bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of EGTA on vascular smooth muscle contractility in calcium-free medium
Authors: Guan Y. Y. , Kwan C. Y. , Daniel E. E.
Published: April 2011

The effect of EGTA, commonly present in Ca2+-free physiological saline solution, on the contractile responses induced by Ca2+ and phenylephrine was studied in dog mesenteric arteries and aortas of rats and rabbits. EGTA substantially enhanced the contractile responses of these vascular strips or rings to added Ca2+ after a prolonged preincubation period in the Ca2+-free medium. The maximal level of the enhanced contractile responses was independent of EGTA concentration, but the rate of the maximal responses was faster at higher EGTA concentration, presumably as a result of faster removal of intracellular Ca2+. Such a Ca2+-induced response was sensitive to the Ca2+ antagonist, nifedipine. EGTA present at low concentrations (50 and 400 μM) in Ca2+-free medium also inhibited the phenylephrine-induced contractile response more prominently for the longer preincubation periods of the vascular tissues in Ca2+-free medium. Our results suggest that EGTA, even when added at low concentrations to the vascular smooth muscle for a sufficiently long period in a Ca2+-free medium, may cause destabilization of the cell membranes leading to increased permeability to subsequently added Ca2+. EGTA may also remove the superficially bound Ca2+ and subsequently reduce the intracellular Ca2+ pool via extraction of the intracellular Ca2+ at the cell membrane surfaces.
Kainic acid lesions of the median preoptic nucleus: effects on angiotensin II induced drinking and pressor responses in the conscious rat
Authors: Jones D. L.
Published: April 2011

Input to the nucleus medianus of the preoptic region has been suggested to be involved in both the drinking and pressor responses elicited by the central administration of angiotensin II. Evidence in support of this suggestion has been gained principally from electrical lesion experiments. This lesion procedure does not differentiate between the cells of the region and fibers coursing through the region. To test the hypothesis that cells in this region are involved in both the pressor and drinking responses elicited by central administration of angiotensin II, injections of kainic acid were made to induce lesions of the cells, while sparing fibers of passage. Drinking and blood pressure responses were determined pre- and post-lesion in the chronically instrumented awake rat. Injections of 50 ng angiotensin II in a 2-μL volume into a lateral cerebral ventricle of the conscious rat elicited pronounced drinking and pressor responses with a latency of 3–5 min. Lesions of the median preoptic region produced by injecting 1.0 μg of kainic acid in 0.25 μL for 15 s attenuated or blocked the drinking response and increased the latency to drink induced by central injections of angiotensin II. However, kainic acid lesions did not significantly alter the pressor responses produced by angiotensin II administration. These results suggest that cells in the median preoptic region are involved in the drinking response but do not participate in the pressor response elicited by angiotensin II administration into a lateral cerebral ventricle of the conscious rat.
Controls of fetal and neonatal development
Authors: Challis J. R. G.
Published: April 2011

Development during fetal life involves the coordinated maturation of interdependent organ systems—the cardiovascular, central nervous, respiratory, and endocrine axes. Parturition occurs normally when the development of these systems permits extrauterine survival. In most instances, mechanisms exist to ensure synchronous organ maturation and parturition, for example, in the fetal lamb through the widespread mediation of cortisol from the fetal adrenal gland. However, not uncommonly, synchrony is lost. Birth may be precipitated prematurely, through precocious activation of the normal process or through idiopathic mechanisms. In this case, the fetus is born in a state of immaturity. In women, the incidence of preterm labour (delivery before 37 weeks gestation) is 5–9%. Substantial progress has been made in the last 10 years to ensure survival of many of these infants and today even the infant born at a birth weight of 500–750 g, between 24 and 28 weeks of pregnancy, has a 35% chance of survival in the best neonatal intensive care units. However, further progress in improving the survival chances of the prematurely delivered infant, as well as in preventing the preterm delivery of these fetuses, depends on a better understanding of the normal maturational processes of intrauterine life, and of how these are regulated.This symposium touches on four areas of development. These are the pituitary–adrenal axis, the cardiovascular system, the respiratory system, and control of growth. Maturation of the pituitary–adrenal axis is crucial for promoting maturation of many systems and in some species provides the fetal trigger to birth. Substantial adaptation must take place in the cardiovascular system and in the respiratory system as the fetus moves from an environment where oxygen is provided by transplacental transfer from the mother to one of air breathing. Growth is poorly understood at the cellular level, and recent advances using molecular biological techniques have shown that paracrine or autocrine rather than classical endocrine mechanisms may be central to most aspects of fetal growth and development. The intent of this symposium was to highlight recent advances and controversies, and to indicate areas of future challenge. I thank the participants for so ably fulfilling those objectives.
Pentylenetetrazole inhibits glutamate dehydrogenase and aspartate aminotransferase, and stimulates GABA aminotransferase in homogenates from rat cerebral cortex
Authors: Lacoste Lucille , Bartolucci Silvia , Lapointe Jacques
Published: April 2011

The mechanism by which pentylenetetrazole provokes convulsions in animals has been investigated by measuring its influence in vitro on the activities of several enzymes of glutamate metabolism in rat brain homogenates. Pentylenetetrazole does not affect the specific activities of glutamine synthetase, glutaminase, or glutamate decarboxylase; it inhibits those of glutamate dehydrogenase and aspartate aminotransferase, and stimulates that of γ-aminobutyric acid (GABA) aminotransferase. The overall consequence of the action of pentylenetetrazole on the activities of these enzymes should be an increase in the concentration of glutamate and a decrease in that of GABA. This modulation of glutamate and GABA metabolism by pentylenetetrazole could contribute to the triggering of convulsions.
Antiulcerogenic and antisecretory effects of a novel diphenylmethane derivative and antiestrogen binding site ligand
Authors: Glavin Gary B. , Brandes Lorne J.
Published: April 2011

