bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurogenic dilatation and constriction of rat superior mesenteric artery in vitro: mechanisms and mediators
Authors: Kannan M. S. , Seip A. E.
Published: April 2011

In the rat superior mesenteric arteries, the mechanical responses to perivascular nerve stimulation were characterized. The predominant response was contraction mediated by the release of norepinephrine, acting postjunctionally on α1-adrenoceptors. These frequency-dependent contractions were unaffected by the α2-selective adrenoceptor antagonist yohimbine, but were markedly attenuated by clonidine, the α2-selective adrenoceptor agonist. In the presence of prazosin, the α1-selective antagonist, a significant component of the nerve-mediated contraction was still present. At the concentrations used, prazosin, yohimbine, as well as clonidine acted as competitive antagonists of response to exogenous norepinephrine. This differential inhibition of norepinephrine- and nerve-mediated responses suggested the presence of distinct postjunctional adrenoceptors. The effects of clonidine and yohimbine are interpreted to arise from prejunctional modulation of norepinephrine release. In 30 of the 100 vessels studied, there was spontaneous myogenic tone. In these arteries, field stimulation caused frequency- and voltage-dependent relaxations. These responses were neural in origin, dependent on sympathetic nerve activity, but were nonadrenergic and noncholinergic in nature. Naloxone, indomethacin, and substance P inhibited these relaxations with no significant effect on the tone. The opioid agonist, 1–13 dynorphin relaxed these vessels and only naloxone inhibited this response. The effects of these agents were selective against field-stimulated responses since they did not alter the relaxation to the nonspecific agent sodium nitroprusside. These results provide circumstantial evidence for opioid-mediated vascular relaxation that is presynaptically modulated by prostanoids and substance P.
Calmodulin antagonists inhibit dihydropyridine calcium channel activator (BAY-K-8644) induced cGMP synthesis in pituitary tumor cells
Authors: Heisler Seymour
Published: April 2011

The dihydropyridine calcium channel activator, BAY-K-8644, stimulates cGMP formation in ACTH-secreting mouse AtT-20 clonal corticotrophs. The recent report that calmodulin antagonists could inhibit dihydropyridine binding in several tissues suggested that these agents might also affect the cyclic nucleotide response to BAY-K-8644. In fact, TMB-8, trifluoperazine, and melittin, described as in vitro antagonists of calmodulin-dependent enzyme activities, all inhibited BAY-K-8644 induced cGMP synthesis in a concentration-dependent manner. The antagonists had no effect on cGMP formation stimulated by sodium nitroprusside or sodium azide. The calcium channel antagonist, nifedipine, did not stimulate cGMP formation nor did it alter the effect of BAY-K-8644 on accumulation of the nucleotide; one explanation thus is that the cyclase involved in cGMP formation is coupled to a low affinity binding site for BAY-K-8644, which is less accessible to other dihydropyridines. The relation of cyclic GMP formation to the function of the calcium channel in AtT-20 cells remains unknown.
How are we to determine whether dietary interventions do more good than harm to hypertensive patients?
Authors: Sackett David L.
Published: April 2011

This paper categorizes studies of dietary interventions in hypertensive patients into five categories based on the levels of evidence: level I, randomized trials with low false-positive (alpha) and low false-negative (beta) errors (high power); level II, randomized trials with high false-positive (alpha) and (or) high false-negative (beta) errors (low power); level III, nonrandomized concurrent cohort comparisons between contemporaneous patients who did and did not receive a nutritional intervention; level IV, nonrandomized historical cohort comparisons between current patients who did receive a nutritional intervention and former patients (from the same institution or from the literature) who did not; level V, case series without controls.
Plasma lipoprotein cholesterol and triglycerides and lipoprotein lipase activity in epididymal white adipose tissue of rats fed high sucrose or high corn oil diets
Authors: Deshaies Yves
Published: April 2011

The present study was undertaken to compare plasma lipoprotein lipid composition, as well as white adipose tissue lipoprotein lipase activity, in rats fed purified diets high in either sucrose or corn oil. The experimental diets (65% of calories as sucrose or corn oil, 15% as the opposite nutrient, and 20% as casein) were given ad libitum for 4 weeks. An additional group was fed a nonpurified diet as a reference diet. Both sucrose and oil diets were spontaneously consumed in isocaloric amounts by the animals. Despite energy intakes that were 35% lower than that of the reference group, the sucrose and oil groups exhibited final body weights that were only 6 and 9% lower, respectively, than that of the reference group, and accumulated more fat in the epididymal depots. Postprandial as well as fasting total cholesterol levels were similar in the sucrose and oil groups, while the high-density lipoprotein to total cholesterol ratio was highest in the animals fed corn oil. In both the fasted and fed states, plasma total triglyceride levels were 73% higher in the sucrose group than in the corn oil group. The largest triglyceride differences due to diet were observed in the chylomicron + very-low-density lipoprotein fraction. The oil-fed rats accumulated large amounts of triglycerides in their livers. Postprandial lipoprotein lipase activity in epididymal adipose tissue was almost twice as high in the sucrose group as in the oil group. In the fasting state, but not in the fed state, plasma insulin levels correlated negatively with plasma triglycerides and positively with liver triglyceride content, whereas no relationship was observed between insulin and lipoprotein lipase activity in either fasted or fed animals. From the present findings, it appears that the sucrose-induced hypertriglyceridemia was not partly caused by decreased activity of lipoprotein lipase in white adipose tissue. Finally, this study suggests that the level of circulating insulin following intake of sucrose or corn oil may not determine per se the extent of stimulation of white adipose tissue lipoprotein lipase by these nutrients.
The effect of oxidized isoprenaline on the chick embryonic heart
Authors: Janatová T. , Pelouch V. , Oštádal B. , Krause E.G.
Published: April 2011

