Canadian Journal of Physiology and Pharmacology
Công bố khoa học tiêu biểu
* Dữ liệu chỉ mang tính chất tham khảo
Sắp xếp:
The antiadrenergic effect of cyclopentyladenosine on myocardial contractility is reduced in vivo in diabetic rats The aim of this study was to test the hypothesis that the antiadrenergic action of adenosine is reduced in diabetes. This was determined by evaluating the effect of experimental diabetes mellitus on the in vivo myocardial antiadrenergic action of cyclopentyladenosine, an adenosine A1 - receptor agonist. Changes in heart rate and ventricular performance in response to infusion of dobutamine, a β1 -adrenergic agonist, were determined in the absence and presence of cyclopentyladenosine, in anesthetized, 10- to 12-week male diabetic (60 mg/kg streptozotocin), insulin-treated diabetic and control rats. Intravenous dobutamine (16 μg/kg) increased +dP/dtmax and −dP/dtmax in control rats from 7 706 ± 553 and 5 449 ± 403 mmHg/s (1 mmHg = 133.3 Pa) to 19 170 ± 465 and 8 855 ± 317 mmHg/s, respectively. In diabetic rats dobutamine increased +dP/dtmax and −dP/dtmax from 5 733 ± 541 and 4 016 ± 426 to 15 015 ± 1 521 and 7 039 ± 809 mmHg/s, respectively. Cyclopentyladenosine significantly attenuated dobutamine-stimulated increases in +dP/dtmax and −dP/dtmax in both control and diabetic rats in a dose-dependent (0.1–3.0 μg/kg) manner. Cyclopentyladenosine potency to attenuate dobutamine-enhanced +dP/dtmax was reduced significantly (p < 0.05) in diabetic rats compared with controls (ID50 , 1.07 vs. 0.59 μg/kg, respectively) with no change in efficacy. The magnitude of cyclopentyladenosine inhibition of dobutamine-enhanced −dP/dtmax was greater in control than diabetic rats (81 vs. 54%, respectively), but ID50 values were not different. Insulin treatment of diabetic rats prevented the observed changes. These data suggest that the antiadrenergic action of adenosine is compromised in diabetes and that this may contribute to the development of diabetic cardiomyopathy.Key words: adenosine, dobutamine, ventricle, left ventricular pressure, streptozotocin.
Canadian Journal of Physiology and Pharmacology - Tập 72 Số 10 - Trang 1245-1251 - 1994
Actions of excitatory amino acids on mesencephalic trigeminal neurons Mesencephalic trigeminal (MeV) neurons are primary sensory neurons of which the cell soma is located within the brainstem, and is associated with synaptic contacts. In previous studies it has been reported that these cells are resistant to kainic acid excitotoxicity, and have little or no responsiveness to exogenously applied glutamate or selective agonists. In an in vitro slice preparation with intracellular recording, we have found that these cells respond to pressure-applied glutamate, N-methyl-D-aspartic acid (NMDA), kainate (KA), and (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). The kainate and AMPA responses appear to be mediated by different receptors, at least in part, since they exhibit differing sensitivity to an AMPA receptor selective antagonist. The agonists generally evoke larger responses than glutamate and exhibit a long-duration desensitization requiring approximately 10 min for full recovery. Some cross-desensitization between the glutamate agonists is also observed. Mesencephalic trigeminal neurons exhibit high-frequency oscillatory activity during depolarizations that approach threshold potentials, and these could combine with transmitter-induced depolarizations to enhance the excitability of these cells. Previous reports of nonsensitivity to glutamate and to kainate excitotoxicity are attributable to relatively small responses, and to the desensitization expressed by these neurons.Key words: mesencephalic trigeminal neurons, glutamate, kainate, AMPA, oscillations, desensitization.
Canadian Journal of Physiology and Pharmacology - Tập 76 Số 9 - Trang 900-908 - 1998
Vanadium exposure enhances lipid peroxidation in the kidney of rats and mice Vanadium (V) as sodium orthovanadate induces an increase in lipid peroxidation in the kidneys after a single subcutaneous or intraperitoneal injection to rats or mice. The rate of malondialdehyde (MDA) formation, an index of lipid peroxidation, by-kidney homogenates increased by more than 100% 1 h after injection. Chronic exposure of rats to vanadium sulfate, initially through maternal milk and later in the drinking water, resulted after 10 weeks in a significant increase in MDA formation by kidney but not by other tissues, in both acute and chronic studies in rats and mice, no significant increase in lipid peroxidation by V treatment was detected in brain, heart, lung, spleen, or liver. In mice, administration of ascorbate prior to acute exposure to V diminished both toxicity, i.e., respiratory depression and limb paralysis, and the formation of MDA in kidney.
