformation, prodrug, tolerance.
The effect of food protein-induced intestinal anaphylaxis on rate of transit
Authors: Maric M. , Gall D. G. , Scott R. B.
Published: April 2011

The aim of this study was to determine if the altered jejunal motility previously demonstrated in this animal model of food protein-induced intestinal anaphylaxis is (a) a localized (the jejunal site of challenge), or a generalized response of the small intestine, and (b) associated with more rapid aboral transit of intraluminal contents. Hooded–Lister rats, 100–150 g in weight, were sensitized by intraperitoneal injection of 10 μg egg albumin. Control rats were sham-sensitized. On day 7 rats were surgically prepared with six bipolar electrodes from duodenum to ileum and (or) a jejunostomy tube was positioned at the ligament of Treitz. On day 14, after an 18-h fast, recordings of myoelectric activity were obtained from four sensitized animals with electrodes from duodenum to ileum during a control period for 45 min after saline challenge and for 45 min after antigen challenge. Control (n = 25) and sensitized (n = 31) animals with only a jejunostomy had Na251CrO4 instilled through the jejunostomy in 0.5 mL of saline, with or without egg albumin, either during a fast or after a standard meal. Propulsion of isotope through the small bowel was allowed to progress for 15 min, the animals were sacrificed, and their gut was removed for division into eight equal segments of small intestine, cecum, and remaining colon. The radioactivity of each segment was determined in a gamma counter. Jejunal antigen challenge of sensitized animals was associated with diarrhea and disruption of the migrating myoelectric complex at electrode sites from duodenum to ileum, while placebo challenge caused neither diarrhea (p < 0.01) nor disruption of the migrating myoelectric complex (p < 0.05). In both the fasted and fed states, the geometric centre of transit was significantly (p < 0.05) greater in sensitized animals challenged with antigen than in control animals challenged with placebo or antigen, or in sensitized animals challenged with placebo. Food protein-induced intestinal anaphylaxis induces a generalized alteration of small intestinal motility not limited to the region of antigen exposure and is associated with an increased rate of aboral transit.Key words: intestine, intestinal transit, anaphylaxis, food allergy.
Nicardipine inhibits axon conduction but causes dual changes of acetylcholine release in the mouse motor nerve
Authors: Chang C. C. , Chiou L. C. , Hwang L. L. , Hong S. J. , Huang C. Y.
Published: April 2011

The effects of nicardipine, a dihydropyridine Ca2+-channel antagonist, on neuromuscular transmission and impulse-evoked release of acetylcholine were compared with those of nifedipine. In the isolated mouse phrenic nerve diaphragm, nicardipine (50 μM), but not nifedipine (100 μM), induced neuromuscular block, fade of tetanic contraction, and dropout or all-or-none block of end-plate potentials. Nicardipine had no significant effect on the resting membrane potential and the amplitude of miniature end-plate potentials but increased the frequency and caused the appearance of large size miniature potentials. The quantal contents of evoked end-plate potentials were increased. In the presence of tubocurarine, however, nicardipine depressed the amplitude of end-plate potentials. The compound nerve action potential was also decreased. It is concluded that nicardipine blocks neuromuscular transmission by acting on Na+ channels and inhibits axonal conduction. Nicardipine appeared to affect the evoked release of acetylcholine by dual mechanisms, i.e., an enhancement presumably by an agonist action on Ca2+ channels, like Bay K 8644 and nifedipine, and inhibition by an effect on Na+ channels, like verapamil and diltiazem. In contrast with its inactivity on the amplitude of miniature end-plate potentials, depolarization of the end plate in response to succinylcholine was greatly depressed. The contractile response of baby chick biventer cervicis muscle to exogenous acetylcholine was noncompetitively antagonized by nicardipine (10 μM), but was unaffected by nifedipine (30 μM). These results may implicate that nicardipine blocks the postsynaptic acetylcholine receptor channel by enhancing receptor desensitization or by a use-dependent effect.Key words: nicardipine, calcium channel antagonists, neuromuscular transmission, acetylcholine release, acetylcholine receptor desensitization.
Effects of neurotensin on motor patterns of canine duodenum and proximal jejunum
Authors: Bühner Sabine , Ehrlein H.-J.
Published: April 2011