Intra-amnial administration of isoprenaline (IPRO) to chick embryos induces a number of myocardial lesions. The purpose of the present study was to investigate whether similar changes may also be induced after injection of spontaneously oxidized isoprenaline and commercially obtained adrenochrome. Cardiotoxicity of these substances has been demonstrated in adult animals. IPRO, oxidized IPRO, or adrenochrome were administered intra-amnially to 10-day-old chick embryos at doses of 0.1, 1.0, 10.0, and 100.0 mg∙kg−1. Parallel experimental groups received propranolol at a dose of 1 mg∙kg−1, 15 s before injection of IPRO or oxidized IPRO. The cAMP level in the heart was determined by radioimmunoassay 2 and 30 min after administration of IPRO, oxidized IPRO, or adrenochrome at a single dose of 10.0 mg∙kg−1. It has been found that in embryos the effect of IPRO and oxidized IPRO is dose dependent. The rise in mortality and development of cardiomegaly together with increased hydration and disturbances of the development of coronary vascularization were highly significant starting from the dose of 10 mg∙kg−1. Furthermore, both drugs significantly increased cAMP levels in the embryonic heart. On the other hand, the administration of adrenochrome was without any effect. The changes induced by IPRO were prevented by the administration of the beta-blocking agent propranolol; the lesions induced by spontaneously oxidized IPRO were, however, prevented only partially.
Plasma vasopressin response to haemorrhage in the anaesthetized rabbit
Authors: Rankin A. J. , Kelpin B. G. , Courneya C. A. , Wilson N. , Ledsome J. R.
Published: April 2011

In chloralose–urethane anaesthetized rabbits the acute circulatory and plasma vasopressin (pAVP) responses to moderate haemorrhage of 6 mL/kg body weight (10% blood volume) were followed after serial section of the aortic, vagus, and carotid sinus nerves. With all nerves intact, haemorrhage resulted in significant increases in pAVP, accompanied by decreases in systemic arterial pressure and right atrial pressure. With subsequent section of each afferent nerve, pAVP still increased in response to haemorrhage regardless of the order of nerve section. These results suggest that, in the anaesthetized rabbit, there is a further component of the pAVP response to haemorrhage, in addition to those carried in the aortic, vagus, and carotid sinus nerves.
Effects of fasting and food restriction on brown adipose tissue composition in normal and dystrophic hamsters
Authors: Desautels M. , Dulos R. A. , Yuen H. M.
Published: April 2011

Fasting for 36–48 h or food restriction (30% reduction of daily food intake for 6 weeks) caused brown adipose tissue (BAT) atrophy in hamsters. Fasting-induced atrophy was characterized by reductions in tissue mass, DNA, protein, and thermogenin. By contrast, food restriction had no effect on tissue cellularity (DNA) but markedly reduced the tissue protein and thermogenin contents. The concentration of thermogenin in isolated mitochondria was unchanged by fasting or food restriction. Dystrophic hamsters had a reduced BAT mass when compared with weight-matched control hamsters. This resulted from a reduction in tissue cellularity since BAT DNA, protein and thermogenin contents were all reduced. The extent of binding of [3H]guanosine diphosphate to isolated mitochondria and their content of thermogenin were similar in normal and dystrophic hamsters. In response to cold exposure, as in normal hamsters, BAT of dystrophic hamsters grew and the tissue thermogenin increased, but the mitochondrial concentration of thermogenin did not change. In response to fasting, in contrast with normal hamsters, there was no significant reduction in BAT DNA in dystrophic animals and the loss of tissue protein was reduced. However, the relative changes in BAT composition during chronic food restriction were similar in normal and dystrophic animals. Thus, reduction in hamster BAT thermogenic capacity during food deprivation may occur by loss of cells and (or) reduction in the tissue protein and thermogenin contents. The extent of protein and (or) DNA loss may be dependent upon the original tissue mass and the severity of food deprivation.
Neuronal activity recorded extracellularly in chronically decentralized in situ canine middle cervical ganglia
Authors: Armour J. A.
Published: April 2011

In chronically decentralized in situ middle cervical ganglia of 10 dogs, 279 spontaneously active neurons were identified. One hundred and ten (39%) of these were spontaneously active during specific phases of the cardiac cycle, primarily during systole, and the activity of nearly half of these cardiovascular-related neurons was modified by gentle mechanical distortion of the vena cavae, heart, or thoracic aorta. Another 60 (22%) of the identified neurons had respiratory – related activity, but the activity of only 2 of them was modified by gentle mechanical distortion of pulmonary tissue. Twenty-nine of the other 109 identified neurons were activated by gentle mechanical distortion of localized regions of the neck, ventral thoracic wall, or ventral abdominal wall. Because of the presence of activity in the chronically decentralized middle cervical ganglion, these data infer that some afferent neurons are located in the thoracic autonomic nervous system. Some middle cervical ganglion neurons were activated by single 1–4 ms stimuli delivered to a nerve connected to the ganglion. During repetitive stimuli delivered at 0.5 Hz none were activated after a fixed latency following the stimuli. Many more neurons were activated by 10- to 200-ms trains of 1–4 ms stimuli delivered with interstimulus intervals of 1–10 ms. The majority of these neurons could still be activated electrically after the administration of cholinergic and adrenergic pharmacological blocking agents. As the spontaneously active neurons, as well as those which were not spontaneously active, which were recorded were not consistently activated by single 1–4 ms stimuli delivered individually to every nerve connected to the middle cervical ganglion, they presumably did not project axons into these nerves and thus are presumed not to be afferent or efferent postganglionic neurons but rather to be local circuit neurons. It is concluded that local circuit neurons in the middle cervical ganglion are involved in regulating cardiovascular, respiratory, and other tissues and can function independent of neurons in the central nervous system.
Pentobarbital inhibits hippocampal neurons by increasing potassium conductance
Authors: O'Beirne M. , Gurevich N. , Carlen P. L.
Published: April 2011

