bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective activation of the adrenal medulla during acute bilateral carotid occlusion and its modulation by α-adrenergic receptors in the rat
Authors: Bouvier Michel , Champlain Jacques de
Published: April 2011

The sympathoadrenal activity was studied during baroreflex stimulation in chloralose anesthetized rats. Circulating norepinephrine (NE) and epinephrine (E) levels were used as indices of sympathetic fiber and adrenal medulla activities, respectively, under basal conditions and during a 1-min bilateral carotid occlusion (CO). In vagotomized rats, the CO induced a significant increase in mean arterial pressure (MAP) associated with an increase in circulating E levels, while this procedure did not alter blood pressure or circulating NE or E levels in intact animals. Following vagotomy, the baroreflex stimulation activated specifically the adrenal medulla, without alteration of the sympathetic fiber activity since the NE levels were not modified by the occlusion. Moreover, in support of that hypothesis, chemical sympathectomy did not decrease the pressure response to CO while bilateral adrenalectomy almost completely abolished this response. The elevation of circulating E induced by the CO was greatly potentiated by pretreatment with Yohimbine, a selective α2-antagonist, and was completely abolished by administration of Clonidine, an α2-agonist, while phenoxybenzamine, which is mainly an α1-antagonist, did not potentiate significantly the E response to CO. These results therefore suggest that the baroreflex activation of the adrenal medulla induced by CO may be modulated in vivo via α2-adrenergic receptors that could be localized on chromaffin cells.
Specificity of hepatic aldehyde dehydrogenase inhibition by calcium carbimide (calcium cyanamide) in the rat
Authors: Loomis C. W. , Brien J. F.
Published: April 2011

Acute, oral administration of 7.0 mg/kg calcium carbimide (calcium cyanamide) to rats, 2 h before sacrifice, produced complete inhibition of hepatic, low-Km (< 1 μM acetaldehyde) mitochondrial and cytosolic aldehyde dehydrogenase enzymes and significantly inhibited high-Km (~ 1 mM acetaldehyde) mitochondrial, cytosolic, and microsomal aldehyde dehydrogenase isozymes. Calcium carbimide had no effect on several other hepatic enzyme activities including mitochondrial glutamate dehydrogenase and monoamine oxidase, cytosolic alcohol dehydrogenase, microsomal NADPH-cytochrome c reductase, benzo[a]pyrene hydroxylase and aminopyrine N-demethylase activities, and microsomal cytochrome P-450 content. It is concluded that calcium carbimide is a more specific inhibitor of hepatic aldehyde dehydrogenase enzymes than disulfiram.
Effect of dietary vitamin A on the mixed function oxidases and the pneumotoxicity of 3-methylindole in goats
Authors: Burley F. E. , Bray T. M.
Published: April 2011

To determine the effects of dietary vitamin A on the activity of the mixed function oxidase (MFO) system and on the susceptibility to 3-methylindole (3MI)-induced respiratory disease, goats were fed a high (supplemented with 12 000 IU retinyl palmitate/kg) or a low (no supplementation) vitamin A diet for 14 weeks. Four animals in each dietary group were then challenged with [14C]3MI. The remaining four animals served as controls. Enzyme assays were performed and severity of the 3MI-induced lung damage was scored. Consumption of the low vitamin A diet resulted in a significant reduction in the liver and lung contents of vitamin A; however, serum concentration of vitamin A was unaffected. High vitamin A supplementation did not alter the activity of the MFO system. Clinical signs, lung – body weight ratio and wet – dry weight ratio of the lungs of 3MI-infused goats were not significantly different; however, in the low vitamin A goats, the microscopic lesions such as the extent of alveolar epithelial hyperplasia were judged to be significantly more severe than those observed in the high vitamin A goats.
Hypertonicity and force development in frog skeletal muscle fibres
Authors: Vaughan Peter C. , Bressler Bernard H. , Dusik Laureen A. , Trotter Martin J.
Published: April 2011