The aim of this study was to clarify if small doses of neurotensin (2.5 and 5.0 pmol∙kg−1∙min−1, i.v.) in dogs alter the postprandial motor pattern of the duodenum in comparison with the adjacent jejunum. The intestinal motor patterns were quantified by means of closely spaced strain gauge transducers and a computerized method. An acaloric viscous meal of cellulose was used to induce postprandial motility. Gastric emptying was measured radiographically. During intravenous control infusion of saline, the characteristics of duodenal and jejunal motor pattern were significantly different. The duodenum contracted at a lower rate and showed a higher incidence of stationary contractions. The lower dose (2.5 pmol∙kg−1∙min−1) of neurotensin showed no significant effects, whereas the higher dose (5 pmol∙kg−1∙min−1) significantly slowed gastric emptying and altered the motor pattern of both intestinal segments in a similar manner. It reduced the number of contractions, shortened the contraction spread, increased the incidence of stationary contractions, and decreased the incidence of propagated contractions. The alterations of motility caused enhanced mixing of luminal contents. The differences in motor patterns seen in the control state between both intestinal segments were diminished during neurotensin. Data revealed no differences in sensitivity of the duodenum and jejunum to neurotensin. Results suggest that neurotensin is one of the gastrointestinal peptides involved in regulating intestinal contractile patterns.Key words: intestinal motility, gastrointestinal hormones, neurotensin, contractile patterns.
Morphology of the canine pyloric sphincter in relation to function
Authors: Daniel E. E. , Berezin I. , Allescher H. D. , Manaka H. , Posey-Daniel V.
Published: April 2011

The ultrastructure and immunocytochemistry of the canine distal pyloric muscle loop, the pyloric sphincter, were studied. Cells in this muscle were connected by gap junctions, fewer than in the antrum or corpus. The sphincter had a dense innervation and a sparse population of interstitial cells of Cajal. Most such cells were of the circular muscle type but a few were of the type in the myenteric plexus. Nerves were sometimes associated with interstitial cell profiles, but most nerves were neither close to nor associated with interstitial cells nor close to smooth muscle cells. Nerve profiles were characterized by an unusually high proportion of varicosities with a majority or a high proportion of large granular vesicles. Many of these were shown to contain material immunoreactive for vasoactive intestinal polypeptide (VIP) and some had substance P (SP) immunoreactive material. All were presumed to be peptidergic. VIP was present in a higher concentration in this muscle than in adjacent antral or duodenal circular muscle. Interstitial cells of Cajal made gap junctions to smooth muscle and to one another and might provide myogenic pacemaking activity for this muscle, but there was no evidence of a close or special relationship between nerves with VIP or SP and these cells. The absence of close relationships between nerves and either interstitial cells or smooth muscle cells leaves unanswered questions about the structural basis for previous observations of discrete excitatory responses or pyloric sphincter to single stimuli or nerves up to one per second. In conclusion, the structural observations suggest that this muscle has special neural and myogenic control systems and that interstitial cells may function to control myogenic activity of this muscle but not to mediate neural signals.Key words: vasoactive intestinal polypeptide, interstitial cells of Cajal, neuropeptides, gap junctions, substance P.
Interactions between peripheral-type benzodiazepine receptor ligands and an activator of voltage-operated calcium channels
Authors: Bolger Gordon T. , Abraham Shlomo , Oz Nissim , Weissman Ben Avi
Published: April 2011

The effects of the peripheral-type benzodiapine receptor (PBR) ligands Ro 5-4864 and PK 11195 were studied in the spontaneously beating guinea pig atrium and in a model for myocardial ischemia in the rat. In the former, Bay K 8644 produced positive chronotropic and inotropic responses; intracarotid administration of this agonist (5 or 10 μg kg−1) to anesthetized rats elicited a transient increase in mean arterial blood pressure accompanied by alterations in the ECG pattern. Ro 5-4864 and PK 11195 (10 μM) completely blocked the positive chronotropic effect of Bay K 8644 in the atrium, PK 11209, a structural analog of PK 11195 with a low affinity for PBR, was inactive, and the central benzodiazepine receptor ligand clonazepam had a marginal effect. Ro 5-4864 potentiated whereas PK 11195 inhibited the myocardial ischemia produced by Bay K 8644 in the rat. Furthermore, PK 11195 blocked the combined response to Bay K 8644 and Ro 5-4864. Addition of Ro 5-4864 (10 μM) to the organ bath potentiated the inotropic effect of Bay K 8644 in the atria; PK 11195 at the same concentration inhibited this effect. Clonazepam and PK 11209 were both inactive in this regard. Nifedipine, a potent calcium channel antagonist, competely blocked the inotropic and chronotropic responses to Bay K 8644. PK 11195 and Ro 5-4864 did not affect this action. These findings strongly suggest that there is a functional association between PBR and voltage-operated calcium channels in the guinea pig atrium and rat cardiovascular system.Key words: peripheral benzodiazepine receptors, dihydropyridines, voltage-operated calcium channels, Bay K 8644, heart.
Lipoprotein lipase activity in white adipose tissue of rats subjected to exercise–rest cycles
Authors: Deshaies Yves , Lortie Gilles , Richard Denis
Published: April 2011