The effects of sodium pentobarbital were studied using intracellular recordings from CA1 and CA3 pyramidal cells in slices of guinea pig hippocampus. Drugs were applied either by perfusion or by pressure ejection at concentrations of 10−6, 10−5, and 10−4 M. Pentobarbital at all concentrations caused neuronal hyperpolarization, decreased spontaneous activity, and sometimes decreased input resistance. Hyperpolarization also occurred in zero calcium perfusate or with tetrodotoxin in the perfusate. The postspike train long-lasting afterhyperpolarization, which is an intrinsic calcium-mediated potassium conductance, was increased at all doses. γ-Aminobutyric acid induced depolarizing dendritic responses were augmented only at 10−4 M pentobarbital. It is proposed that one of the important mechanisms of pentobarbital neuronal inhibition, particularly at lower doses, is an increase in potassium conductance.
The role of heme metabolism during the induction of hepatic and renal cytochrome P-450 levels and drug-metabolizing enzymes in rats by a Prudhoe Bay crude oil
Authors: Khan S. , Rahimtula A. D.
Published: April 2011

Administration of Prudhoe Bay crude oil (PBCO) to rats resulted in a dose-related (i) increase in liver weight; (ii) rapid and marked increase in the activity of hepatic δ-aminolevulinate synthetase, the initial and rate-limiting enzyme in the heme biosynthetic pathway; (iii) rapid decline in the activity of hepatic heme oxygenase, the rate-limiting enzyme of heme catabolism; and (iv) more gradual increase in the levels of hepatic cytochrome P-450 and some mixed-function oxidase activities such as benzo[a]pyrene hydroxylase and 7-ethoxyresorufin-O-deethylase. PBCO treatment also increased renal cytochrome P-450 levels and mixed-function oxidase activities; however, δ-aminolevulinate synthetase and heme oxygenase activities were unchanged. This suggests that different regulatory mechanism(s) may be involved in renal heme metabolism and induction of monoxygenase system.
The effect of face fanning during recovery from exercise hyperthermia
Authors: Germain Marc , Jobin Michel , Cabanac Michel
Published: April 2011

Hyperthermia was induced in nine subjects on two separate occasions by a progressive treadmill run, which resulted in an average esophageal temperature (Tes) of 39.77 ± 0.07 °C after 30–57 min. Fanning the face during exercise to simulate conditions during running (wind at 3.75 m∙s−1) maintained a tympanic temperature (Tty) that was lower than Tes; the difference was 1.5 °C at the end of exercise. In one session, face fanning was interrupted at the end of running, whereas in the other it was maintained for 15 min after exercise stopped. Face fanning had no significant influence on the fall of Tes during recovery, but it markedly influenced the course of Tty during this period. When face fanning was stopped at the end of the run, Tty rose by nearly 0.5 °C, peaked after 4.5 min. and thereafter decreased slowly to a value close to Tes. In contrast, when face fanning was maintained throughout the recovery period, Tty rose only slightly (0.1 °C) and remained significantly lower than Tes at all times. The results suggest that following hyperthermic exercise, face fanning could be helpful in preventing acute cerebral hyperthermia.
Cerebral blood flow in intoxicated newborn piglets
Authors: MacIntyre Cara J. , Ong Bill Y. , Sitar Daniel S.
Published: April 2011

Ethanol exposure in the neonatal period causes impaired brain growth and altered adult behaviour in rats. One possible mechanism may be altered cerebral perfusion caused by ethanol intoxication. We assessed the effects of ethanol on cerebral blood flow and its autoregulation in 2-day-old piglets. Piglets received ethanol (1.4 g/kg) or an equivalent volume of dextrose 5% in water over 30 min. One hour later, cerebral blood flow was measured using the microsphere technique at resting, elevated, and decreased mean arterial blood pressure. Ethanol-treated piglets had total cerebral blood flows of 88 ± 14, 82 ± 10, and 82 ± 12 mL∙100 g−1∙min−1 (mean ± SE) at mean arterial blood pressures of 12.4 ± 1.1, 15.7 ± 1.5, and 8.2 ± 0.9 kPa. Corresponding values in control piglets were 82 ± 14, 78 ± 4, and 82 ± 7 mL∙100 g−1∙min−1 at mean arterial blood pressures of 10.5 ± 1.5, 14.0 ± 1.2, and 7.7 ± 1.1 kPa. At resting arterial blood pressures, regional blood flows to basal ganglia, cortex, brainstem, and cerebellum in ethanol-treated piglets were 123 ± 21, 90 ± 16, 94 ± 17, and 77 ± 12 mL∙100 g−1∙min−1, respectively. Corresponding regional blood flows for the control piglets were 118 ± 16, 85 ± 15, 76 ± 16, and 76 ± 16 mL∙100 g−1∙min−1. Blood flow to basal ganglia was greater than to other brain regions in both ethanol-treated and control piglets (P < 0.01). Total and regional blood flows remained unchanged with altered mean arterial blood pressures, indicating normal autoregulation of cerebral blood flow in both ethanol-treated and control piglets.
Latency of transmitter release at crayfish motor nerve endings examined by intracellular depolarization
Authors: Wojtowicz J. M. , Parnas I. , Parnas H. , Atwood H. L.
Published: April 2011

