bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of canine skeletal muscle and hindlimb blood flow in acute anemia
Authors: Kubes P. , Chapler C. K. , Cain S. M.
Published: April 2011

Redistribution of blood flow away from resting skeletal muscle does not occur during anemic hypoxia even when whole body oxygen uptake is not maintained. In the present study, the effects of sympathetic nerve stimulation on both skeletal muscle and hindlimb blood flow were studied prior to and during anemia in anesthetized, paralyzed, and ventilated dogs. In one series (skeletal muscle group, n = 8) paw blood flow was excluded by placing a tourniquet around the ankle; in a second series (hindlimb group, n = 8) no tourniquet was placed at the ankle. The distal end of the transected left sciatic nerve was stimulated to produce a maximal vasoconstrictor response for 4-min intervals at normal hematocrit (Hct.) and at 30 min of anemia (Hct. = 14%). Arterial blood pressure and hindlimb or muscle blood flow were measured; resistance and vascular hindrance were calculated. Nerve stimulation decreased blood flow (p < 0.05) in the hindlimb and muscle groups at normal Hct. Blood flow rose (p < 0.05) during anemia and was decreased (p < 0.05) in both groups during nerve stimulation. However, the blood flow values in both groups during nerve stimulation in anemic animals were greater (p < 0.05) than those at normal Hct. Hindlimb and muscle vascular resistance fell significantly during anemia and nerve stimulation produced a greater increase in vascular resistance at normal Hct. Vascular hindrance in muscle, but not hindlimb, was less during nerve stimulation in anemia than at normal Hct. The data indicate that (i) maximal sympathetic stimulation produced a significant decrease in both skeletal muscle and hindlimb blood flow during anemia, (ii) the reduction in blood flow in these areas was less with sympathetic stimulation during anemia than at normal Hct., and (iii) the anemic stimulus (Hct. = 14%) does not activate maximal sympathetic vasoconstrictor tone in the skeletal muscle.
Reversal of pulmonary hypoxic vasoconstriction with pentoxifylline and aminophylline in isolated lungs
Authors: Hakim Tawfic S.
Published: April 2011

Pentoxifylline (Pent) is a xanthine known to improve erythrocyte deformability and thought to have little effect on smooth muscle tone. In this study I examined the direct effects of Pent on the pulmonary vasculature of isolated lungs and compared them with the effects of aminophyliine. The object was to study whether Pent can reverse the hypoxic pressor response (HPR) by its hemorheological property. Changes in pulmonary arterial pressure (Pa) of isolated lungs (pigs and rats) perfused at constant flow rate were monitored to reflect changes in vascular resistance. During normoxia, injection of Pent (5 mg/kg animal weight) in pig lungs depressed the Pa from 12.8 ± 1.8 to 8.1 ± 0.8 mmHg (1 mmHg = 133.3 Pa); whereas during hypoxia, Pa was depressed from 34.0 ± 2.3 to 12.3 ± 1.4 mmHg. To identify the mechanism of this vasodepressor effect (being either vasodilation or improved erythrocyte deformability), I tested the effect of Pent in lungs perfused with cell-free perfusate. In these plasma-perfused lungs, the vasodepressor effects of Pent were similar to those observed during blood perfusion (slight depression in Pa during normoxia, but large during hypoxia). Similar experiments in blood and plasma perfused pig lungs revealed that aminophylline (5 mg/kg) also produced similar vasodepressor responses. The effects of Pent in rat lungs were comparable; no effect during normoxia, but a depressor effect during hypoxia. Vasoconstriction in pig lungs induced by angiotensin infusion was also abolished by Pent. These results suggest that xanthines (including Pent) attenuate the HPR by relaxing smooth muscle tone; thus Pent as a hemorheological agent was not helpful in identifying the importance of erythrocyte deformability in HPR. The results, however, may provide some insight into the role of adenosine and cyclic nucleotides in HPR.
Cardiac effects produced by long-term stimulation of thoracic autonomic ganglia or nerves: implications for interneuronal interactions within the thoracic autonomic nervous system
Authors: Butler C. , Watson-Wright W. M. , Wilkinson M. , Johnstone D. E. , Armour J. A.
Published: April 2011

Electrical stimulation of an acutely decentralized stellate or middle cervical ganglion or cardiopulmonary nerve augments cardiac chronotropism or inotropism; as the stimulation continues there is a gradual reduction of this augmentation following the peak response, i.e., an inhibition of augmentation. The amount of this inhibition was found to be dependent upon the region of the heart investigated and the neural structure stimulated. The cardiac parameters which were augmented the most displayed the greatest inhibition. Maximum augmentation or inhibition occurred, in most instances, when 5–20 Hz stimuli were used. Inhibition of augmentation was overcome when the stimulation frequency was subsequently increased or following the administration of nicotine or tyramine, indicating that the inhibition was not primarily due to the lack of availability of noradrenaline in the nerve terminals of the efferent postganglionic sympathetic neurons. Furthermore, as infusions of isoproterenol or noradrenaline during the period of inhibition could still augment cardiac responses, whereas during the early peak responses they did not, the inhibition of augmentation does not appear to be due primarily to down regulation of cardiac myocyte β-adrenergic receptors. The inhibition was modified by hexamethonium but not by phentolamine or atropine. Inhibition occurred when all ipsilateral cardiopulmonary nerves connected with acutely decentralized middle cervical and stellate ganglia were stimulated, whereas significant inhibition did not occur when these nerves were stimulated after they had been disconnected from the ipsilateral decentralized ganglia. Taken together these data indicate that the inhibition of cardiac augmentation which occurs during relatively long-term stimulation of intrathoracic sympathetic neural elements is due in large part to nicotinic cholinergic synaptic mechanisms that lie primarily in the major thoracic autonomic ganglia. They also indicate that long-term stimulation in intrathoracic sympathetic neural elements with frequencies as low as 2 Hz may augment the heart as much as higher stimulation frequencies, depending upon the structure stimulated and the cardiovascular parameter monitored.
Adipose tissue glyceride synthesis in patients with hyperapobetalipoproteinemia
Authors: Teng B. , Forse A. , Rodriguez A. , Sniderman A.
Published: April 2011