This study was conducted to determine serum lipid levels and the activity of lipoprotein lipase in epididymal white adipose tissue of rats undergoing exercise training. During the 8-week period of treatment, one group of rats was kept sedentary and the remaining animals were exercise trained either continually (1 h of daily treadmill running) or intermittently (alternate weeks of daily running and inactivity). Exercise training, either continual or intermittent, decreased postprandial serum total and high-density lipoprotein cholesterol concentrations, which returned to sedentary levels in the intermittently trained animals following a week of rest. Lipoprotein lipase activity in whole epididymal adipose pad was lower in rats trained continually than in the sedentary group at the end of the treatment. The intermittent training program elicited large fluctuations in both the specific (per milligram of protein) and total (per tissue) activity of lipoprotein lipase in white adipose tissue. During rest periods, enzyme activity rose to levels that were higher than those of sedentary rats, whereas lipase activity was below that of sedentary animals following a week of running. In the last exercise–rest cycle, body weight gain of the intermittently trained rats was nearly abolished during the week of running, but it increased above that of sedentary animals during weeks of rest. The present results suggest that the modulation of lipoprotein lipase activity in white adipose tissue is one of the adaptations that take place to accommodate the fluctuations in the rate of energy deposition that occur in the rat during an intermittent training program.Key words: exercise training, cholesterol, white adipose tissue, lipoprotein lipase.
Possible role of blood insulin levels on glutathione S-transferase activities from different tissues of male rats
Authors: Carnovale Cristina E. , Monti Juan A. , Catania Viviana A. , Carrillo Maria C.
Published: April 2011

The activity of in vitro glutathione S-transferase towards 1-chloro-2,4-dinitrobenzene was examined in liver, renal cortex, and small intestine (duodenum, jejunum, ileum) after the in vivo treatment of male Wistar rats with streptozotocin or alloxan. The studies were performed at 2, 10, 24, and 48 h and 7 and 15 days after streptozotocin treatment or 24 and 48 h after alloxan treatment. The results indicated that while the blood levels of insulin–glucose did not show variations, there were no alterations of the glutathione S-transferase activity in the tissues tested. On the other hand, when the treatments caused modifications on blood insulin–glucose levels, there were changes of glutathione S-transferase activity in all tissues (except in the ileum) in such a way that a direct relationship between plasma insulin levels and glutathione S-transferase activity could be demonstrated. These results were also confirmed through insulin administration to control and diabetic rats. The data demonstrate a possible regulation of glutathione S-transferase activity by blood insulin and (or) glucose levels in the tissues tested.Key words: insulin, glutathione S-transferase, streptozotocin, alloxan.
New antiemetic drugs
Authors: Sanger G. J.
Published: April 2011

Three major areas of medicine are identified in which there is a need for new antiemetic drugs. These are the nausea and vomiting arising from gastrointestinal motility disturbances (functional dyspepsia, diabetic neuropathy, classical migraine), the sickness evoked by abnormal motion, and the severe emesis experienced by cancer patients as a result of certain cytotoxic therapies. For gastrointestinal-related nausea, selective stimulants of gut motility are suggested to form the basis for a new type of antiemetic therapy. In motion sickness, there has been progress in the understanding of the illness, but little advance in the development of new drugs that selectively prevent this type of sickness. In cancer chemo- and radio-therapy, the discovery that selective 5-HT3 (5-HT, 5-hydroxytryptamine) receptor antagonists can prevent severe cytotoxic-evoked emesis now promises to radically change the type of antiemetic therapy given to these patients. This type of antiemetic compound and the pharmacology of the new 5-HT3 receptor antagonists are, therefore, discussed in detail.Key words: emesis, gastric motility, 5-hydroxytryptamine, 5-HT3 receptors.
Naloxone's effect on the inotropic and chronotropic responses of isolated, electrically stimulated or spontaneously beating rat atria
Authors: Thornhill J. , Onge R. St. , Gregor L.
Published: April 2011