Latency of release of individual quanta of transmitter was studied at neuromuscular junctions of a crayfish (Procambarus clarkii). Postsynaptic quantal currents were recorded at individual motor nerve endings with a macropatch electrode while the subterminal axon branch was depolarized by current passed through an intracellular microelectrode. For depolarizing currents of moderate size, the latency of transmitter release did not change when the duration of the depolarizing current was altered. Previous studies in which a contrary result was obtained may have been compromised by artefacts or by the sampling methods employed. The present results do not support the hypothesis of a depolarization-induced "repressor" of quantal release.
Demonstration of epidermal growth factor binding sites in the adult rat small intestine by autoradiography
Authors: Chabot J.-G. , Walker P. , Pelletier G.
Published: April 2011

The distribution of epidermal growth factor (EGF) receptors was studied in the distal portion of duodenum using light microscopic autoradiography performed at different time intervals (2–60 min) after intravenous injection of 125I-labelled EGF into adult rats. The results revealed a substantial binding of EGF to both cell types of the mucosal epithelium in duodenal crypts and villi, the columnar absorptive cells and the globet cells. Labelling was also found over few cells of lamina propria. No labelling was observed over the striated border of the duodenal mucosa epithelium. The time-course study performed in epithelial cells of duodenal crypts and villi showed that most silver grains were found at the periphery of the cells 2 min after injection. At the 7 min, silver grains were found both at the periphery and over the cytoplasm, more specifically the supranuclear region of the columnar absorptive cells. The number of grains overlying the cytoplasm of these cells was markedly reduced at 60 min. By quantitative autoradiography, maximal values were reached 7 min after the injection. Control experiments indicated that the autoradiography reaction was due to specific interaction of 125I-labelled EGF with its receptor. These results clearly indicate that EGF receptors are present in epithelial cells of the duodenal mucosa and suggest that the radioactive tracer is taken up by these cells.
Effects of a specific bradycardic agent (AQ-A39) and verapamil on β-adrenergic responses in isolated guinea pig atria
Authors: Siegl Peter K. S. , Morgan George
Published: April 2011

AQ-A39 (5,6-dimethoxy-2-{3-[(α-(3,4-dimethoxy)phenylethyl)methylamino]propyl}-phthalimidine), a specific bradycardic agent, and verapamil, a calcium channel blocker, were studied for their ability to alter rate and force of contraction in the presence and absence of isoproterenol, a β-adrenergic stimulant, using isolated guinea pig atria. Both compounds (10−7–10−4 M) produced dose-related decreases in frequency of spontaneously beating right atria. Verapamil decreased, while AQ-A39 increased, the force of contraction of electrically stimulated (1.0 Hz) left atria. At equal negative chronotropic concentrations, AQ-A39 was more effective than verapamil in reducing the maximum isoproterenol-induced tachycardia. Verapamil, but not AQ-A39, antagonized positive inotropic responses to isoproterenol. Therefore, AQ-A39 differed from verapamil in that (i) AQ-A39 was a more selective bradycardic agent in both β-adrenergically stimulated and nonstimulated preparations and (ii) AQ-A39 was more effective in reducing isoproterenol-elevated heart rate compared with basal heart rate. This profile of activities suggests that AQ-A39 will be beneficial in cardiac pathologies where sympathetic nervous system activity is elevated and a lowering of heart rate without a reduction in cardiac contractility is desired.
Mechanism of impaired myogenic response in cerebral blood vessels during posthypoxic recovery
Authors: Mallick B. A. , Bose D. , Chau T. , Ong B. Y.
Published: April 2011

Cerebral blood flow autoregulation is impaired in newborn animals when a brief period of hypoxia is followed by normoxia. Because myogenic mechanisms are widely thought to be responsible for autoregulation, this study examined the effect of hypoxia and reoxygenation on the isometric mechanical function of isolated cerebral (basilar) arterial smooth muscle made to contract rhythmically and thus simulate the behaviour of arterioles. Although at rest a small amount of active tension was present in these preparations, this tension was further increased and the muscle was rendered spontaneously rhythmic by treatment with 4-aminopyridine. Reduction of bath [Formula: see text] from 120 to 25 mmHg (1 mmHg = 133.32 Pa) caused an increase in tension followed by a return towards normal tension. At this time rhythmic oscillations gradually decreased in amplitude. Restoration of normal oxygen tension caused a rapid reduction and an undershoot in tension followed by recovery to normal level. Two possible mechanisms for this undershoot, which may be due to a decrease in myogenic responsiveness and therefore of autoregulatory function, were tested. 8-Phenyltheophylline, an antagonist of adenosine receptors, caused a decrease in the inhibitory mechanical effects of adenosine (10−6–10− M). However, in the presence of 8-phenyltheophylline, there was no change in the undershoot in tension caused by reoxygenation, thus ruling out involvement of adenosine released from the vessel in smooth muscle inhibition due to hypoxia. In a separate series of experiments, the role of an electrogenic sodium pump in causing the undershoot was tested. Treatment with 5-hydroxytryptamine in a K+ -free bathing medium caused an increase in basilar artery tension. When normal potassium concentration was restored the muscle relaxed with a transient undershoot below the basal tension level. In muscle preparations pretreated with ouabain (3 × 10−6 M), the K+-induced undershoot was abolished and replaced by a transient contraction. The same concentration of ouabain decreased by 92% the tension undershoot caused by reoxygenation. These experiments rule out participation of adenosine released from the blood vessel in the loss of myogenic tone during reoxygenation. The data also indicate that reactivation of the sodium pump may be responsible to some extent for the undershoot in tone during reoxygenation of isolated canine basilar artery.
Methylamine does not inhibit rates of endogenous lipolysis in isolated myocardial cells from rat heart
Authors: Kryski Jr. Albert , Larsen Terje S. , Ramírez Ignasi , Severson David L.
Published: April 2011