Adipose tissue was obtained at thoracotomy in five control patients with valvular heart disease, all of whom were free of coronary artery disease and all of whom were normolipidemic with normal low density lipoprotein apolipoprotein B levels, and eight patients with coronary artery disease, all of whom had hyperapobetalipoproteinemia. In both groups, the rates at which linoleic acid and palmitic acid were incorporated into diglyceride and triglyceride were determined in vitro. The data indicate that fatty acid incorporation into adipose tissue glycerides was twice as rapid in controls as in patients with hyperapobetalipoproteinemia. By contrast there was no difference between the groups in the rate of net lipolysis of adipocyte glyceride. The data at hand do not establish the mechanism responsible for the difference in synthesis between normal subjects and patients with hyperapobetalipoproteinemia, but this may explain the delayed chylomicron triglyceride clearance previously observed in the disorder.
Ventricular arrhythmias following coronary artery occlusion in the streptozotocin diabetic rat
Authors: Beatch G. N. , McNeill J. H.
Published: April 2011

The following investigation was designed to assess whether or not streptozotocin diabetes has an influence on the number and severity of ventricular arrhythmias following coronary artery occlusion in the conscious rat. In addition, electrocardiogram and haemodynamic data were compared between streptozotocin diabetic groups and control. Diabetes was induced in male Sprague–Dawley rats with streptozotocin (55 mg/kg iv) and left anterior descending coronary artery ligation was performed either 6 or 9 weeks later. Rats were allowed to recover from preparative surgery for 1 week prior to ligation. Streptozotocin diabetes (untreated or insulin controlled) appeared to have little influence on the variables tested. When exposed to equivalent degrees of ischaemia (the rat is a microangiopathy-resistant species), the streptozotocin diabetic rat heart was not appreciably more prone to arrhythmias of any type compared with control.
Neural control of canine colon motor function: studies in vitro
Authors: Gonda T. , Daniel E. E. , Kostolanska F. , Oki M. , Fox J. E. T.
Published: April 2011

The responses of strips of the canine colon to stimulation of intrinsic nerves and to the probable mediators of these nerves were studied in vitro. Studies were carried out using longitudinal and circular muscle strips from proximal and distal colon with field stimulation and addition of agents to the bath. Overall, these and other studies in vivo suggested that acetylcholine was an ubiquitous mediator of neural excitation. Norepinephrine had mixed inhibitory and excitatory effects, the latter only in circular muscle. Inhibitory effects of norepinephrine seemed to be both pre- and post-synaptic but no evidence that it was released by field stimulation was obtained. Substance P had excitatory effects chiefly by release of acetylcholine. It, in addition to norepinephrine, at least in circular muscle, deserves evaluation as the mediator of noncholinergic excitation to high frequency field stimulation. Although vasoactive intestinal peptide sometimes had inhibitory effects, these were incomplete and inconsistent. However, further evaluation of its possible role as a nonadrenergic, noncholinergic inhibitory mediator is required to determine if it is involved as one component in the response. Few qualitative differences existed between responses of various regions of the colon to potential neuromediators, although there were some consistent differences between responses of longitudinal and circular muscle. Some differences existed in responses obtained earlier in vivo and in vitro. In particular, inhibitory effects following excitation by substance P on field stimulation were found only in vivo. Nonadrenergic, noncholinergic inhibitory responses to field stimulation were consistently present only in vitro. These differences have not been explained.
Differential behaviour of 25-hydroxyvitamin D3 24-hydroxylase and 1-hydroxylase in response to protein synthesis inhibitors and cytochrome P-450 inhibitors
Authors: Kung M. , Kooh S. W. , Paek W. , Fraser D.
Published: April 2011

To characterize 25-hydroxyvitamin D3 24-hydroxylase and 25-hydroxyvitamin D3 1-hydroxylase, the activities of the two enzymes were measured in the presence of two types of inhibitors. The effect of protein synthesis inhibitors on 25-hydroxyvitamin D3-stimulated 24-hydroxylase activity in 1-hydroxylating rat kidneys perfused in vitro was tested. Actinomycin D (4 μM) and cytoheximide (10 μM) each abolished 25-hydroxyvitamin D3 24-hydroxylase synthesis when added at the start of perfusion but not when added 4 h later; they did not affect 25-hydroxyvitamin D3 1-hydroxylase activity. The effects of cytochrome P-450 inhibitors on the two enzyme activities were then studied in vivo. Metyrapone and SKF-525A (50 mg/kg body weight) each inhibited 25-hydroxyvitamin D3 24-hydroxylase at 6 and 24 h; in contrast 1-hydroxylase increased and was 5 times the control value at 24 h. Finally, the in vitro effects of six cytochrome P-450 inhibitors at concentrations ranging from 10−7 to 10−3 M on enzyme activities in renal mitochondrial preparations were compared. Both enzymes were inhibited by all of the inhibitors, but inhibition of 25-hydroxyvitamin D3 24-hydroxylase was consistently greater than that of 25-hydroxyvitamin D3 1-hydroxylase. These studies demonstrate that 24-hydroxylation and 1-hydroxylation respond differently to protein synthesis inhibitors and to cytochrome P-450 inhibitors. The findings are consistent with the hypothesis that the two enzyme activities are associated with different cytochrome P-450 moieties.
Hepatic uptake of indocyanine green and perfusion rate in rats: effect of age and albumin concentration
Authors: Montgomery Patrick R. , Sitar Daniel S.
Published: April 2011