N,N-Diethyl-2-[4-(phenylmethyl)-phenoxy]-ethanamine hydrochloride (DPPE) is a para-diphenylmethane derivative that binds selectively and with high affinity to the microsomal antiestrogen binding site (AEBS). Recent studies with DPPE indicate that AEBS is closely related to a lower affinity non-H1, non-H2 histamine site that may be associated with calcium channels; the DPPE–AEBS site is different from that which verapamil binds, however. DPPE, but not verapamil, demonstrates antiproliferative effects in vitro and is antiestrogenic in vivo. We now show that DPPE profoundly inhibits restraint and cold stress and ethanol-induced gastric ulcer formation, accelerates ulcer healing, attenuates the stress-induced rise in plasma corticosterone level, and significantly reduces basal and H2 agonist (dimaprit)-stimulated and, to a lesser extent, bethanechol-stimulated gastric acid output in conscious rats. A nonulcerogenic but prostaglandin-depleting dose of indomethacin completely blocks the inhibitory effects of DPPE on stress ulcer formation. Conversely, verapamil only slightly attenuates dimaprit-stimulated gastric acid secretion and exacerbates ethanol-induced gastric ulcers; its anti-stress ulcer effects are only partially attenuated by indomethacin. These findings support the likelihood that the site of action of DPPE is different from that of verapamil, and that an effect on prostaglandins may, at least in part, contribute to its antiulcer and apparent cytoprotective effects.
Comparison of cardiovascular response to passive tilt in young and elderly men
Authors: Cunningham D. A. , Petrella R. J. , Paterson D. H. , Nichol P. M.
Published: April 2011

To test the hypothesis that altered hemodynamic responses to postural changes are associated with aging, cardiovascular responses to head-up tilt (HUT) and head-down tilt (HDT) were examined in 12 healthy young (average age, 24.6 ± 1.7 years) and 12 healthy elderly (average age, 68.6 ± 2.2 years) men. Subjects were passively tilted from supine to 30°, 60°, and 90° HUT and HDT. Responses to these perturbations were determined 5 min after tilting with measures of heart rate (HR), blood pressure (SBP, DBP), and echocardiographically determined left ventricular diameter in systole and diastole (LVIDs, LVIDd). In HUT there were no significant age effects. In both young and elderly, SBP decreased significantly (p < 0.05), and DBP and HR increased significantly. Ejection fraction (EF), mean arterial blood pressure (MABP), and rate-pressure product (RPP) were unchanged in both groups. In HDT, the hemodynamic responses of the young and elderly were in opposite directions and significant age effects were found for SBP, DBP, HR, LVIDs, EF, MABP, and RPP. In HDT, the young appear to increase cardiac output primarily due to an increase in EF and end-diastolic volume (LVIDd), while HR is unchanged and SBP is decreased. MABP is unchanged, suggesting a small decrease in total peripheral resistance. The elderly may increase cardiac output slightly, owing to an increase in LVIDd with no change in EF, and a large increase in HR. Afterload increased markedly, therefore attenuating any increase in cardiac output. These results suggest that in healthy men, the cardiovascular response to HUT is not age related, while conversely there appear to be significant differences between young and elderly in response to HDT.
Effect of chronic cysteamine treatment on mouse liver aryl hydrocarbon hydroxylase activity
Authors: Peterson Theresa C.
Published: April 2011

Patients receive chronic cysteamine in the management of nephropathic cystinosis. In a previous report our results indicated that acute cysteamine treatment inhibited cytochrome P-450. Cysteamine (85 mg/kg i.p.) was administered daily to female Swiss mice for 1.5 and 8.5 months. Cysteamine treatment (8.5 months) did not affect hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity compared with controls. A small decrease in liver AHH activity was seen after 1.5 months of treatment with cysteamine. Liver histology, body weight, liver and spleen weights, and serum aminotransferase activity after chronic and subchronic treatment did not differ from controls. Chronic in vivo cysteamine treatment, unlike acute in vitro treatment did not decrease AHH activity. Incubation of isolated murine hepatocytes with cysteamine significantly inhibited AHH activity compared with controls. The inhibition occurred in a concentration-related manner, with 65% inhibition at 8.8 mM (1 mg/mL) (equivalent to the predicted plasma concentration using the maximally tolerable human dose), and 100% inhibition at 44 mM (5 mg/mL). The concentrations used in vitro were not cytotoxic. This suggests that chronic cysteamine treatment may not result in drug interactions and that in vitro results are not always good indicators of in vivo effects.
Cardiovascular responses to V1-vasopressinergic antagonism in conscious versus anesthetized rats
Authors: Brizzee Barbara L. , Walker Benjimen R.
Published: April 2011