Triacylglycerol lipase activity with a pH optimum of 5 was present in homogenates of myocardial cells from rat heart. Acid lipase activity was inhibited by serum, heparin, and increased ionic strength. Methylamine, a lysosomotropic agent, did not inhibit the basal or isoproterenol-stimulated rate of endogenous lipolysis as measured by glycerol output from control myocytes. Similarly, accelerated rates of glycerol output that are a consequence of an elevation in the intracellular stores of triacylglycerols in myocytes from diabetic rat hearts and from myocytes prepared with free fatty acids in the isolation solutions were not reduced by methylamine. Therefore, the acid lysosomal triacylglycerol lipase must not be involved in the mobilization of endogenous triacylglycerols in myocardial cells from rat heart.
Effect of cold exposure on energy metabolism in the young pig
Authors: Herpin Patrick R. , McBride Brian W. , Bayley Henry S.
Published: April 2011

Twenty-four piglets were weaned at 3 weeks of age and received 615 kJ metabolizable energy/(kg body weight-day). The temperature was reduced from 29 to 25 °C by 4 weeks of age. Six pigs were exposed to cold by reducing the temperature to 10 °C by 5 weeks of age while the other six were exposed to 23 °C. These two temperatures were maintained for 3 weeks. Each week the three pigs closest to the mean weight of each group were used for measurements of heat production for 23 h by open-circuit calorimetry and glucose turnover by continuous infusion of [6-3H]- and [U-14C]-glucose. The animals were sacrificed at 8 weeks of age, a sample of their intercostal muscle was used for in vitro measurement of muscle respiration, and the carcass was analyzed. There was no change in heat production, glucose turnover, and rectal temperature during the 3 weeks of cold exposure, so the data were pooled. Cold exposure increased heat production by 50%, forced mobilization of fat reserves (1000 g over the 3 weeks), and increased glucose replacement rate by 20%. The decline in rectal temperature to 37.6 from 38.8 °C could be regarded as a strategy to reduce energy needed to regulate body temperature. In the cold, heat production equalled metabolizable energy intake, but protein deposition was maintained at the same level as that in the pigs at the thermoneutral temperature, using the energy derived from the mobilization of body fat. The increase in Na+–K4 ATPase dependent respiration accounted for 70% of the increase in O2 consumption of muscle from cold-exposed pigs and thus is potentially an important component of cold-induced thermogenesis in the pig.
Characterization of the triacylglycerol lipase activity in three types of rat skeletal muscle
Authors: Miller Wayne C. , Palmer Warren K. , Arnall David A. , Oscai Lawrence B.
Published: April 2011

The purpose of this study was to characterize the lipolytic activity of the alkaline triglyceride lipase in homogenates of three types of skeletal muscle obtained from heparin-perfused rat hindlimb. Specifically, the red portion of the vastus lateralis, the white portion of the vastus lateralis, and the soleus muscles were examined. To remove capillary-bound lipoprotein lipase from the capillary beds, muscle was perfused with an erythrocyte-free buffer containing 4% albumin, 5 units of heparin/mL, and 7.5 μM adenosine. Adenosine reduced perfusion pressure from 117 ± 5 to 86 ± 6 mmHg (1 mmHg = 133.32 Pa), providing evidence for an effective vasodilation. This vasodilation increased the amount of lipoprotein lipase removed from the capillary beds. By the end of the experiment, perfusates were lipoprotein lipase-free. Oxygen supply to the perfused hindlimb appeared adequate as evidenced by similar high energy phosphate values for perfused and contralateral control tissues. For example, in soleus muscle, ATP content was 4.5 ± 0.6 vs. 4.2 ± 0.3 μmol/g, ADP concentration was 1.0 ± 0.2 vs. 1.4 ± 0.2 μmol/g, and creatine phosphate level was 12.9 ± 0.7 vs. 11.0 ± 0.6 μmol/g for perfused and contralateral control soleus, respectively. In addition, K+ output by the hindlimb was negligible, while glycolytic flux of perfused muscle was similar to that measured in control tissue. The findings that triglyceride levels of soleus and red vastus lateralis were decreased suggest that endogenous triglyceride was providing energy for the hindlimb during perfusion. Skeletal muscle triglyceride lipase activity was stimulated by serum and heparin, inhibited by NaCl and protamine, and had a pH optimum of 8.1. These results are consistent with the hypothesis that the major lipolytic activity present in the intracellular compartment of skeletal muscle is the alkaline triglyceride lipase with characteristics similar to those of lipoprotein lipase.
Transfer of newly made triglyceride from hepatocytes to preexisting extracellular very low density lipoproteins
Authors: Yoshino Gen , Steiner George
Published: April 2011