Liver blood flow and hepatic uptake of some indicator substances have been reported to fall with age in both rats and humans. We used an isolated liver system, which was perfused in one pass with hemoglobin free buffer, to investigate the effect of albumin concentration, buffer flow rate, and age upon hepatic clearance of the dye, indocyanine green. We measured the half-life of a bolus of indocyanine green given intravenously to male Sprague–Dawley rats aged 10 and 24 months and then examined its clearance in vitro using their isolated perfused livers. After perfusion, the livers were homogenized and separated into subcellular fractions. The mean liver weight declined significantly (young, 19.7 ± 2.9 g vs. old, 13.9 ± 2.6 g; p < 0.02). In vivo the indocyanine green clearance was reduced in the aged rats (3.2 ± 1.0 vs. 5.1 ± 1.7 mL/min; p < 0.05). In the isolated perfused liver system, extraction ratio showed an inverse curvilinear correlation with albumin concentration and buffer flow rate, but did not differ with age. Hepatic protein content and dye subcellular localization did not differ between the two groups. In conclusion, the fall in indocyanine green clearance in vivo is not paralleled by the ability of the organs to extract the dye in vitro, and likely reflects a decline in hepatic mass and blood flow.
Postsynaptic potentiation and desensitization in frog neuromuscular junction
Authors: Glavinqvić M. I.
Published: April 2011

The fractional increase in ACh responses that occurs at the beginning of each train of iontophoretically applied ACh pulses has been examined at the frog neuromuscular junction at room temperature, in the presence of active cholinesterase, during desensitization produced by a rapid sequence (every 20 s) of short (5 Hz, 5 s) iontophoretic trains of ACh. The fractional increase in ACh responses, which is used as an indicator of postsynaptic potentiation, becomes progressively greater with ACh application, often markedly (>100%), although ACh responses are greatly reduced (as much as 90%) owing to desensitization. Clearly postsynaptic potentiation can exist concomitantly with desensitization. In addition, the dose–response curve is shifted to the right and its maximal response is diminished. The shift in the dose–response curve to the right, which can explain greater postsynaptic potentiation, is unlikely to be caused by accumulation of "monoligand-bound ACh receptor complexes," since experiments were done with active cholinesterase. The shift probably results from a greater number of desensitized receptors which, because of their large affinity for ACh molecules, serve as "high affinity traps." A small decrease of the maximal dose–response suggests only a small fractional decrease in the number of activable receptors, whereas a large shift to the right indicates a large fractional increase in the number of desensitized receptors. It appears that prior to ACh application only a small fraction of all receptors are desensitized. Alternatively, the shift to the right occurs because the cooperative action of ACh on receptors increases during desensitization.
Comparison between pentobarbital- and muscimol-induced feeding in satiated sheep
Authors: Seoane J. R. , Bédard L. , Caron N.
Published: April 2011

Twenty sheep were used to study the mechanisms by which the intracerebral administration of pentobarbital and of muscimol induces feeding in ruminants. Injections of 1 μmol calcium induced a weak feeding response at 1 h postinjection compared with control values (108 vs. 63 g, p < 0.05). Injections of 78 μmol pentobarbital and of 100 nmol muscimol elicited strong feeding responses (p < 0.01). A preinjection of 1 μmol calcium reduced the response to pentobarbital by about 40% but did not affect the response to muscimol. Administration of 1.1 mmol sodium chloride reduced the effect to pentobarbital by about 60% but only partially decreased the effect to muscimol. Administration of picrotoxin, a GABA antagonist, slightly decreased the feeding response to pentobarbital and to muscimol. Administration of γ-vinyl GABA, an inhibitor of the enzyme GABA transaminase, did not affect feeding behavior of sheep at any of the doses tested (0–10 μmol). Injections of γ-vinyl GABA followed by equimolar injections of GABA failed to provoke any feeding response. The data suggest that pentobarbital and muscimol may induce feeding by acting on a similar hypothalamic receptor complex but by different mechanisms. The lack of effect of GABA itself remains unexplained.
Human chorionic gonadotropin and luteinizing hormone-releasing hormone reverse the blockade of ovulation in pregnant mare's serum gonadotropin-primed immature rats by the anti-androgenic drug, hydroxyflutamide
Authors: Chandrasekhar Yallampalli , Armstrong David T.
Published: April 2011