Experiments were conducted to determine (i) how naloxone administration alone could modify the inotropic (in electrically stimulated (ES) rat atria) and both the inotropic and chronotropic responses (in spontaneously beating (SB) rat atria) isolated from normotensive and hypotensive (hemorrhaged) rats, and (ii) how naloxone administration would modify the inotropic and chronotropic responses of isolated rat atria previously administered an opiate agonist (morphine), a muscarinic agonist (carbachol), or an α - and β-adrenergic agonist (noradrenaline). Naloxone (51–340 μM) added to ES atria caused a delayed but dose-related decrease in atrial tension (AT), whereas in SB atria, naloxone caused atrial heart rate (AHR) to fall and atrial tension (AT) to increase. Naloxone (68–340 μM), given to SB atria from acutely hypotensive rats, caused a similar increase in atrial tension as seen in the "normotensive" isolated (SB) atria and a similar decrease in atrial heart rate. Morphine sulphate (MS), 37–375 μM, administered to ES atria caused a delayed fall in AT, which was further decreased when naloxone (340 μM) was also added. In the SB atria, morphine caused a dose-related decrease in atrial heart rate whereas atrial tension increased. In SB preparations, atrial heart rate fell even further when naloxone was added to morphine compared with when morphine sulphate was given alone, whereas atrial tension was increased. Noradrenaline (3 or 12 μM) caused a positive, dose-related inotropic response in the ES atria, effects not influenced by the addition of naloxone. In the SB atria, naloxone caused no change in the dose-related increases in atrial tension and heart rate when combined with the lower dose of noradrenaline but decreased AT when combined with 12 μM noradrenaline, compared with when this dose of noradrenaline was given alone. Carbachol (683 nM – 1.37 μM) caused a dose-related decrease in atrial tension in ES atria, which was reversed completely by the addition of naloxone. In SB atria, carbachol decreased both atrial tension and heart rate, and with the addition of naloxone (340 μM), a further slight drop in atrial heart rate occurred, but concurrently, a marked rise in atrial tension was observed. The results indicate that naloxone can act with receptors directly within atrial tissue to cause changes in atrial tension and heart rate. The comparable delayed responses of morphine and naloxone suggest their effects are mediated by nonopiate receptors which, in time, cause decreases in calcium influx into the atria. The marked rise in atrial tension following naloxone administration in atria previously given carbachol suggest there is an interaction between naloxone- and carbachol-sensitive receptors in the atria. The net result of this interaction may again reflect a change (increase) in calcium influx into myocardial cells.Key words: rat atria, inotropy, chronotropy, morphine, carbachol, noradrenaline, acute hypotension.
Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs
Authors: Ogilvie Richard I. , Zborowska-Sluis Danuta
Published: April 2011

The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital- anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.Key words: mean circulatory filling pressure, vascular compliance, vascular capacitance, nifedipine, captopril.
Inhibitory innervation of colonic smooth muscle cells and interstitial cells of Cajal
Authors: Huizinga Jan D. , Berezin Irene , Daniel Edwin E. , Chow Edwin
Published: April 2011