Previous in vivo studies suggested a new model to describe the metabolism of very low density lipoproteins (VLDL). It was hypothesized that some of the lipoprotein triglyceride was transferred directly from hepatocytes and intestinal mucosal cells into preexisting extracellular VLDL particles. These studies employ an in vitro system to test this hypothesis. Isolated rat liver cells containing newly made radioactive triglyceride were prepared. These cells were incubated in medium to which exogenous VLDL had or had not been added. The presence of extracellular VLDL (rat or human) stimulated the transfer of labeled triglyceride out of the liver cells. This triglyceride was recovered in the medium's VLDL (as determined by its density and its precipitability by MnCl2–heparin or by anti-apoprotein B). Although these studies focussed on VLDL, preliminary data showed that similar triglyceride transfer occurred in the presence of the other apoprotein B containing lipoprotein, low density lipoprotein (LDL). However, in the presence of equivalent amounts of LDL, this triglyceride transfer was less than that seen in the presence of exogenous VLDL. Furthermore, the increased triglyceride released in the presence of LDL occurred entirely in the d < 1.006 fraction of the medium. That released in the presence of VLDL was recovered in the d > 1.006 fraction. Hence, we conclude that the transfer of the newly made triglyceride was from the cell to the extracellular lipoprotein that had been added to the medium. The transfer of triglyceride to VLDL did not depend on the synthesis and release of new VLDL particles because it was not accompanied by a change in the production of [14C]leucine VLDL protein, it was not blocked by chloroquine, and the LDL induced triglyceride release occurred into the d > 1.006 fraction. This transfer did not depend on the previously described triglyceride-transfer factor. The present in vitro studies support the model suggested by our earlier in vivo studies. The VLDL particle does not appear to be metabolized as a complete intact unit. Rather, some of its major lipid component, triglyceride, can move directly into and out of already existing extracellular lipoproteins.
Effect of transient neonatal hypothyroidism on the free aspartic acid, glutamic acid, and GABA content of different central auditory regions in the rat
Authors: Hébert Réal , Poulin Richard , Barden Nicholas , Dussault Jean H.
Published: April 2011

The aspartic acid, glutamic acid, and γ-aminobutyric acid (GABA) contents were determined in four central auditory system regions in rats with transient neonatal hypothyroidism compared with control ones: the ventral and dorsal parts of the cochlear nucleus, the central nucleus of the inferior colliculus, the auditory cortex, and in an extra-auditory structure, the substantia nigra pars reticulata. The animals were sacrificed at 50 days of age, brain tissue samples were taken out by microdissection, and the free amino acids were extracted. The amino acid content was assessed by double-isotope labelling following two-dimensional thin-layer chromatogaphy separation. GABA content was significantly decreased in both cochlear nucleus regions and glutamic acid was elevated in the inferior colliculus. Neonatal hypothyroidism had no significant effect on the aspartic acid levels in the regions studied. The results suggest an effect of neonatal hypothyroidism on regional contents of free amino acids known as candidate neurotransmitters in the auditory system.
Calcium and vitamin D modulate mouse colon epithelial proliferation and growth characteristics of a human colon tumor cell line
Authors: Wargovich M. J. , Lointier P. H.
Published: April 2011

The role of calcium and vitamin D in the prevention of colorectal cancer is only now being investigated at the organismal, cellular, and molecular biologic levels. Recent epidemiologic studies have supported the hypothesis that dietary calcium and vitamin D may be related to a reduced risk for colon cancer. The evidence from laboratory investigations in animals and in cell culture also indicate a possible preventative effect. Addition of calcium and vitamin D to the roster of developmental cancer chemopreventative agents for further research is warranted.
Cycloheximide blocks insulin-like growth factor I but not somatostatin inhibition of growth hormone secretion
Authors: Sheppard M. S. , Bala R. M.
Published: April 2011

Growth hormone secretion is controlled by the two hypothalamic hormones, growth hormone releasing factor (GRF) and somatostatin. In addition, the insulin-like growth factors (IGF or somatomedins) which are themselves growth hormone dependent, inhibit growth hormone release in vitro, therefore acting to close the negative feedback loop. The studies reported here examine some of the differences between inhibition of growth hormone secretion by somatostatin and IGF-I in vitro. The major finding is that cycloheximide, a protein synthesis inhibitor, blocks inhibition of GRF-stimulated growth hormone release caused by IGF-I, without changing the inhibition caused by somatostatin. The experiments were done by exposing mixed rat adenohypophysial cells to secretagogues with or without cycloheximide for 24 h in a short term culture. Somatostatin (0.6 nM) totally blocked rat GRF (1 nM) stimulated growth hormone release to values 48% of control (nonstimulated values), while IGF-1 (27 nM) only reduced the GRF-stimulated growth hormone release by 27 ± 3% (N = 5). Cycloheximide (15 μg/mL) totally blocked the effect of IGF-I but not somatostatin. A low concentration (0.12 nM) of somatostatin, which only partly inhibited growth hormone release, was also unaffected by cycloheximide. In purified rat somatotrophs, somatostatin (0.1 nM) inhibited GRF-stimulated cAMP levels slightly and reduced growth hormone release while IGF-I (40 nM) had no effect. We suggest that IGF-I inhibits only the secretion of newly synthesized growth hormone, while somatostatin inhibits both stored and newly synthesized growth hormone pools.
Coronary circulatory pressure gradients
Authors: Klassen Gerald A. , Armour J. Andrew , Garner J. Barry
Published: April 2011