The present study was designed to examine mechanism(s) of the anti-ovulatory action of the anti-androgen, hydroxyflutamide (OH-F). Prepubertal rats were treated with 4 IU pregnant mare's serum gonadotropin (PMSG) (day −2) to induce first estrus and ovulation. They received OH-F in sesame oil or oil alone at 08:00 and 20:00 h on day 0 (the day of proestrus) and ovulations were assessed on the morning of day 1. Eighty-three percent of control animals ovulated with a mean of 7.7 ± 1.1 corpora lutea per rat. Hydroxyflutamide blocked ovulation in all but 2 of the 12 rats receiving this drug alone. All the OH-F treated rats that received 5 and 25 IU human chorionic gonadotropin (hCG) ovulated with means ± SEM of 9.1 ± 0.1 and 7.3 ± 1.4 corpora lutea per rat, respectively. The dose of 0.2 IU hCG was essentially ineffective, while the effect of 1.0 IU hCG was intermediate. At the dose of 20 ng and above (100 and 500 ng) luteining hormone-releasing hormone (LHRH) completely overcame the ovulation blockade in the OH-F treated animals, while a 4-ng dose was ineffective. At 18:00 h on the day of proestrus, serum LH levels in control animals were 17.56 ± 2.60 ng/mL, which were 920% above basal levels (1.90 ± 0.13) indicating a spontaneous LH surge. This surge was suppressed in OH-F treated rats. Injection of LHRH, at the dose of 20 ng and above, reinstated the LH release in OH-F treated animals. Thus, the anti-androgen, OH-F, inhibits ovulation in PMSG-treated immature rats through its interference with the preovulatory LH surge; the inhibition can be reversed by hCG or LHRH. Hydroxyflutamide does not appear to interfere at the level of the pituitary, but may have direct action at the hypothalamic and (or) extrahypothalamic sites involved in the generation of positive feedback signals that control LH release.
Concentration effect of soluble dietary fibers on postprandial glucose and insulin in the rat
Authors: Vachon Carol , Jones John D. , Wood Peter J. , Savoie Laurent
Published: April 2011

The effects of different soluble fibers on blood glucose and insulin responses to voluntary meals in the rat were investigated. Rats (165–180 g) were adapted for 2 weeks to a fiber-free control diet or fiber diets made by dilution of the fiber-free diet with the fiber. Fibers and concentrations used were carboxymethylcellulose (1.25, 2.5, and 5%), guar gum, oat β-glucan (2.5, 5, and 7.5%), and mustard mucilage (5, 10, and 15%) as the soluble fibers, and cellulose (20%) as the insoluble fiber. Meal challenges (0.75 g/100 g body weight offered for consumption within a period of 15 min) were made with the adaptation diet. Soluble fibers reduced food intake and growth with a concentration effect, while cellulose increased food intake. All fibers reduced dry matter and nitrogen digestibilities but had no effect on the protein efficiency ratio. Only carboxymethylcellulose (at 5%) reduced postprandial glycemia at 30 min (p < 0.05). Cellulose had no effect on plasma insulin which was markedly reduced with a concentration effect by all soluble fibers (except mustard mucilage) in the following decreasing order: carboxymethylcellulose, guar gum, β-glucan, and mustard mucilage. The effect of fibers seemed closely related to the viscosity of fiber solutions in the presence of the diet ingredients. The present findings demonstrate the positive effect of fibers on postprandial insulinemia but with only a slight effect on glycemia. They indicate that the physicochemical interaction of the fibers with other dietary ingredients is important.
Impact of the hepatic arterial buffer response on splanchnic vascular responses to intravenous adenosine, isoproterenol, and glucagon
Authors: Lautt W. Wayne , D'Almeida Mark S. , McQuaker Janet , D'Aleo Lillian
Published: April 2011

Hepatic arteries (HA) and superior mesenteric arteries (SMA) of cats anesthetized with pentobarbital responded to direct intra-arterial infusion of isoproterenol, adenosine, and glucagon with dose-related vasodilation. In response to intravenous infusion, however, the HA failed to dilate significantly, while the SMA dilated thus elevating portal blood flow. The lack of dilation of the HA was due to the HA buffer response to the elevated portal blood flow, that is, elevation of portal flow causes the HA to constrict. When a clamp was used to return SMA flow to control levels during infusion of the drugs, the HA showed significant dilation to all three agents. Thus, HA vascular responses to i.v. drugs can only be assessed if portal flow is known, since the net effect is dependent upon direct action of the drug on the HA as well as the indirect effect of any drug-induced change in portal flow. None of the agents tested altered the magnitude of the HA buffer response obtained during i.v. infusions, but the effects of other agents on the buffer response remain unknown and must be considered in any tests of i.v. administered drugs. Bolus i.v. injections produce results on the HA flow that are uninterpretable.
The effect of 3-methylindole on the quantity and functional quality of lung surfactant
Authors: Kirkland James B. , Bray Tammy M.
Published: April 2011

Acute bovine pulmonary edema is a naturally occurring lung disease caused by 3-methylindole (3MI), a ruminal fermentation product of tryptophan. Morphological and in vitro studies have suggested that 3MI causes abnormalities in phospholipid synthesis. The present study was designed to investigate the effect of 3MI on the quantity and functional quality of surfactant using the goat as an experimental model. Following intravenous infusion of 3MI, goats were killed at 6-, 18-, and 30-h intervals. The lungs were removed and intracellular surfactant, in the form of lamellar bodies, and extracellular surfactant from alveolar lavage were quantified. 3MI treatment did cause modest changes in the lamellar body phospholipid pools, decreasing the quantity of phosphatidylcholine and the proportion of palmitate in this fraction. The quantity of lavage phospholipids was not significantly affected. There was an increase in the protein content of the lavage, reflecting the presence of edema. The functional quality of the surfactant isolated from the lavage fraction was tested in vitro using a pulsating bubble surfactometer. 3MI infusion decreased the ability of surfactant to lower the surface tension of an air bubble at maximum radius and during compression.
Fractal and Markov behavior in ion channel kinetics
Authors: French Andrew S. , Stockbridge Lisa L.
Published: April 2011