Mechanical experiments were performed on isolated fibre bundles of frog semitendinosus muscle, using solutions made hypertonic by the addition of sucrose or NaCl. Muscle stiffness was measured with 1-ms step changes of length, from the plateau of an isometric tetanus. Within 20 min in hypertonic Ringer, isometric tetanus tension fell by 50% or more. The rate of tension redevelopment following stepwise shortening was reduced in hypertonic solution. Point voltage clamp studies showed that even when isometric tension had fallen to this extent, the stimulus strength–duration relation for mechanical activation was identical to that for controls. Point voltage clamp was used to intermittently repolarize fibres depolarized in solutions of high ionic strength, reactivating the excitation contraction coupling mechanism. Subsequent depolarization of the fibres allowed a visual test to be made of the fibres' ability to contract. The period during which contraction could be seen grew shorter as the ionic strength of the bathing medium was raised. The results of these different types of mechanical experiments suggested that the increased intracellular ionic strength caused by osmotic shrinkage in hypertonic Ringer's solution slows the rate at which individual cross bridges can form and develop tension, as well as reducing the maximum amount of tension they can generate. Muscle stiffness did not remain at control level in hypertonic solution; nor did it fall as much as did developed tension. The most obvious, although not the only, interpretation of this observation was that cross bridges are less stretched when isometric force is reduced and the length–tension relation of the elastic element is nonlinear.
Changes of catecholamines in central and peripheral tissues and in the urines of deoxycorticosterone–salt hypertensive rats
Authors: Buu Nguyen T. , Kuchel Otto , Genest Jacques
Published: April 2011

The catecholamine concentrations in the urines and in the tissues of the kidney, heart, striatum, and hypothalamus of control rats and rats treated with deoxycorticosterone and salt for 2-week and 5-week periods were measured and compared. In 2-week-treated rats there were no changes in blood pressure and catecholamines. In 5-week-treated rats, the blood pressure increased from 117 ± 5 to 152 ± 5 mmHg (1 mmHg = 0.13 kPa) and there was an increase of urinary dopamine, norepinephrine, and epinephrine. The kidney and heart tissues of the hypertensive rats showed a decrease of norepinephrine while in the hypothalamus all three catecholamines were increased. These data suggest that dopamine and epinephrine may also be involved in the sympathetic dysfunction in deoxycorticosterone–salt hypertension. They demonstrate for the first time an increase of dopamine, norepinephrine, and epinephrine in the hypothalamus of deoxycorticosterone–salt hypertensive rats.
Nalorphine: actions at an opiate receptor on frog skeletal muscle fibers
Authors: Ary Thomas E. , Frank George B.
Published: April 2011

Intracellular microelectrode studies were conducted to investigate the actions of the partial agonist – antagonist nalorphine at an opiate receptor on functional frog skeletal muscle fiber membranes. In high bath concentrations (≥ 10−4 M), nalorphine alone produces agonist actions similar to the "full" opiate agonists. These actions were (i) to depress both the sodium and potassium (gNa and gK) conductance increases due to electrical stimulation by a nonspecific local anestheticlike mechanism and (ii) to depress gNa by a specific opiate receptor mediated mechanism. In a much lower bath concentration (1 × 10−8 M) nalorphine acts to antagonize the specific opiate receptor mediated depression of gNa produced by the "full" agonist meperidine. Thus in this preparation nalorphine, "the partial antagonist," has the same actions as naloxone, which is often considered to be a full antagonist. The quantitative differences observed in the effects of these two opiate antagonists are discussed.
Heart rate as a determinant of the decay rate of the cardiac inotropic response to sympathetic nervous activity
Authors: Masuda Yukitaka , Levy Matthew N.
Published: April 2011

The cardiac responses to sympathetic nerve stimulation were measured in a series of open-chest, anesthetized dogs. In half the animals, the hearts were in a sinus rhythm; in the remaining animals, the hearts were in an atrioventricular (AV) junctional rhythm. Cocaine markedly prolonged the decay times of the chronotropic responses after cessation of sympathetic stimulation, regardless of the type of rhythm. The decay times of the inotropic responses were only slightly prolonged by cocaine in animals with a sinus rhythm, but the prolongations were pronounced in animals with an AV junctional rhythm. The lower basal heart rate appeared to be more responsible for the greater decay times of the inotropic responses in the animals with an AV junctional rhythm than in those with a sinus rhythm. In a second series of dogs, complete heart block was produced, cocaine was given, AND the hearts were paced at four different frequencies. The mean decay time of the inotropic response to sympathetic stimulation varied inversely AND substantially with the pacing frequency. The change in contraction frequency probably affects the rate of neurotransmitter dissipation from the ventricular myocardium, by altering either the coronary blood flow or the massaging action of the cardiac contractions.
High-dose ascorbic acid decreases detoxification of cyanide derived from amygdalin (laetrile): studies in guinea pigs
Authors: Basu Tapan K.
Published: April 2011