Experiments were performed to compare the possible effect of endogenous arginine vasopressin on renal hemodynamics between anesthetized, surgically stressed rats and conscious rats. Animals were instrumented with arterial and venous catheters as well as with a pulsed Doppler flow probe on the left renal artery. The rats were studied under the following conditions: (1) conscious and unrestrained; (2) anesthetized only; (3) anesthetized with minor surgical stress; and (4) anesthetized with major surgical stress. Two anesthetic agents were also compared, a mixture of ketamine (110 mg/kg i.m.) and acepromazine (1 mg/kg i.m.), and sodium pentobarbital (50 mg/kg i.p.). Baseline mean arterial blood pressure was significantly higher in pentobarbital-anesthetized rats following surgical stress compared with conscious animals, but blood pressure was not affected by ketamine–acepromazine anesthesia. After baseline measurements of blood pressure, heart rate, and renal blood flow, a specific V1-vasopressinergic antagonist (d(CH2)5Tyr(Me) arginine vasopressin, 10 mg/kg i.v.) was administered to each group. Mean arterial blood pressure, heart rate, and renal blood flow were monitored for an additional 15 min. Mean arterial blood pressure and renal blood flow decreased after V1 antagonism in ketamine–acepromazine-anesthetized rats with major surgical stress, but were not affected in pentobarbital-anesthetized animals. Heart rate and renal vascular resistance were not affected following V1 blockade with either anesthetic agent. These data suggest that arginine vasopressin plays a role in maintaining blood pressure and renal perfusion in ketamine–acepromazine-anesthetized rats following surgical stress, but does not have a significant effect on renal hemodynamics under pentobarbital anesthesia.
Evidence for regionally selective changes in response to potassium chloride but not vasopressin or methoxamine in vasculature from diabetic rats
Authors: Hebden R. A. , Doroudian A. , McNeill J. H.
Published: April 2011

In the present study we examined the contractile responses of aortae and mesenteric and femoral arteries taken from rats treated 3 weeks previously with streptozotocin (55 mg/kg, i.v.) or saline (1 mL/kg, i.v.) to vasopressin, potassium chloride, and methoxamine. The dose–response curves obtained with vasopressin and methoxamine were not significantly different between control and diabetic animals. However, both the diabetic mesenteric and femoral arteries showed a significantly (p < 0.05) greater maximum response to potassium chloride as compared with their respective controls. The reactivity of the diabetic aortae to this agonist was not different. It is concluded that while the contractile responses of the diabetic tissues were normal when the agonist was vasopressin or methoxamine, there would appear to be regionally selective changes in responsiveness to potassium chloride.
Reduction of ethanol-induced gastric damage by sodium cromoglycate and FPL-52694. Role of leukotrienes, prostaglandins, and mast cells in the protective mechanism
Authors: Beck Paul L. , Morris Gerald P. , Wallace John L.
Published: April 2011

The mechanism of action of the "mast cell stabilizers" sodium cromoglycate and FPL-52694 as protective agents against ethanol-induced gastric mucosal damage was investigated in the rat. Using an ex vivo gastric chamber model, various concentrations (10–80 mg/mL) of the two agents were applied to the gastric mucosa prior to exposure to 40% ethanol. Both agents significantly reduced ethanol-induced damage in a dose-dependent manner. When given orally (80 mg/kg) both agents significantly reduced gastric damage induced by subsequent oral administration of absolute ethanol. Pretreatment with indomethacin did not significantly affect the protection afforded by FPL-52694, but did cause a partial reversal of the protective effect of sodium cromoglycate. Changes in gastric leukotriene C4 synthesis did not correlate with the protective effects of the two agents. Both mucosal and connective tissue mast cell numbers were significantly reduced following oral ethanol administration. In the groups pretreated with FPL-52694 or sodium cromoglycate, mucosal mast cell numbers were not significantly different from those in rats not treated with ethanol. Furthermore, the connective tissue mast cell numbers were significantly lower than in ethanol-treated control rats, despite a >95% reduction of ethanol-induced hemorrhagic damage. These results therefore suggest that stimulation of gastric prostaglandin synthesis is not important in the mechanism of action of FPL-52694, and neither agent appears to reduce damage through a mechanism related to effects on gastric leukotriene C4 synthesis. The present studies further suggest that the protection afforded by pretreatment with sodium cromoglycate or FPL-52694 may be unrelated to effects of these agents on the connective tissue mast cell population in the stomach.Key words: ulcer, eicosanoids, mast cells, alcohol, mast cell stabilizers.
The action and metabolism of peptide leukotrienes in the isolated bullfrog lung
Authors: Heller R. Scott , Herman R. Peter , Herman Ceil A.
Published: April 2011

Leukotrienes (LTs) have been shown to cause contraction of mammalian airway smooth muscle. In this study, LTC4, LTD4, and LTE4 were tested on isolated strips of bullfrog lung. LTC4, LTD4, and LTE4 (10−7 to 3 × 10−10 M) stimulated lung contraction. LTC4 was the most potent, with LTD4 and LTE4 being of equal but lower potency. The cyclooxygenase inhibitors, indomethacin and ibuprofen, had no effect on the strength of leukotriene-induced contraction. In addition, the effects of three mammalian LTD4 receptor antagonists, L-649,923, L-648,051, and LY171883 were tested. All three antagonists failed to block LTC4-simulated contraction, but were effective blockers of LTD4. LTE4-stimulated contractions were significantly blunted by all three antagonists, but the extent of blockade was less than for LTD4. Significant bioconversion of [3H]LTC4 to LTD4 and LTE4 occurred in minced lung preparations but not in lung strips. Peptide leukotrienes caused contraction in amphibian lung, though the order of potency differs from mammals. Like mammals, frogs appear to have two classes of leukotriene receptors, one for LTC4 and one for LTD4–LTE4. These results support the hypothesis that leukotriene receptors have been highly conserved through evolution, despite the fact that the nature of tissue responsiveness to leukotrienes has changed over evolutionary time.Key words: leukotrienes, bullfrogs, receptor antagonists, lung contractility, eicosanoids.
Ionic fluxes induced by topical misoprostol in canine gastric mucosa
Authors: Gana Theophilus J. , MacPherson Brian R. , Ng Dennis , Koo Jarley
Published: April 2011