The pressure gradients of the canine coronary circulation were measured in 37 dogs during control and following eight interventions: left stellate ganglion or left vagosympathetic trunk stimulation, as well as isoproterenol, acetylcholine, noradrenaline, adenosine, phenylephrine, or adrenaline infusions. During control, pressure gradients in the epicardial coronary arteries (measured from the aorta to coronary artery branch) were 15.2 ± 1 mmHg(1 mmHg = 133.32 Pa) during systole and 10.6 ± 1.5 mmHg during diastole. Adrenaline increased this systolic gradient, while acetylcholine and phenylephrine decreased it. In contrast, the pressure gradients in the small coronary arteries (from the branch of an epicardial artery to the pressure in an obstructed coronary artery) were 56 ± 1.3 mmHg during systole and 63.7 ± 1.3 mmHg during diastole. These gradients were increased by phenylephrine during both systole and diastole, noradrenaline and adrenaline during diastole and decreased by isoproterenol (systolic), left vagosympathetic trunk stimulation (diastolic), acetylcholine (systolic and diastolic), and adrenosine (diastolic). The microcirculation and small vein gradients during control were 16.4 ± 1.2 mmHg during systole and 8.5 ± 0.8 mmHg during diastole. Decreases in this gradient were produced by isoproterenol, acetylcholine, and adenosine during systole and adenosine during diastole. These observations are consistent with the concept that the coronary circulation has considerable regulatory capacity in all of its component parts. Specifically, epicardial arteries appear to function as both conduits and as resistance vessels, small arteries as major resistance vessels, and the microcirculation and small veins as both capacitors and resistors.
The release of catecholamines from the adrenal medulla and its modulation by α2-adrenoceptors in the anaesthetized dog
Authors: Foucart Sylvain , Nadeau Réginald , Champlain Jacques de
Published: April 2011

The adrenal nerve of anaesthetized and vagotomized dogs was electrically stimulated (10 V pulses of 2 ms duration for 10 min) at frequencies of 1, 3, 10, and 25 Hz. There was a correlation between the frequency of stimulation and the plasma concentrations of epinephrine, norepinephrine, and dopamine in the adrenal vein, mainly after the 1st min of stimulation and the maximal concentration was reached sooner with higher frequencies of stimulation. Moreover, the relative percentage of catecholamines released in response to the electrical stimulation was not changed by the frequency of stimulation. To test the hypothesis that a local negative feedback mechanism mediated by α2-adrenoceptors exists in the adrenal medulla, the effects of the systemic administration of clonidine (α2-agonist) and yohimbine (α2-antagonist) on the concentrations of catecholamines in the adrenal vein were evaluated during the electrical stimulation of the adrenal nerve (5 V pulses of 2 ms duration for 3 min) at 3 Hz. Moreover, the effects of the systemic injections of more specific α2-agonist and antagonist (oxymetazoline and idazoxan) were tested on the release of catecholamines in the adrenal vein in response to electrical stimulation of the splanchnic nerve at 1 and 3 Hz frequencies. The injection of 0.5 mg/kg of yohimbine caused a significant increase in the concentrations of epinephrine and norepinephrine in the adrenal vein induced by the electrical stimulation of the adrenal nerve and the injection of 15 μg/kg of clonidine had no effects. In the second series of experiments, the injection of 2 μg/kg of oxymetazoline caused a significant decrease in the release of epinephrine and norepinephrine at 1 Hz, but similarly to clonidine, there were no changes at 3 Hz. In contrast, the release of epinephrine and dopamine in response to electrical stimulation of the splanchnic nerve was increased at 3 Hz after the injection of idazoxan, but not at 1 Hz. It is concluded that the adrenal medulla catecholamines secretion appears to be partly modulated by a presynaptic inhibitory mechanism that involves α2-adrenoceptors. The observation that agonists appear to be more efficient at low frequencies of stimulation while antagonists appear to be more efficient at higher frequencies could be explained by the possibility that adrenal medullary α2-receptors would be saturated at higher frequencies of stimulation.
Effect of chronic estrogen on the skin temperature response to naloxone in morphine-dependent rats
Authors: Katovich Michael J. , O'Meara June
Published: April 2011

It is well documented that opioids and sex steroids modify body temperature in the rat. We have previously reported that the temperature responses to naloxone in the morphine-dependent rat was more pronounced in the female than in the male rat. In addition, ovariectomy but not castration resulted in altered temperature responses in the morphine-dependent rat, which suggests a role for estrogen in modifying the temperature responses. This study was designed to evaluate the effect of sex steroid hormones on the surge in tail skin temperature associated with administration of naloxone to morphine-dependent female rats. Ovariectomized female rats were treated with estrogen (0.5 mg pellet), progesterone (5 mg pellet), or the combined therapy for 21 days. Administration of naloxone to these morphine-dependent rats resulted in a 5.9 ± 0.5 °C rise in tail skin temperature in the placebo control rats and 5.7 ± 0.5 °C in the progesterone-treated group; however, there was a significantly reduced elevation in tail skin temperature of 3.1 ± 1.0 °C and 2.9 ± 1.0 °C in the estrogen and estrogen–progesterone treated groups. Body weights also were significantly depressed in the estrogen-treated groups. In a subsequent study, the effects of several doses of chronic estrogen treatment were evaluated (0.1–50 mg pellets). The elevation of tail skin temperature in response to administration of naloxone to morphine-dependent rats was significantly reduced at all doses of estrogen when compared with placebo-treated controls. The degree of attenuation of the surge in tail skin temperature and the increases in uterine and anterior pituitary weights were similar in all five estrogen-treated groups despite the wide range of serum estrogen levels observed. The only apparent dose–response effect observed with the five levels of estrogen treatment was the reduction of body weight. Collectively, these results suggest that chronic estrogen, and not progesterone, replacement attenuates the rise in tail skin temperature observed in the morphine-dependent rat following administration of naloxone.
The role of calcium at the sarcolemma in the control of myocardial contractility
Authors: Langer G. A.
Published: April 2011