Kinetic analysis of ion channel recordings attempts to distinguish the number and lifetimes of channel molecular states. Most kinetic analysis assumes that the lifetime of each state is independent of previous channel history, so that open and closed durations are Markov processes whose probability densities are sums of exponential decays. An alternative approach assumes that channel molecules have many configurtions with widely varying lifetimes. Rates of opening and closing then vary with the time scale of observation, leading to fractal kinetics. We have examined kinetic behavior in two types of channels from human and avian fibroblasts, using a maximum likehood method to test the dependence of rates on observational time scale. For both channels, openings showed mixed fractal and Markov behavior, while closings gave mainly fractal kinetics.
Three types of slow inward currents as distinguished by melittin in 3-day-old embryonic heart
Authors: Bkaily G. , Jacques D. , Yamamoto T. , Sculptoreanu A. , Payet M. D. , Sperelakis N.
Published: April 2011

Membrane slow inward currents of 3-day-old embryonic chick single heart cells were investigated using the whole-cell patch clamp technique. In a solution containing only Na+ ions and in the presence of tetrodotoxin and Mn2+, the inward current–voltage relationship presented two maxima, confirming the existence of two different voltage-dependent slow inward currents. The first type, a fast transient slow inward current (Isi (ft)), was activated from a holding potential of −80 mV and showed fast activation and inactivation. This current was highly sensitive to melittin (10−8 M) and insensitive to low concentrations of desmethoxyverapamil ((−)D888, 10−9–10−6 M). Depolarizing voltage steps from a holding a potential of −50 mV activated two components of the slow inward current, i.e., a slow and a sustained current (Isi(sts)) that showed a slow inactivation followed by a slow inactivation and a sustained component. Melittin at a high concentration (10−4 M) completely blocked the slow transient component (Isi(st)) and left unblocked the sustained component (Isi(s)). Both components (Isi(st) and Isi(s)) were blocked by verapamil (10−5 M) and low concentrations of (−)D888 (10−8–10−6 M).
Effect of hyocholic acid on the prevention and dissolution of biliary cholesterol crystals in mice
Authors: Dusserre J. P. , Montet A. M. , Montet J. C.
Published: April 2011

Gallstone prevention and dissolution were studied in a mouse model of cholesterol cholelithiasis using hyocholic acid (3α, 6α, 7α-trihydroxy-5β-cholanic acid). Addition of hyocholic acid, 0.1 or 0.3%, in the lithogenic diet (1% cholesterol + 0.5% cholic acid) prevented the formation of cholesterol monohydrate crystals in 70 and 90% of cases, respectively. On the other hand, chow diet supplemented with 0.1 or 0.3% hyocholic acid dissolved cholesterol crystals in lithiasic mice in, respectively, 80 and 100% of cases within 12 days. In both protocols, biles were largely supersaturated with cholesterol; lecithin–cholesterol lamellar liquid crystals were responsible for the transport of the excess cholesterol content. The percentage of hydrophilic bile salts (hyocholic acid, hyodeoxycholic acid, β-muricholic acid) in bile, although moderate (15–50% of total bile salts), appears to induce such liquid crystalline dispersion. This study demonstrates that the balance between hydrophilic and hydrophobic bile salts plays a major role in the prevention and dissolution of cholesterol crystals. It is also shown that the desaturation of biliary cholesterol is not a prerequisite for gallstone dissolution.
Pharmacological actions of the calcium antagonist propyl-methylenedioxyindene in skinned vascular smooth muscle
Authors: Wong Wai-Shiu , Rahwan Ralf G.
Published: April 2011

Previous studies provided strong evidence that propyl-methylenedioxyindene (pr-MDI) interfered with calcium at an intracellular site. To further characterize the mechanism of action of pr-MDI, its pharmacological actions on chemically skinned vascular smooth muscle were examined. Rat caudal artery strips were chemically skinned with saponin (0.15 mg/mL for 1 h). The efficiency of the skinning was evidenced by a loss of contractile response to 74 mM K+. The intactness of the regulatory and contractile proteins was ascertained by the ability of the skinned tissue to contract in response to Ca2+ (free Ca2+ concentration of 10−4 or 10−6 M). Caffeine (25 mM) induced contraction was used as an index of the functional integrity of the sarcoplasmic reticulum in the skinned preparations. Contraction of the skinned artery with a free Ca2+ concentration of 10−6 M was significantly obtunded by 1 × 10−4 M trifluoperazine (a calmodulin antagonist) but not by 1 × 10−4 M pr-MDI. Contraction of the skinned artery evoked by 25 mM caffeine in the absence of extracellular calcium was significantly obtunded by 1 × 10−4 M pr-MDI but not by 1 × 10−6 M nifedipine (a calcium channel blocker). The results indicate that pr-MDI acts intracellularly to block calcium mobilization from the sarcoplasmic reticulum without directly interfering with the regulatory and contractile proteins.
Energy balance and facultative diet-induced thermogenesis in mice fed a high-fat diet
Authors: Richard Denis , Boily Pierre , Dufresne Marie-Claude , Lecompte Martin
Published: April 2011