We studied the dose response of ionic fluxes in canine chambered gastric segment mucosa to increasing doses of topical misoprostol (0.1, 1, 10, 100, and 1000 μg). The fluxes were also correlated with the simultaneous changes in focal gastric mucosal blood flow measured by laser–Doppler flowmetry. After misoprostol administration, there was a dose-dependent increase in focal gastric mucosal blood flow (Emax = 8.23 ± 3.25 V at 10 μg; ED50 = 1.05 μg),pH, and the outputs of ions (Na+, K+, Cl−, and HCO3−) and fluid (Emax for pH and fluxes ≥ 1000 μg). ED50 values for these outputs ranged from 215.40 to 340 μg (mean ± SE = 279.08 ± 24.27 μg). H+ output showed a dose-dependent decrease to zero at the 10-μg dose, the dose at and after which net HCO3− secretion became obvious. The slopes of the dose–response curves for the fluxes of fluid, Na+, K+, Cl−, and HCO3− were significantly different (p < 0.01) from the slope of the curve for mucosal blood flow changes. There were no correlations between the changes in these fluxes and blood flow changes. Na+ and Cl− were the predominant cation (98.84%) and anion (98.19%), respectively, in the misoprostol-induced secretion. Misoprostol stimulates a composite alkaline gastric nonparietal secretion, predominantly Na+ and Cl−, but also containing K+ and HCO3−. Our results suggest different mechanisms for the effects on nonparietal secretion and focal gastric mucosal blood flow. ED50 values for the effects on ionic–fluid fluxes were in the antisecretory dose range,while that for mucosal blood flow changes was in the cytoprotective range.Key words: nonparietal secretion, prostaglandin E1; mucosa, blood flow, stomach.
Differential biotransformation of glyceryl trinitrate by red blood cell – supernatant fraction and pulmonary vein homogenate
Authors: Marks Gerald S. , McLaughlin Brian E. , MacMillan Heather F. , Nakatsu Kanji , Brien James F.
Published: April 2011

We have demonstrated previously that glyceryl trinitrate (GTN) undergoes biotransformation to two glyceryl dinitrate (GDN) metabolites in the human red blood cell – supernatant fraction (RBC–SF) by hemoglobin-mediated and sulfhydryl-dependent enzymatic mechanisms. In the present study, we have shown that biotransformation of GTN in rabbit RBC–SF yields a glyceryl-1,2-dinitrate (1,2-GDN)/glyceryl-1,3-dinitrate (1,3-GDN) ratio of 5.3. Following inhibition of hemoglobin-mediated biotransformation of GTN by carbon monoxide (CO), the 1,2-GDN/1,3-GDN ratio was 2.1. Following inhibition of sulfhydryl-dependent biotransformation by N-ethylmaleimide (NEM), the 1,2-GDN/1,3-GDN ratio was 30.0. We have demonstrated previously that for GTN-induced vasodilation of isolated bovine pulmonary vein (BPV), the 1,2-GDN/1,3-GDN ratio was 7.1, which indicated that a hemoprotein-dependent process was involved in GTN biotransformation. To determine if this was the case, the biotransformation of GTN (0.51 μM) was studied in BPV homogenates; 31.1 pmol GDN/mg BPV protein was formed in 20 min. The 1,2-GDN/1,3-GDN ratio was 1.1, which indicated that hemoprotein-mediated biotransformation did not occur. This conclusion was supported by the fact that CO did not inhibit GTN biotransformation. GTN biotransformation by BPV homogenate was inhibited 62% by NEM, 89% by boiling of the homogenate, and almost completely by boiling plus NEM. These results indicated that biotransformation of GTN by the BPV homogenate involved in a combination of enzymatic and nonenzymatic processes that were mostly sulfhydryl dependent. It is concluded that the mechanism for GTN biotransformation in isolated intact BPV, which yielded preferential formation of 1,2-GDN, was rendered nonfunctional upon tissue homogenization.Key words: glyceryl trinitrate, glyceryl dinitrate, biotransformation, erythrocyte, pulmonary vein.
Blockade of K+ contractures in skeletal muscle by opioid drugs: a nonstereospecific effect
Authors: Kokate Tushar G. , Frank George B.
Published: April 2011