The effect of neural inhibition on the electrical activities of circular and longitudinal colonic smooth muscle was investigated. In addition, a comparative study was carried out between circular muscle preparations with and without the "submucosal" and "myenteric plexus" network of interstitial cells of Cajal (ICC) to study innervation of the "submucosal" ICC and to investigate whether or not the ICC network is an essential intermediary system for inhibitory innervation of smooth muscle cells. Electrical stimulation of intrinsic nerves in the presence of atropine caused inhibitory junction potentials (ijps) throughout the circular and longitudinal muscle layers. The ijp amplitude depended on the membrane potential and not on the location of the muscle cells with respect to the ICC network. Neurally mediated inhibition of the colon resulted in a reduction in amplitude and duration of slow wave type action potentials in circular and abolishment of spike-like action potentials in longitudinal smooth muscle, both resulting in a reduction of contractile activity. With respect to mediation by ICC, the study shows (i) "submucosal" ICC receive direct inhibitory innervation and (ii) circular smooth muscle cells can be directly innervated by inhibitory nerves without ICC as necessary intermediaries. The reversal potential of the ijp in colonic smooth muscle was observed to be approximately −76 mV, close to the estimated potassium equilibrium potential, suggesting that the nerve-mediated hyperpolarization is caused by increased potassium conductance.Key words: enteric nerves, potassium conductance, pacemaker activity, VIP, inhibitory junction potential.
Acute insulin withdrawal contributes to ischemic heart failure in spontaneously diabetic BB Wistar rats
Authors: Lopaschuk Gary D. , Spafford Marguerite A.
Published: April 2011

The contribution of poor metabolic control to myocardial ischemic failure was determined in isolated working hearts from insulin-dependent BB Wistar rats. Removal of insulin treatment 24 h prior to study (uncontrolled diabetic rats) resulted in significant increases in serum glucose, serum fatty acids, and myocardial triglyceride, compared with animals in which insulin treatment was not withheld (insulin-treated diabetic rats). Isolated working hearts obtained from these two groups were subjected to a 40% reduction in coronary flow in the presence of a maintained metabolic demand (hearts were paced at 200 beats/min and perfused at an 80 mmHg (1 mmHg = 133.3 Pa) left aortic afterload, 11.5 mmHg left atrial preload). Within 15 min of ischemia, a significant deterioration of mechanical function occurred in the uncontrolled diabetic rats, whereas function was maintained in the insulin-treated diabetic rats. Oxygen consumption by the two groups of hearts was similar prior to the onset of ischemia and decreased during ischemia in parallel with the work performed by the hearts. This suggests that the accelerated failure rate in uncontrolled diabetic rat hearts is unlikely a result of an increased oxygen requirement. These data are a direct demonstration that acute changes in metabolic control of the diabetic can contribute to the severity of myocardial ischemic injury.Key words: diabetes, heart, ischemia, fatty acids.
No rarefaction of cerebral arterioles in hypertensive rats
Authors: Werber Andrew H. , Fitch-Burke MaryPat C. , Harrington David G. , Shah Jina
Published: April 2011

A reduction in the density of small arterioles (rarefaction) has been reported in several vascular beds of the spontaneously hypertensive rat (SHR). There have been conflicting reports on the existence of rarefaction in the pial vasculature of SHR. In this study, we determined whether there was rarefaction of pial arterioles in several models of hypertension. We studied SHR; two-kidney, one-clip Goldblatt hypertensive rats; deoxycorticosterone–salt hypertensive rats; and Dahl salt-sensitive rats fed high salt diet. The two groups of normotensive controls were Wistar–Kyoto rats and Dahl salt-sensitive rats fed low salt diet. The duration of hypertension was about 2 months. Density of first-, second-, third-, and fourth-order arterioles was determined by counting the number of vessels from enlarged photographs. We also measured the lengths of segments of the arterioles. We did not observe any evidence of rarefaction of arterioles in the pial vasculature in any of the hypertensive groups of rats. We conclude that (i) rarefaction of arterioles does not occur in the pial microvasculature after approximately 2 months of hypertension and (ii) rarefaction of pial arterioles does not account for abnormalities in the cerebral circulation of hypertensive rats such as protection of the blood–brain barrier or changes in autoregulation of cerebral blood flow.Key words: microcirculation, brain, vascular density.
Antilaminin IgG binds and interacts with cardiac cholinergic receptors
Authors: Bacman Sandra , Sterin-Borda Leonor , Lustig Livia , Denduchis Berta , Borda Enri
Published: April 2011