Cysteine, a sulphur-containing amino acid, is required to metabolize ascorbic acid (as ascorbate sulphate) and detoxify cyanide (to thiocyanate). In guinea pigs, conjoint use of laetrile (a cyanogenic glycoside) and ascorbic acid (in large doses) decreases the detoxification of cyanide derived from laetrile through diminishing the availability of cysteine, but not impairing hepatic rhodanese activity, which is involved in the detoxification of cyanide to thiocyanate. These results agree with the symptoms of a sublethal dose of KCN toxicity manifested by the animals. The studies, therefore, indicate that individuals taking megadoses of ascorbic acid concurrently with laetrile may be subject to self-poisoning.
Renal enzymes during experimental diabetes mellitus in the rat. Role of insulin, carbohydrate metabolism, and ketoacidosis
Authors: Lemieux Guy , Aranda Manuel Rengel , Fournel Pierrette , Lemieux Christiane
Published: April 2011

The activities of various ammoniagcnic, gluconeogenic, and glycolytic enzymes were measured in the renal cortex and also in the liver of rats made diabetic with streptozotocin. Five groups of animals were studied: normal, normoglycemic diabetic (insulin therapy), hyperglycemic, ketoacidotic, and ammonium chloride treated rats. Glutaminase I, glutamate dehydrogenase, glutamine synthetase, phosphoenolpyruvate carboxykinase (PEPCK), hexokinase, phosphofructokinase, fructose-1,6-diphos-phatase, malate dehydrogenase, malic enzyme, and lactate dehydrogenase were measured. Renal glutaminase I activity rose during ketoacidosis and ammonium chloride acidosis. Glutamate dehydrogenase in the kidney rose only in ammonium chloride treated animals. Glutamine synthetase showed no particular variation. PEPCK rose in diabetic hyperglycemic animals and more so during ketoacidosis and ammonium chloride acidosis. It also rose in the liver of the diabetic animals. Hexokinase activity in the kidney rose in diabetic insulin-treated normoglycemic rats and also during ketoacidosis. The same pattern was observed in the liver of these diabetic rats. Renal and hepatic phosphofructokinase activities were elevated in all groups of experimental animals. Fructose-1,6-diphosphatase and malate dehydrogenase did not vary significantly in the kidney and the liver. Malic enzyme was lower in the kidney and liver of the hyperglycemic diabetic animals and also in the liver of the ketoacidotic rats. Lactate dehydrogenase fell slightly in the liver of diabetic hyperglycemic and NH4Cl acidotic animals. The present study indicates that glutaminase I is associated with the first step of increased renal ammoniagenesis during ketoacidosis. PEPCK activity is influenced both by hyperglycemia and ketoacidosis, acidosis playing an additional role. Insulin appears to prevent renal gluconeogenesis and to favour glycolysis. The latter would seem to remain operative in hyperglycemic and ketoacidotic diabetic animals.
Ca2+ handling properties of microsomal subfractions of rat vas deferens smooth muscle
Authors: Grover A. K. , Kwan C. Y.
Published: April 2011

The rat vas deferens smooth muscle microsomes on isopycnic centrifugation gave two fractions, namely F2 (15–30% sucrose) and F3 (30–40% sucrose), with comparable ATP-dependent azide-insensitive Ca2+-uptake capacities, although these fractions differed from each other in various enzyme marker activities. The fractions F2 and F3 also show similar pH profiles for the ATP-independent and ATP-dependent Ca2+ uptake, and similar ionized Ca2+-concentration dependence for the ATP-dependent Ca2+ uptake. However, the fractions F2 and F3 differ from each other in that: (a) F3 shows higher permeability to Ca2+, and (b) F3 shows higher stimulation of the ATP-dependent Ca2+ uptake by oxalate. The F3 fraction can also be used to obtain membrane vesicles loaded with Ca2+ oxalate in the presence of ATP. However, the yield of the Ca2+ oxalate enriched fraction is too low to permit their further characterization.
Effect of noradrenaline on oxygen consumption and tissue blood flow in young pigs
Authors: Jamieson Linda , Stribling D. , Rothwell Nancy J. , Stock M. J.
Published: April 2011