The present study was aimed at studying energy balance in mice fed a high-fat diet. Albino mice were divided into three groups. One group had free access to the stock diet, whereas the two other groups consumed a high-fat diet. One of the high-fat fed groups was fed ad libitum, whereas the other was offered a restricted amount of the same diet so that its energy intake was comparable to the group of mice given the stock diet. Energy balance measurements, which included indirect calorimetry and carcass analysis, were performed. Brown adipose tissue (BAT) properties were also investigated. The results show that gains in both body weight and fat were higher in mice that had free access to high-fat diet than in mice fed the stock diet. In animals given a restricted amount of the high-fat diet, fat gain increased, whereas protein gain was reduced in comparison with animals fed the stock diet. Unrestricted access to the high-fat diet led to an increase in both energy intake and energy gain. As revealed by both slaughter and indirect calorimetry techniques energy expenditure was, in high-fat fed mice, 40% higher than in animals fed either stock or a restricted amount of high-fat diet. Nadolol was shown to suppress a large part of the elevated metabolic rate seen in mice fed an unrestricted high-fat diet. In those mice, BAT mitochondrial GDP binding was also increased. In summary, the present results confirm that adaptive diet-induced thermogenesis (DIT) develops in mice made hyperphagic by an energy-dense palatable diet. The present study provides further evidence that adaptive DIT is mediated by the sympathetic nervous system and involves BAT. Finally, it appears that the extent to which adaptive DIT develops is related to the degree of hyperphagia.
Pharmacologic characterization of cirazoline-activated inositol phospholipid hydrolysis in rat brain cortical slices
Authors: Li Peter P. , Sibony David , Warsh Jerry J.
Published: April 2011

Interaction of cirazoline, an imidazoline derivative, with α1-adrenoceptor coupled inositol phospholipid hydrolysis was characterized in rat brain cortical slices. Norepinephrine, a full α1-agonist, and phenylephrine, a partial α1-agonist, on inositol phospholipid hydrolysis were included for comparison. Norepinephrine produced a fourfold stimulation of inositol phospholipid hydrolysis, whereas cirazoline and phenylephrine caused only submaximal responses (40–60%) when compared with norepinephrine. The stimulation of inositol phospholipid hydrolysis by cirazoline was completely blocked by the α1-adrenoceptor antagonist prazosin, but not by selective α2- or β-adrenoceptor antagonists. Furthermore, the norepinephrine dose–response curve was shifted to the right in the presence of cirazoline, without affecting the maximal response. These results suggest that cirazoline behaves as a partial agonist at brain α1-adrenoceptors linked to inositol phospholipid hydrolysis.
The effect of prior exercise and caffeine ingestion on metabolic rate and hormones in young adult males
Authors: Poehlman Eric T. , LaChance Pierre , Tremblay Angelo , Nadeau André , Dussault Jean , Thériault Germain , Després Jean-Pierre , Bouchard Claude
Published: April 2011

The purposes of this study were to examine (a) the effects of acute exercise on metabolic rate 24 and 48 h postexercise and (b) the interaction of acute exercise and the thermic effect of caffeine on metabolic rate and hormonal changes during the late postexercise recovery period. In six young males, who were regular consumers of caffeine, resting energy expenditure was measured before and after caffeine (5 mg∙kg−1) and placebo ingestion under the following conditions: (i) control (e.g., no prior exercise), (ii) 24 h postexercise, and (iii) 48 h postexercise. Blood samples were drawn for plasma glucose, insulin, glycerol, free fatty acids, catecholamines, and thyroid hormones (triiodothyronine, thyroxine, and free thyroxine). Results showed that acute exercise did not exert a detectable effect on resting metabolic rate in the late postexercise recovery period, that is, resting metabolic rate was similar among the conditions of control (1.17 ± 0.12 kcal∙min−1), 24 h postexercise (1.16 ± 0.12), and 48 h postexercise (1.16 ± 0.11). Caffeine ingestion increased metabolic rate (~7%), but the thermic effect was not different among the experimental conditions. Plasma insulin and norepinephrine were lower after caffeine ingestion, whereas an increase in plasma free fatty acids was noted. Other hormones and substrates did not change significantly in response to caffeine ingestion. Furthermore, the hormonal and substrate milieu was not significantly different 24 and 48 h postexercise when compared with the control condition. Our results support the view that acute exercise does not alter the resting metabolic rate in the late postexercise recovery period. Moreover, acute exercise does not potentiate the thermic effect of caffeine in the late postexercise recovery in caffeine-tolerant males.Key words: caffeine, resting metabolic rate, acute exercise, hormones, substrates.
α1-Adrenoceptor activity in arterial smooth muscle following congestive heart failure
Authors: Forster Christine , Carter Susan L. , Armstrong Paul W.
Published: April 2011

The interactions between yohimbine (selective α2-antagonist) with noradrenaline (mixed agonist) and phenylephrine (selective α1-agonist) were studied in the canine dorsal pedal artery in an attempt to characterize the peripheral vascular response to adrenergic agents before and after the development of congestive heart failure in the dog. The contractile responses of the dorsal pedal artery to potassium chloride were also examined. Both noradrenaline and phenylephrine contracted the dorsal pedal artery in a concentration-dependent manner before and at peak heart failure, the responses to the agonists being enhanced at heart failure. The responses of the artery to potassium were not modified by congestive heart failure. Yohimbine caused concentration-dependent antagonism of noradrenaline, without altering the magnitude of the maximum response, providing pA2 values ranging from 8.26 to 7.06 against low and high concentrations of noradrenaline, respectively, before heart failure development. Following heart failure, the pA2 values for yohimbine against noradrenaline remained unchanged, but slopes from the Arunlakshana–Schild plots were significantly different from unity, implying a noncompetitive antagonism. The pA2 values of yohimbine against phenylephrine were at least 10 orders of magnitude lower than those against noradrenaline. After congestive heart failure, yohimbine was even less effective against high concentrations of phenylephrine. These findings suggest that enhanced vasoconstriction during heart failure results, in part, from increased α1-adrenoceptor mechanisms in peripheral arterial smooth muscle.Key words: vascular α-adrenoceptors, congestive heart failure, dorsal pedal artery, yohimbine, noradrenaline.
Vasopressin receptors and inositol trisphosphate production in blood vessels of spontaneously hypertensive rats
Authors: Larivière Richard , Baribeau Johanne , St-Louis Jean , Schiffrin Ernesto L.
Published: April 2011