Canadian Journal of Physiology and Pharmacology - Tập 63 Số 3 - Trang 196-199 - 1985
The gut as a potential trigger of exercise-induced inflammatory responses Multiple lines of evidence support the hypothesis that ischemia-induced impairment of normal gut barrier function, with loss of the normal tonic counterinflammatory influence of the gut immune system, contributes to the expression of uncontrolled inflammation in critically ill victims of trauma and overwhelming infection. The clinical syndrome known as the systemic inflammatory response syndrome (SIRS), which embodies uncontrolled inflammation in trauma and sepsis, is reproduced in its entirety by vigourous exercise, raising the possibility that the gut may also play a role in exercise-induced inflammation. Both strenuous exercise and systemic sepsis result in impairment of the normal gut barrier to luminal microorganisms, and result in elevated circulating levels of bacterial endotoxin. Under normal circumstances, the immune tissues of the gut-liver axis inhibit the expression of a host response to foodstuffs in the gut lumen, or to the indigenous microbial flora of the gut wall. This influence is an active, energy-requiring process. Both strenuous exercise and critical illness are associated with gut ischemia, providing a common biologic basis for the initiation of a dysregulated inflammatory response. Although direct evidence supporting or refuting the hypothesis that the gut can serve as a trigger for systemic inflammation following strenuous exercise is sparse, the similarities in the clinical manifestations of SIRS and exercise, and the promising results of prophylactic or therapeutic gut-directed strategies in critical illness, suggest that similar approaches may provide benefit for individuals engaged in extreme physical exercise.Key words: sepsis, exercise, endotoxin, gastrointestinal immunity, inflammation.
Canadian Journal of Physiology and Pharmacology - Tập 76 Số 5 - Trang 479-484 - 1998
Characterization of Ca<sup>2+</sup>release from heterogeneous Ca<sup>2+</sup>stores in sarcoplasmic reticulum isolated from arterial and gastric smooth muscle Ca2+ transport was investigated in vesicles of sarcoplasmic reticulum subfractionated from bovine main pulmonary artery and porcine gastric antrum using digitonin binding and zonal density gradient centrifugation. Gradient fractions recovered at 1533% sucrose were studied as the sarcoplasmic reticulum component using Fluo-3 fluorescence or45 Ca2+ Millipore filtration. Thapsigargin blocked active Ca2+ uptake and induced a slow Ca2+ release from actively loaded vesicles. Unidirectional45 Ca2+ efflux from passively loaded vesicles showed multicompartmental kinetics. The time course of an initial fast component could not be quantitatively measured with the sampling method. The slow release had a half-time of several minutes. Both components were inhibited by 20 μM ruthenium red and 10 mM Mg2+ . Caffeine, inositol 1,4,5-trisphosphate, ATP, and diltiazem accelerated the slow component. A Ca2+ release component activated by ryanodine or cyclic adenosine diphosphate ribose was resolved with Fluo-3. Comparison of tissue responses showed that the fast Ca2+ release was significantly smaller and more sensitive to inhibition by Mg2+ and ruthenium red in arterial vesicles. They released more Ca2+ in response to inositol 1,4,5-trisphosphate and were more sensitive to activation by cyclic adenosine diphosphate ribose. Ryanodine and caffeine, in contrast, were more effective in gastric antrum. In each tissue, the fraction of the Ca+2 store released by sequential application of caffeine and inositol 1,4,5-trisphosphate depended on the order applied and was additive. The results indicate that sarcoplasmic reticulum purified from arterial and gastric smooth muscle represents vesicle subpopulations that retain functional Ca2+ channels that reflect tissue-specific pharmacological modulation. The relationship of these differences to physiological responses has not been determined.Key words: calcium channels, smooth muscle, sarcoplasmic reticulum.
Canadian Journal of Physiology and Pharmacology - Tập 80 Số 6 - Trang 588-603 - 2002
The effect of prior exercise and caffeine ingestion on metabolic rate and hormones in young adult males 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.
Canadian Journal of Physiology and Pharmacology - Tập 67 Số 1 - Trang 10-16 - 1989
A radiotracer method for the measurement of central nervous system catecholamines <i>in vivo</i> A new strategy for measurement of brain catecholamines was tested in an animal model. [3 H]Norepinephrine was infused intravenously in rabbits to label the peripheral norepinephrine pools. The specific activity of urinary 3-methoxy-4-hydroxymandelic acid was consistently higher than that for 3-methoxy-4-hydroxyphenylglycol (MHPG). Central sympathectomy with 6-hydroxydopamine abolished this difference. Using the formula we propose, it is estimated that 30–50% of urinary MHPG originates from the central nervous system.