Antilaminin IgG bound to cholinergic muscarinic receptors of normal mice heart and simulated the biological effect of a cholinergic agonist. Antilaminin IgG interfered with the binding of the radiolabelled muscarinic antagonist, (−)-[3H]quinuclidinyl benzilate, in a noncompetitive fashion. The interaction of antilaminin IgG with the muscarinic cholinergic receptor increased production of cGMP and decreased production of cAMP. Antilaminin IgG also decreased the contractile tension of mouse atria. Both the mechanical and enzymatic effect of antilaminin IgG required the activation of the muscarinic cholinergic system because they were blunted by atropine and mimicked by acetylcholine.Key words: antilaminin IgG, cholinergic muscarinic receptors, cGMP, cholinergic binding assay, cAMP, heart contractility.
Role of β-adrenergic agonists in the control of vascular capacitance
Authors: Rothe Carl F. , Flanagan A. Dean , Maass-Moreno Roberto
Published: April 2011

The role of β-adrenergic agonists, such as isoproterenol, on vascular capacitance is unclear. Some investigators have suggested that isoproterenol causes a net transfer of blood to the chest from the splanchnic bed. We tested this hypothesis in dogs by measuring liver thickness, cardiac output, cardiopulmonary blood volume, mean circulatory filling pressure, portal venous, central venous, pulmonary arterial, and systemic arterial pressures while infusing norepinephrine (2.6 μg∙min−1∙kg−1), or isoproterenol (2.0 μg∙min−1∙kg−1), or histamine (4 μg∙min−1∙kg−1), or a combination of histamine and isoproterenol. Norepinephrine (an α- and β1-adrenergic agonist) decreased hepatic thickness and increased mean circulatory filling pressure, cardiac output, cardiopulmonary blood volume, total peripheral resistance, and systemic arterial and portal pressures. Isoproterenol increased cardiac output and decreased total peripheral resistance, but it had little effect on liver thickness or mean circulatory filling pressure and did not increase the cardiopulmonary blood volume or central venous pressure. Histamine caused a marked increase in portal pressure and liver thickness and decreased cardiac output, but it had little effect on the estimated mean circulatory filling pressure. Isoproterenol during histamine infusions reduced histamine-induced portal hypertension, reduced liver size, and increased cardiac output. We conclude that the β-adrenergic agonist, isoproterenol, has little influence on vascular capacitance or liver volume of dogs, unless the hepatic outflow resistance is elevated by agents such as histamine.Key words: β-adrenergic agonists, vascular capacitance, mean circulatory filling pressure, isoproterenol, histamine, liver sphincters.
The effect of reinnervation on the distribution of muscle fibre types in the tibialis anterior muscle of the mouse
Authors: Parry David J. , Wilkinson Ross S.
Published: April 2011

The distribution of fibre types in the tibialis anterior (TA) muscle of adult mice was examined by means of an immuno-histochemical approach, using monoclonal antibodies that recognize different myosin heavy chain isoforms. As has been reported previously, the superficial portion of TA contains almost exclusively type IIB fibres and is almost entirely glycolytic in nature. Following section of the lateral popliteal nerve and rotation of the proximal stomp to prevent rematching, it was found that the original pattern was virtually restored within 2 months. One possible explanation for this observation is that the activity pattern of peripheral and deep muscle fibres differs and that this aids in specification of muscle fibre type. Alternatively, the muscle fibres of the superficial portion of TA may be inherently resistant to an alteration of their phenotype with regard to expression of myosin heavy chain.Key words: myosin heavy chain, immunohistochemistry, plasticity, self-reinnervation, fibre types.
Urinary excretion of cGMP in response to atrial natriuretic peptide in dogs with acute pancreatitis
Authors: Levy Mortimer , Cernacek Peter
Published: April 2011

Previous studies have shown that when atrial natriuretic peptide (ANF) is given to anaesthetized dogs with hypovolemic acute pancreatitis, it will produce a diuresis and natriuresis but will not elevate the glomerular filtration rate (GFR). When the same dose of peptide is given to dogs equally hypovolemic (hemorrhage) but without pancreatitis, a brisk increment in GFR occurs. GFR will, however, rise in dogs with pancreatitis in response to other peptides, such as glucagon. In these studies we assessed cGMP excretion as a marker for ANF effect in both normal anaesthetized dogs and dogs with acute experimental pancreatitis. In each group, urinary output and sodium excretion increased significantly, but GFR rose only in the control group. Urinary excretion of cGMP rose equally and dramatically in both control and experimental animals. We conclude that GFR is prevented from rising in dogs with experimental pancreatitis following ANF, but this effect does not depend on depressed cGMP generation.Key words: cGMP urinary excretion, canine acute pancreatitis, atrial natriuretic peptide.