The importance of sarcolemmal-bound calcium (Ca) in the control of contraction in mammalian myocardium is indicated by the following results. The curve that relates [Ca]o (from 50 μM to 10 mM) to force development and that which relates [Ca]o to Ca bound to a highly purified sarcolemmal fraction are superimposable. The ability of a series of cations to uncouple excitation from contraction is the same as their relative ability to displace Ca from the sarcolemma. Dimethonium, which specifically displaces cation from the diffuse double layer of the cellular surface, has little effect on contractile force. This indicates that the Ca actually bound to the sarcolemma is the surface Ca important in contractile control. Polymyxin B, a highly charged cationic amphiphilic peptidolipid, specifically competes for Ca-binding sites on anionic and zwitterionic phospholipid. It is a potent displacer of Ca from myocardial cells and purified sarcolemma and a potent uncoupler. Phospholipase D cleaves the nitrogenous base from sarcolemmal phospholipid with production of anionic phosphatide acid. Phospholipase D treatment increases Ca bound to cells and purified sarcolemma and increases force development of ventricular tissue from both neonatal rat and adult rabbit. Insertion of charged amphiphiles in the sarcolemma as phospholipid analogues modulate interaction of Ca with the sarcolemma, e.g., anionic dodecylsulfate increases Ca bound to sarcolemmal vesicles by more than 80% and increases force development in rabbit papillary muscle by 100%. The effect of pH variation on Ca binding to phospholipid extracted from sarcolemma indicates that phospholipid accounts for at least 75% of the binding. The current model proposes a two-site control of Ca binding. One site, with pK in 6.0–7.0 range, controls access of Ca to a second site on phospholipid to which Ca binds. The access controlling sites may be amine groups; the binding sites are likely phosphate and (or) carboxyl groups.
Mechanisms of stimulated 45Ca efflux in skinned skeletal muscle fibers
Authors: Stephenson Elizabeth W.
Published: April 2011

Excitation–contraction (E–C) coupling in skeletal muscle can be studied in skinned fibers by direct assay of 45Ca efflux and simultaneous isometric force, under controlled conditions. Recent work provides evidence that such studies can address major current questions about the mechanisms of signal transmission between transverse tubules and sarcoplasmic reticulum and sarcoplasmic reticulum calcium release, as well as operation of the sarcoplasmic reticulum active Ca transport system in situ. Stimulation by imposed ion gradients at constant [K+][Cl−] product results in 45Ca release with two components: a large Ca2+-dependent efflux, responsible for contractile activation, and a small Ca2+-insensitive efflux. The Ca2+-insensitive stimulation is sustained, consistent with sustained depolarization, and appears to gradate the Ca2+-dependent stimulation; this component is likely to reflect intermediate steps in E–C coupling. Several lines of evidence suggest that the depolarizing stimulus acts on the transverse tubules. It is inhibited by the impermeant glycoside ouabain applied before skinning, which should specifically inhibit polarization of subsequently sealed transverse tubules. Sealed polarized transverse tubules also are the only plausible target for stimulation of 45Ca release by monensin and gramicidin D, which can rapidly dissipate Na+ and K+ gradients; a protonophore and the K+-specific ionophore valinomycin are ineffective, lonophore stimulation is prevented by the permeant glycoside digitoxin; it is also highly Ca2+ dependent. Stimulation of 45Ca release by imposed ion gradients is potentiated by perchlorate, which potentiates charge movements and activation in intact fibers, and is inhibited selectively in highly stretched fibers, presumably by transverse tubule – sarcoplasmic reticulum uncoupling. These results relate the Ca2+-dependent sarcoplasmic reticulum efflux channel to the physiological transverse tubule – sarcoplasmic reticulum coupling pathway, which also could involve Ca2+.
The effects of isoproterenol, UDCG 115, and caffeine on the heat related to excitation–contraction coupling in heart muscle
Authors: Blanchard Edward M. , Alpert Norman R.
Published: April 2011

A myothermal technique was used to measure initial heat and tension independent heat from isometrically contracting papillary muscles taken from the right ventricle of rabbits. Tension independent heat produced by the muscle at Lo was isolated with a 2,3-butanedione monoxime (diacetyl monoxime) – hyperosmotic Krebs solution. The effects of the inotropic drugs isoproterenol (1 × 10−7 M), UDCG 115 (2 × 10−4M), and caffeine (2 × 10−3 M) on heat and mechanical output were measured. We tested the hypothesis that these drugs alter peak twitch tension by increasing the total amount of Ca2+ cycled during the twitch, assuming that net tension independent heat is proportional to total Ca2+ cycled. The hypothesis was rejected for each drug as the positive inotropic effects of isoproterenol and UDCG 115 on twitch tension were not accompanied by increases in net tension independent heat. Net tension independent heat was actually depressed by UDCG 115. The negative inotropic effect of caffeine on twitch tension was accompanied by an increase in tension independent heat at times between the end of mechanical relaxation and the next stimulus. Possible mechanisms to account for these results are discussed.