Canadian Journal of Physiology and Pharmacology - Tập 56 Số 3 - Trang 535-538 - 1978
A comparative study of the inhibition of hepatic aldehyde dehydrogenases in the rat by methyltetrazolethiol, calcium carbimide, and disulfiram Methyltetrazolethiol (1-methyl-5-mercapto-1,2,3,4-tetrazole, MTT) is a heterocyclic substituent of the cephalosporin antibiotics, cefamandole, cefoperazone, and moxalactam. Pretreatment of rats with MTT has been reported to increase blood acetaldehyde concentration after ethanol administration. The time course of MTT-induced inhibition of hepatic aldehyde dehydrogenases (ALDH) was determined in adult, male Sprague–Dawley rats in comparison with the hepatic ALDH inhibition induced by calcium carbimide (calcium cyanamide, CC) and disulfiram (D). The apparent onset of maximal inhibition of hepatic low Km ALDH occurred at 2 h for 50 mg/kg MTT (subcutaneous, s.c.) and 7 mg/kg CC (oral) and at 24 h for 300 mg/kg D (oral). The relative magnitude of maximal inhibition of low Km ALDH was CC > D > MTT. The relative duration of enzyme inhibition was D > MTT > CC. High Km ALDH was only inhibited by CC. Hepatic low Km ALDH was selectively inhibited by s.c. and oral administration of 125 mg/kg MTT. For s.c. administration of 125 mg/kg MTT, the magnitude of maximal enzyme inhibition and the duration of inhibition were greater than for the 50 mg/kg dose. Oral administration of 125 mg/kg MTT produced similar inhibition of hepatic low Km ALDH compared with s.c. administration of the same dose. The time course of blood ethanol and acetaldehyde concentrations was determined for the intravenous infusion of two 0.3-g/kg doses of ethanol to rats that were pretreated orally with saline (1 h), MTT (125 mg/kg, 2 h), or CC (7 mg/kg, 1 h). The relative increase in blood acetaldehyde concentration compared with saline pretreatment was CC > MTT. The elimination of ethanol from blood was slower in the MTT- and CC-pretreated animals, and this effect was more pronounced for CC pretreatment. Overall, the data demonstrate that the characteristics of hepatic ALDH inhibition for MTT are different from those of the known ALDH inhibitors, CC and D.
Canadian Journal of Physiology and Pharmacology - Tập 63 Số 5 - Trang 438-443 - 1985
Inhibition of hepatic aldehyde dehydrogenases in the rat by calcium carbimide (calcium cyanamide) Oral administration of 7.0 mg/kg calcium carbimide (calcium cyanamide, CC) to the rat produced differential inhibition of hepatic aldehyde dehydrogenase (ALDH) isozymes, as indicated by the time-course profiles of enzyme activity. The low-Km mitochondrial ALDH was most susceptible to inhibition following CC administration, with complete inhibition occurring at 0.5 h and return to control activity at 96 h. The low-Km cytosolic and high-Km mitochondrial, cytosolic, and microsomal ALDH isozymes were inhibited to a lesser degree and (or) for a shorter duration compared with the mitochondrial low-Km enzyme. The time course of carbimide, the hydrolytic product of CC, was determined in plasma following oral administration of 7.0 mg/kg CC to the rat. The maximum plasma carbimide concentration (102 ng/mL) occurred at 1 h and the apparent elimination half-life in plasma was 1.5 h. Carbimide was not measurable in the liver during the 6.5 h time interval when carbimide was present in the plasma. There were negative, linear correlations between plasma carbimide concentration and hepatic low-Km mitochondrial, low-Km cytosolic, and high-Km microsomal ALDH activities. In vitro studies demonstrated that carbimide, at concentrations obtained in plasma following oral CC administration, produced only 19% inhibition of low-Km mitochondrial ALDH and no inhibition of low-Km cytosolic and high-Km microsomal ALDH isozymes. These data demonstrate that carbimide, itself, is not primarily responsible for hepatic ALDH inhibition in vivo following oral CC administration. It would appear that carbimide must undergo metabolic conversion in vivo to inhibit hepatic ALDH enzymes, which is supported by the observation of no measurable carbimide in the liver when ALDH was maximally inhibited following oral CC administration.
Canadian Journal of Physiology and Pharmacology - Tập 61 Số 9 - Trang 1025-1034 - 1983
A MODIFIED METHOD FOR THE COLORIMETRIC DETERMINATION OF HEPARIN A sensitive accurate quantitative colorimetric assay for heparin with Azure A using the Beckman DK-2 spectrophotometer is described. Limits for the presence of impurities and precautions are given.
Canadian Journal of Physiology and Pharmacology - Tập 45 Số 5 - Trang 787-794 - 1967
Tổng số: 93
- 1
- 2
- 3
- 4
- 5
- 6
- 10