To understand the regulation of vasopressin (AVP) receptors in spontaneous hypertension, we investigated the pressor response of AVP in the perfused mesenteric vasculature, AVP binding sites in the membrane preparation of the same vascular bed, and the production of inositol trisphosphate (InsP3) stimulated by AVP in the aorta of spontaneously hypertensive rats (SHR), Wistar–Kyoto rats (WKY), and Wistar rats (WR) at different ages (4–16 weeks). Plasma AVP concentrations were similar in SHR, WKY, and WR at all ages. The density of AVP vascular binding sites was significantly higher in WKY than in SHR and WR at 12 weeks. Receptor affinity was similar in all strains. The pressor response of the mesenteric vasculature to AVP was similar in the three strains of rats at 4 weeks (prehypertensive stage) and increased progressively in SHR compared with WKY and WR at 8 and 12 weeks of age by 43 and 35%, respectively, and by more than 80% at 16 weeks of age (established hypertensive stage). There was no difference in vascular sensitivity to AVP. A significantly increased pressor response to a supramaximal dose of norepinephrine was also found at 16 weeks in SHR, but not in younger rats. InsP3 production in the aorta in response to AVP was increased in SHR at 8, 12, and 16 weeks, compared with WKY and WR. These results suggest that the vascular response to AVP is increased in SHR, in spite of decreased or normal density of binding sites compared with WKY or WR. The increased responsiveness to AVP in SHR may be mediated in part by the enhanced activity of AVP receptor-coupled phospholipase C, resulting in increased membrane phosphoinositide breakdown and inositol trisphosphate production, which may play a role in the elevation of blood pressure in SHR.Key words: vascular reactivity, vasopressin binding sites, phosphoinositide breakdown, phospholipase C, high blood pressure.
Inhibition of platelet-activating factor induced renal hemodynamic and tubular dysfunctions with L-655,240, a new thromboxane–prostaglandin endoperoxide antagonist
Authors: Hébert R. L. , Sirois P. , Plante G. E.
Published: April 2011

The continuous infusion or bolus injection of the platelet-activating factor (PAF) is associated with profound hypotension, marked reductions of renal plasma flow, glomerular filtration, and urinary sodium excretion. All these effects are inhibited by blocking PAF receptors. To examine further the potential mediators of PAF on renal function, we utilized L-655,240 (6 mg/kg, intravenously), a thromboxane–prostaglandin endoperoxide antagonist, to study the systemic and renal response to PAF (0.8 μg/kg, intravenously) in the anesthetized dog, using clearance methodology. PAF decreased blood pressure from 115 ± 7 to 54 ± 4 mmHg (1 mmHg = 133.3 Pa), renal plasma flow from 105 ± 6 to 74 ± 56 mL/min, and glomerular filtration from 43 ± 3 to 32 ± 1 mL/min. PAF also reduced urine volume from 1.1 ± 0.2 to 0.4 ± 0.1 mL/min, and urinary sodium from 158 ± 7 to 86 ± 7 μequiv./min. L-655,240 alone had no significant effect on blood pressure, renal plasma flow, and filtration rate, at any dose. However, the 6-mg/kg dose resulted in a slight elevation of diuresis, from 1.1 ± 0.2 to 1.9 ± 0.1 mL/min, and urinary sodium, from 134 ± 13 to 212 ± 19 μequiv./min. All doses of L-655,240 blocked the effect of PAF on blood pressure. However, the two lower doses of this antagonist (1 and 3 mg/kg) failed to prevent the PAF-induced fall of renal plasma flow and filtration rate, and attenuated the effect on urinary sodium in a dose-dependent manner. These results indicate that the renal vasoconstriction and antinatriuretic effects of PAF are probably mediated by thromboxane A2 and (or) prostaglandin endoperoxides in the dog. L-655,240 represents therefore a potent inhibitor of PAF-induced renal dysfunctions, and may be of significant interest to explore further the physiology and pathophysiology of PAF.Key words: platelet-activating factor, renal function, lipid mediators, thromboxane antagonist, shock.
Hypothalamic cyclic AMP after the injection of ovarian steroids into ovariectomized rats
Authors: Zubin P. , Taleisnik S.
Published: April 2011

The effect of ovarian steroids on the concentration of adenosine 3′,5′ -cyclic monophosphate (c AMP) in the hypothalamus was studied in ovariectomized rats. Ovariectomized rats exhibited a lower cAMP concentration than intact rats. The administration of a single dose of estradiol benzoate (50 μg/kg body weight) resulted 3 days later in a rise of cAMP values, but levels did not reach those observed in estrous rats. Progesterone (2 mg/rat) injected 3 days after the priming dose of estradiol benzoate produced 4 h later no further changes in hypothalamic cAMP. The changes in hypothalamic cAMP concentration induced by estrogen treatment depend, at least in part, on noradrenergic inputs, since they were prevented by the injection of the norepinephrine synthesis inhibitor, diethyldithiocarbamate. In addition, administration of the β-blocking agent, propranolol, to estradiol- and estradiol–progesterone-treated rats lowered the concentration of cAMP in the hypothalamus in a dose-dependent manner. In contrast, the administration of an α-blocking agent, phenoxybenzamine, had no effect at the tested concentration. The results of this study indicate that estrogen increases cAMP concentration in the hypothalamus by a noradrenergic mechanism involving β-receptors. Moreover, the findings suggest that estrogen induces an increase in the number of β-receptor sites, whereas progesterone increases the apparent propranolol sensitivity for these receptor sites.Key words: cAMP, hypothalamus, ovarian steroids, adrenergic receptors, propranolol.
Heterogeneity in responses of isolated monkey arteries and veins to atrial natriuretic peptide
Authors: Kawai Yasuaki , Ohhashi Toshio
Published: April 2011