The effect of several opioid drugs was tested on the K+ contractures in frog's skeletal muscle. These contractures are produced by the entrance of extracellular Ca2+ ions via the voltage-dependent, slow Ca2+ channels located in the T tubules. Morphine and other opioid agonists in concentrations ranging from 10−10 to 10−5 M inhibited K+ contractures. The stereoisomers, dextrorphan and levorphanol, were found to have identical potency in inhibiting high K+ contractures, suggesting that this was a nonstereospecific blockade of voltage-dependent calcium channels by the opioid drugs despite the low effective drug concentrations. In agreement with this conclusion it was found that the inhibition of K+ contractures by the opioids was not antagonized by naloxone. It also was observed using a sucrose gap apparatus that these opioid drugs in concentrations used to block the high K+ contractures did not reduce the K+-induced membrane depolarization. Raising the bathing solution Ca2+ concentration from 1.08 to 5 mM produced a reversal of the opioid-induced block of K+ contractures. Finally it was shown that while opioids completely blocked K+ contractures, they did not produce any effect on caffeine contractures showing that opioids do not deplete intracellular Ca2+ stores or inhibit the release of Ca2+ from intracellular sarcoplasmic reticulum stores. It was concluded that several opioid drugs in very low concentrations block K+ contractures in frog's skeletal muscle by a nonstereospecific block of voltage-dependent slow calcium channels.Key words: opioids, calcium channels, contractures, skeletal muscle, opiate receptors, narcotics.
Programmed electrical stimulation-induced arrhythmias in isolated hearts from adult and senescent rats
Authors: Pahor Marco , Gennaro Marco Di , Bernabei Roberto , Gambassi Jr. Giovanni , Carbonin Pierugo
Published: April 2011

In isolated hearts from normal rats, we previously demonstrated an age-related increase of spontaneous ventricular arrhythmias. The aim of the present experiments was to test the possible effect of aging on ventricular arrhythmias induced by programmed electrical stimulation. Experiments were performed in isolated cardiac preparations of 6- and 24-month-old normal Wistar rat hearts. Programmed electrical stimulation (single or double premature stimuli following a stimuli train) was tested in isolated Langendorff perfused hearts during control perfusion, after left anterior descending coronary artery ligature and during global hypoxia. No significant differences were observed between adult and senescent hearts in the incidence of programmed electrical stimulation-induced ventricular arrhythmias during these three different situations. These experiments demonstrate that the cardiac "physiological" aging process is not associated with a greater propensity to programmed electrical stimulation-induced arrhythmias.Key words: Programmed electrical stimulation, aging, rat.
The interaction between carbamazepine and erythromycin
Authors: Turner Patricia V. , Renton Kenneth W.
Published: April 2011

Erythromycin has been reported to interact with the anticonvulsant, carbamazepine, in both children and adults. Toxic serum levels of carbamazepine are observed within 24 h of antibiotic administration, suggesting a mechanism not previously described for other erythromycin-based drug interactions. In rats erythromycin significantly depressed the elimination of carbamazepine in animals induced with carbamazepine for 4 days but had no effect on carbamazepine elimination in noninduced animals. Although the in vitro metabolism of carbamazepine to its epoxide by hepatic microsomes prepared from noninduced rats was significantly inhibited by erythromycin, the inhibition of carbamazepine epoxidation was greatly enhanced in carbamazepine-induced rats. In the pig the sensitivity of carbamazepine metabolism to erythromycin was much greater than in the rat, indicating the existence of a large species difference in this particular drug interaction. It is concluded that the interaction between erythromycin and carbamazepine is caused by a direct inhibition of carbamazepine oxidation by the antibiotic.Key words: carbamazepine, erythromycin, drug interaction, anticonvulsant drugs, antibiotics.
No effect of chronic ethanol administration on the activity of alcohol dehydrogenase and aldehyde dehydrogenases in the near-term pregnant guinea pig
Authors: Card Sharon E. , Brien James F.
Published: April 2011

The objective of this study was to determine the effect of chronic maternal administration of moderate-dose ethanol on alcohol dehydrogenase, low Km aldehyde dehydrogenase, and high Km aldehyde dehydrogenase activities in the guinea pig at near-term pregnancy. The activity of each enzyme in the maternal liver, fetal liver, and placenta of the guinea pig at 59 days of gestation (term, 66 days) was determined spectrophotometrically following chronic daily oral administration of two doses of 1 g ethanol/kg maternal body weight or isocaloric sucrose solution. There was no experimental evidence of ethanol-induced malnutrition in the mother or growth retardation in the fetus. There was a statistically significant increase (65%) in the microsomal cytochrome P-450 content of the maternal liver for the ethanol treatment compared with the sucrose treatment. The alcohol dehydrogenase, low Km aldehyde dehydrogenase, and high Km aldehyde dehydrogenase activities in the maternal liver, fetal liver, and placenta were not statistically different for the ethanol-treated compared with the sucrose-treated animals. This also was the case for the maternal blood and fetal blood ethanol and acetaldehyde concentrations, determined at 2 h after maternal administration of 1 g ethanol/kg maternal body weight. These data demonstrate that the ethanol- and acetaldehyde-oxidizing enzyme activities in the maternal – placental – fetal unit of the guinea pig at near-term pregnancy were not changed by chronic administration of moderate-dose ethanol.Key words: alcohol dehydrogenase, aldehyde dehydrogenases, maternal – placental – fetal unit, ethanol, guinea pig.
Modulatory effects of catecholamines on neurons of the rat visual cortex: single-cell iontophoretic studies
Authors: Kolta Arlette , Reader Tomás A.
Published: April 2011