Regional differences in responses of isolated monkey arteries and veins to atrial natriuretic peptide were investigated by recording isometric tension. Addition of atrial natriuretic peptide (4 × 10−12 to 4 × 10−8 M) produced a concentration-dependent relaxation in isolated monkey arteries and veins. No significant difference was observed between the responses to rat and human atrial natriuretic peptides. A marked heterogeneity in responses to rat atrial natriuretic peptide, however, was observed in arterial preparations. The decreasing order of the response was as follows: renal > pulmonary > femoral = mesenteric > coronary > middle cerebral > basilar arteries. A heterogeneity in the relaxation produced by atrial natriuretic peptide was also observed in monkey veins. The decreasing order of the response was as follows: pulmonary > mesenteric = portal > femoral > renal = inferior caval veins. On the other hand, 10−5 M sodium nitroprusside caused a maximal relaxation in all monkey arteries and veins used. In the middle cerebral, basilar, and coronary arteries, the relaxant effects of rat atrial natriuretic peptide on KCl-induced contraction were significantly smaller than those on the preparations contracted by an agonist such as prostaglandin F2α. These results suggest that there exist profound regional vasorelaxant selectivities of atrial natriuretic peptide in isolated monkey arteries and veins.Key words: atrial natriuretic peptide, artery, vein, vasodilation, monkey.
Ouabain prevents loss of autoregulation in rat pial arterioles caused by reoxygenation after a brief hypoxic episode
Authors: Kettler J. , Ong B. Y. , Bose D.
Published: April 2011

Pial arteriolar diameter changes inversely with changes in systemic arterial blood pressure. Such changes are consistent with autoregulatory functions. These responses are reduced by a brief period of hypoxia followed by reoxygenation. By using an open cranial window preparation we assessed the changes in pial arteriolar diameters during blood pressure changes in rats induced by hemorrhage and reinfusion of blood, before and after a brief period of hypoxia. The slopes of the changes in pial arteriolar diameter as a function of mean arterial blood pressure were −0.47 ± 0.26 μm/mmHg (mean ± SD; 1 mmHg = 133.3 Pa) before hypoxia and −0.11 ± 0.23 μm/mmHg after hypoxia in the untreated rats. In ouabain-treated rats, corresponding slopes were −0.42 ± 0.24 and −0.46 ± 0.22 μm/mmHg. The observed protective effects of ouabain might be a blockade of the Na–K pump in the sarcolemma of the vascular smooth muscle.Key words: vascular smooth muscle, electrogenic sodium pump, metabolic inhibition.
Effects of rearing temperature and level of food intake on organ size and tissue composition in piglets
Authors: Heath Martha E.
Published: April 2011

Piglets are particularly susceptible to cold and nutritional stress because of their poor insulation and low body fat. The purpose of this study was to examine how ambient temperature and level of food intake affect development in piglets. Thirty-two piglets were reared individually from 14 to 56 days of age in either a cold (10 °C) or a warm (35 °C) environment. Two feeding regimes, restricted and ad libitum, were used to assess the effect of food intake on organ mass. The ad libitum fed pigs in both environments gained weight at the same rate. Paired t-tests of organ weights of ad libitum fed pigs revealed that the mass of the heart, liver, kidneys, stomach, and small intestine, and total nitrogen and the length of the small intestine were greater in cold-reared than in warm-reared littermates of the same body weight. The skin mass and total fat mass, the lengths of the body, extremities, and individual long bones, and the total surface area were greater in warm-reared than in cold-reared individuals. A regression analysis showed body weight was the most important determinant of size for all tissues measured except fat mass, which was affected slightly more by rearing temperature. Of the organs and tissue components that differed in size in warm- and cold-reared pigs, heart, kidney, stomach, skin, nitrogen, and fat mass, and small intestine length and surface area were generally affected more by rearing temperature than by level of food intake. Liver and small intestine mass and femur length were affected more by level of food intake. Only total fat, nitrogen, and skin mass were significantly affected by rearing temperature and only liver mass was affected significantly by level of food intake. Fat distribution in warm-reared pigs was different than in cold-reared pigs.Key words: thermal environment, body composition, diet, growth.
Effect of atrial natriuretic factor on blood–brain barrier permeability
Authors: Nag Sukriti , Pang Stephen C.
Published: April 2011

Recent studies have demonstrated receptors for atrial natriuretic factor on endothelium of intracerebral vessels. The physiological role of these receptors is not known. The present study was undertaken to determine whether atrial natriuretic factor has an effect on blood–brain barrier permeability to protein and ions using horseradish peroxidase and lanthanum as markers of permeability alterations. This study does not demonstrate a significant effect of atrial natriuretic factor on blood–brain barrier permeability mechanisms in steady states.Key words: blood–brain barrier, atrial natriuretic factor, horseradish peroxidase, lanthanum, ultrastructure.