The catecholamines noradrenaline and dopamine have been proposed as neuromodulators of cortical neuron excitability, and such a regulation could be mediated by specific adrenergic and dopaminergic receptors. We characterized electrophysiologically some of the types of responses to the iontophoretic application of adrenergic and dopaminergic agonists and antagonists on single cells in the rat visual cortex (areas occipital 1 monocular or Oc 1 M and occipital 1 binocular or Oc 1 B). For the majority of spontaneously active and visual cortical cells, noradrenaline and dopamine decreased the firing frequency. In the case of visually driven (synaptically activated) neurons, background firing was the main component of the response to be inhibited by the administration of noradrenaline, clonidine, and oxymetazoline, leading to an enhancement of the signal-to-noise ratio. Since these effects could be reduced or blocked by a previous ejection of the specific α2-antagonist idazoxan, the findings support a role for α2-adrenergic receptors in the transmission of sensory inputs to the visual cortex. These effects were not found with the mixed α-adrenergic agonist phenylephrine nor with the β-agonist isoproterenol. Finally, the use of the inhibitory amino acid GABA rules out a simple hyperpolarizing response as the mechanism underlying noradrenaline modulatory effects in the cerebral cortex.Key words: visual cortex, noradrenaline, dopamine, iontophoresis, neuromodulators.
Mechanism of facilitation of conduction in Purkinje fibers with sequential pacing
Authors: Tchou Patrick , Martin Paul , Wallick Don W. , Crafford William A.
Published: April 2011

Clinical studies have demonstrated that retrograde conduction of a premature beat through the His–Purkinje system can be facilitated by atrioventricular sequential pacing. Several possible mechanisms of facilitation have been proposed. No studies, however, have shown the occurrence of this phenomenon or its mechanism in isolated Purkinje fibers. The present study demonstrated that facilitation of conduction of a premature beat can indeed occur in isolated canine Purkinje fibers during sequential pacing. When a premature beat showed conduction delay during unidirectional pacing, its conduction consistently improved during sequential pacing. This improvement of conduction was related to a greater membrane recovery of a portion of the Purkinje fiber, i.e., the portion that was pre-excited by the sequential mode of stimulation. These findings suggest that an important mechanism of the facilitation of conduction observed clinically may be similar; i.e., pre-excitation and consequent earlier recovery from refractoriness of portions of the His–Purkinje system during atrioventricular sequential pacing.Key words: cardiac electrophysiology, cardiac excitation, supernormal conduction, cardiac refractoriness, atrioventricular sequential pacing.
Angiotensin restores atrial natriuretic factor-induced decrease of baroreceptor sensitivity in normotensive rats, but not in spontaneously hypertensive rats
Authors: Ackermann Uwe , Irizawa Terumi G. , Barber Brett
Published: April 2011

The effect of atrial natriuretic factor (ANF) on baroreflex sensitivity was determined in unanesthetized normotensive (Wistar–Kyoto, WKY) or spontaneously hypertensive rats (SHR) during acute hypertensive stimuli (phenylephrine) or hypotensive stimuli (sodium nitroprusside). The i.v. dose of rat ANF ([Ser99, Tyr126]ANF) was 50 ng/min per rat, sufficient to decrease mean arterial blood pressure (ABP) by about 6 mmHg (1 mmHg = 133.3 Pa) in WKY. SHR showed no change in ABP with this ANF dose. During a control infusion of physiological saline, the mean heart rate (HR) response to increases in ABP was −1.30 ± 0.27 beats/min (bpm)/mmHg in WKY and −0.37 ± 0.22 in SHR (p < 0.05). These values were not affected significantly by ANF. However, ANF blunted chronotropic responses to ABP decreases. The control values of the ΔHR/ΔABP slope in WKY and SHR were −2.34 ± 0.57 and −2.01 ± 0.37 bpm/mmHg, respectively. In the presence of ANF, the slope changed to −0.36 ± 0.43 (i. e., bradycardia in response to hypotension) in WKY and to + 0.20 ± 0.21 in SHR (p < 0.005 for the difference from control for both). This ANF-induced loss of baroreflex sensitivity was reversed in WKY by the addition of angiotensin I (sufficient to increase ABP by 5 mmHg in control rats). Angiotensin did not restore baroreflex sensitivity in ANF-infused SHR, and ANF had no effect on the ABP increase caused by angiotensin in either group. The data suggest that ANF does not act on baroreceptor structures directly, but inhibits mechanisms involved in efferent sympathetic activation. Parasympathetic responses do not appear to be compromised.Key words: atrial natriuretic factor, cardiovascular regulation, baroreceptors.
Exercise inhibits progressive growth of the Morris hepatoma 7777 in male and female rats
Authors: Baracos Vickie E.
Published: April 2011

Male and female rats were either trained to swim for a 6-week period or they remained sedentary. Rats were implanted with Morris hepatoma 7777 after 3 weeks of swimming and were sacrificed after a further 3 weeks. Exercised rats of both sexes showed a significant reduction in tumour weight at sacrifice, compared with sedentary controls (p < 0.01). Similarly, when rats were first implanted with tumours and then placed on an exercise program of 3 weeks duration, tumour growth was also reduced (p < 0.05). These results suggest that the tumour may be sensitive to exercise at more than one point in its development. Tumour growth was inhibited to a similar extent whether the total swimming time was 10, 20, or 30 h over the 3-week period. Although sedentary, tumour-bearing rats were anorexic; both male and female rats showed significant improvement of appetite during the period of tumour growth, in response to exercise. Tumour implantation was associated with significant losses of whole body and muscle protein. The progression of this wasting was not significantly altered by exercise.Key words: Morris hepatoma 7777, cancer, tumour, exercise, skeletal muscle, cachexia, protein.
Postnatal development of adrenergic responsiveness in the rabbit heart
Authors: Feng Z.-P. , Dryden W. F. , Gordon T.
Published: April 2011

It is uncertain how changes in the beta-adrenoceptor population influence the contractility of developing heart. To resolve this we have examined postnatal developmental changes in the adrenergic responsiveness of the rabbit heart. The inotropic effect of isoproterenol on isolated left ventricular papillary muscles from rabbits aged 3, 21, and 90 days was compared with the relative number of beta-adrenoceptors at each age measured using [3H]dihydroalprenolol ([3H]DHA) as the specific ligand. The maximum tension developed in response to isoproterenol increases from 37 ± 7 to 175 ± 33% above control twitch tension between 3 and 21 days of age; this is followed by adecrease to 68 ± 12% in the young adult. During this period of development, there is a decline in EC50 towards increased sensitivity. These differences are partially accounted for by an increase in the numbers of specific [3H]DHA binding sites from 17.3 ± 2.3 to 56.6 ± 9.9 fmol/mg wet tissue weight from 3 to 21 days, and a subsequent decrease to 32 ± 4.5 fmol/mg tissue in the young adult. The proportionally larger increase in contractility compared with the number of beta-adrenoceptor binding sites during the first 3 weeks of life is discussed in terms of the developmental changes in the efficacy of coupling between receptor occupancy and contraction.Key words: beta-adrenergic receptors, cardiac development, neonatal heart, cardiac contractility, neonatal inotropism.
Eicosanoids and heart disease
Authors: Karmazyn Morris , Moffat Margaret P.
Published: April 2011

The discovery of prostaglandins over 5 decades ago heralded a new era in the study of mediators or factors involved in physiological and pathophysiological processes. Prostaglandins, however, do not represent the sole products derived from arachidonic acid or other fatty acid precursors; instead these fatty acids can undergo metabolism to numerous bioactive compounds derived from cyclooxygenase, lipoxygenase, as well as the recently discovered epoxygenase cytochrome P-450 dependent pathways. Collectively, these products are commonly referred to as eicosanoids and have been implicated in numerous biological phenomena. It has long been hypothesized that the prostaglandins play an important role in cardiovascular regulation. For instance, the concept of a balance between the vasoconstrictor, prothrombotic properties of some arachidonic acid derived products and the opposing actions of others led to the development of drug therapies against thromboembolic disorders. Aspirin, for example, a well-known cyclooxygenase inhibitor, has been shown to be efficacious against myocardial infarction and stroke of embolic origin. Moreover, cyclooxygenase- and lipoxygenase-derived products have been implicated in various types of cardiac dysfunction including coronary constriction, arrhythmogenesis, anaphylactic reactions, or ischemic and reperfusion injury.In view of the evolving complexity of arachidonic acid metabolism and increasing evidence that eicosanoids, either alone, or through interaction with other substances, represent important mediators in either the development of heart disease or the myocardial response to injury, we organized this symposium entitled Eicosanoids and Heart Disease concurrent with the 31st Annual Meeting of the Canadian Federation of Biological Societies. A one-half day symposium precludes the possibility of detailed coverage of the many areas in cardiovascular disease in which eicosanoid participation could be implicated and which ideally one would hope to cover. The organizers' aim was to address, in the form of research presentations or reviews, current areas of investigation dealing with selected topics in heart disease.The success of this symposium was made possible by the participation of several distinguished scientists. We would also like to thank the Pharmacological Society of Canada, the Canadian Heart Foundation, Upjohn Canada, Sterling Drug, and Ciba-Geigy U.S. A. for financial support. The organizers thank Dr. J. Burka for serving as Guest Editor and Mrs. L. Hendrickson of this Journal for coordinating the submission of the manuscripts.
Effect of fatty acid composition of dietary fat on energy balance and expenditure in hamsters
Authors: Jones Peter J. H.
Published: April 2011

The comparative effects of feeding diets containing corn, olive, coconut, or menhaden fish oil on efficiency of energy deposition and on short term energy expenditure were examined in growing hamsters. Diets comprising oils mixed with laboratory diets at 10% oil w/w were fed ad libitum for 3 weeks. Animals fed laboratory diets were used as controls. Body composition was determined before and after the feeding period using 3H2O distribution space. Oxygen consumption was measured in each animal during the final week. Weight gains of groups fed corn and olive oil diets exceeded those of the group fed laboratory diet alone (p < 0.05), although metabolizable energy intakes were similar across groups. Corn oil fed animals demonstrated higher carcass energy gains as fat compared with laboratory diet fed or menhaden oil fed groups. This was reflected in an increased fractional deposition of metabolizable energy intake in the group fed corn oil diet compared with the latter two groups. Fecal energy losses were lower in the group fed corn oil diet, and higher in the group fed laboratory diet alone, compared with other groups. Oxygen consumption did not differ between groups. These findings indicate that feeding dietary fish oil, compared with corn oil, favours energy substrate oxidation reducing the fraction of metabolizable energy partitioned for storage.Key words: energy balance, energy expenditure, dietary fatty acids, hamster.
Neomycin prevents indomethacin-induced gastric peristalsis and mucosal injury in the rat
Authors: Mersereau William A. , Hinchey E. John
Published: April 2011

Inhibition of prostaglandin synthesis together with vagally mediated peristaltic contractions are essential if mucosal injury is to occur in the stomach of indomethacin-treated rats. The neomycin group of antibiotics has been shown to interfere with acetylcholine release. Agents blocking peristalsis have been demonstrated to prevent mucosal injury. We postulated that neomycin might inhibit peristalsis and prevent lesion formation. The effect of oral neomycin and bacitracin on gastric wall tone and peristaltic response to indomethacin were assessed and related to the lesion score. Bacitracin had no effect on either response and severe injury occurred. Neomycin did not block the tonal response to indomethacin but abolished peristalsis and no injury occurred. Induction of peristalsis with insulin in neomycin–indomethacin treated rats restored mucosal injury. It is concluded that neuromuscular blockade by neomycin prevented mucosal lesions by preventing peristalsis and not by impairing the ability of indomethacin to inhibit prostaglandin synthesis.Key words: stomach, ulcer, etiology, indomethacin, peristalsis.
β2-Adrenoceptor response in the rat uterus at the end of gestation and after induction of labor with RU 486
Authors: Alj Abdellilah El , Breuiller Michelle , Jolivet André , Ferre Françoise , Germain Guy
Published: April 2011

To study the relationship between the progesterone environment and β-adrenoceptors in the myometrium, rats were treated with the antiprogestin RU 486 (10 mg per rat) at 08:30 h on day 21 of gestation. Under these conditions, more than 60% of animals delivered within 24 h after this treatment, while none of the control animals delivered within the same time period. β-Adrenoceptors were identified using the radiolabeled antagonist (−)-[125I]iodocyanopindolol. The density (Bmax ≈ 33–45 fmol/mg protein) and the affinity (KD ≈ 0.105–0.106 nM) were not changed (during the late stages of gestation) in RU 486 treated rats compared with control rats. These results were correlated with the relaxation of longitudinal and circular strips of myometrium placed in high KC1 medium and exposed to β-adrenoceptor agonists. The adrenoceptors implicated in the relaxation of myometrial strips were mainly of the β2-subtype. There was no difference in their affinity between control and RU 486 treated rats. Mean pA2 values were 8.46 for propranolol and 8.27 for ICI 118-551 against salbutamol. Altogether these results indicate in the rat that the blockade of the action of progesterone at its receptor site by RU 486 did not modify either the affinity or the sensitivity of β2-adrenoceptors in the myometrium, although it induced parturition.Key words: uterus, β2-adrenoceptors, gestation, parturition, RU 486.
Functional studies of nerve projections in the canine intestine
Authors: Daniel E. E. , Kostolanska F.
Published: April 2011

An in vivo model has been developed to study nerve connections in the canine intestine, using spread of field stimulated contractions recorded proximally and distally with strain gauges and local intra-arterial injections of drugs. Excitation spread orally for several centimetres, more effectively at lower frequencies of field stimulation. This excitation was blocked by local hexamethonium or by a combination of atropine and naloxone (each of which reduced the contractions). Distal excitation occurred after a longer delay than oral excitation; during the delay there was frequently an initial relaxation response. Distal excitation was greater at higher frequencies of field stimulation, but like oral excitation it was blocked by hexamethonium or by a combination of atropine and naloxone. Distal relaxation responses were unaffected by atropine or naloxone, but were abolished by hexamethonium. "Off" contractions, those that followed cessation of field stimulation, occurred at higher frequencies of field stimulation proximally and distally near the site of field stimulation and were blocked by atropine but not by naloxone or hexamethonium. The effects of all agents given locally extended beyond the sites of injection. These results suggest that a chain of cholinergic nerves with nicotinic synapses transmit excitation orally and distally to circular muscle; these effects seem to be facilitated proximally and distally by opioid nerves and to be inhibited initially distally by a noncholinergic mechanism. Explanations of these findings are proposed.Key words: opioid nerves, cholinergic nerves, vasoactive intestinal peptide as mediator, naloxone, atropine, hexamethonium, "off"-contractions, field stimulation.
Positive hemodynamic interaction between amrinone and diltiazem in anesthetized dogs
Authors: Dagher E. , Dumont L. , Chartrand C.
Published: April 2011

The direct negative inotropic actions of calcium channel blockers limit the use of these otherwise effective systemic and coronary vasodilators in patients with heart failure. We studied the effects of amrinone pretreatment on the dose – hemodynamic response curve of diltiazem in order to test the hypothesis that amrinone might potentiate diltiazem's positive effects in anesthetized dogs. The control group (no pretreatment, n = 6) had a typical dose-related response to diltiazem (50,100, and 150 μg/kg): coronary and systemic vasodilation, increased stroke volume, and no change in myocardial work and power. Amrinone pretreatment of the study group (n = 7) altered the hemodynamic response, thus maximal systemic vasodilation and stroke volume increase at a lower diltiazem dose, a 15 to 35% increase in myocardial work and power, and more profound coronary vasodilation. We propose that amrinone, by inhibiting phosphodiesterase, potentiates diltiazem vasodilation and reflexly secreted catecholamines' actions on the heart. This positive interaction may permit effective use of lower doses of diltiazem, thus circumventing its dose-limiting direct negative effects while still profitting from beneficial peripheral, reflex, and coronary actions.Key words: diltiazem, amrinone, heart failure, vasodilation, hemodynamics.
Effects of subfornical organ stimulation on respiration in the anesthetized rat
Authors: Ferguson Alastair V. , Beckmann Leslie M. , Fisher John T.
Published: April 2011

The studies reported here have demonstrated that electrical stimulation in the subfornical organ of the urethane-anesthetized rat elicits augmented breaths in over 90% of animals tested. Similar stimulation in immediately adjacent anatomical regions such as the hippocampal commissure was without effect. Detailed analysis of respiratory timing revealed no other significant respiratory effects of such subfornical stimulation.Key words: subfornical organ, respiration.