Metabolic rate and tissue blood flow were measured by indirect calorimetry and the radioactive microsphere technique, respectively, in anaesthetized pigs aged 10, 17, and 28 days during infusions of saline or noradrenaline. Noradrenaline produced a rise in oxygen consumption in all pigs but the magnitude of the response declined with age in Large White pigs (percent increase: 10 days old, 29.5 ± 3.3; 17 days old, 15.3 ± 3.2; 28 days old, 5.4 ± 0.17) and was less in 10-day-old Minipigs (9.1 ± 5.1). Regional blood flow per gram of tissue was similar for pigs of all ages and noradrenaline produced increases in flow to heart and skin, and small reductions in blood flow to skeletal muscle. Noradrenaline increased average blood flow to adipose tissue (four sites) by 21-fold in 10-day-old Large White pigs, but had less effect in 10-day-old Minipigs (9.5-fold) and in older Large White pigs (9-fold), where the effect on metabolic rate was diminished. It is calculated that adipose tissue could be responsible for the increase in metabolic rate during infusion of noradrenaline. Macroscopically there are no gross differences between various adipose tissue depots in the pig but those which showed the greatest response to noradrenaline correspond to areas where brown adipocytes have previously been identified by electron microscopy.
Calcium reactivity and antagonism in portal veins from spontaneously hypertensive and normotensive rats
Authors: Harris A. L. , Swamy V. C. , Triggle D. J.
Published: April 2011

Reactivities of portal veins from spontaneously hypertensive rats (SHR) and normotensive controls (Wistar Kyoto, WKY) at 5–7 and 15–17 weeks of age were compared. Systolic blood pressures were not different at 5–7 weeks but those of SHR were significantly elevated (177 ± 4 mmHg) (1 mmHg = 133.322 Pa) at 15–17 weeks. Spontaneous activity, frequency, and tension were greater in SHR for both age groups. Young SHR were more sensitive to K+ at 5–7 weeks but less sensitive at 15–17 weeks than age-matched WKY rats. Sensitivity to Ca2+ in a K+-depolarizing medium was higher in SHR than in WKY for both age groups. Maximum tension responses to K+ or Ca2+ were greater in SHR. The Ca2+ channel antagonists nifedipine, nitrendipine, and nisoldipine were potent inhibitors of both noradrenaline- and K+-induced responses but did not show differences in inhibitory activity between WKY and SHR.
Tetrodotoxin-resistant release of ATP from superfused rabbit detrusor muscle during electrical field stimulation in the presence of luciferin–luciferase
Authors: Chaudhry Archana , Downie John W. , White Thomas D.
Published: April 2011

The present study was carried out to assess the possible role of ATP in the noncholinergic, nonadrenergic transmission in the rabbit urinary bladder. When rabbit detrusor muscle strips were superfused with medium containing firefly luciferin–luciferase and stimulated transmurally at low stimulation parameters, tetrodotoxin-sensitive contractions were obtained but no release of ATP could be detected. However, at somewhat higher stimulation parameters, release of ATP was observed. This release of ATP was not diminished by tetrodotoxin indicating that ATP was not likely released as a result of propagated action potentials in nerves. Because contractions persisted in the presence of tetrodotoxin, it is possible that the ATP might have been released as a result of direct electrical stimulation of the muscle. These results do not support the idea that ATP is released as a neurotransmitter in the rabbit bladder.
Effects of dihydroergotamine on hemodynamic molsidomine actions in anesthetized dogs
Authors: Fiedler Volker B. , Göbel Helmut , Nitz Rolf-Eberhard
Published: April 2011

In pentobarbital-anesthetized mongrel dogs the intravenous actions of 0.50 mg/kg molsidomine on pulmonary artery and left ventricular (LV) end-diastolic pressures and internal heart dimensions (preload), left ventricular systolic and peripheral blood pressures, and total peripheral resistance (afterload), as well as on heart rate, dP/dt, stroke volume, and cardiac output (heart performance) were studied for 2 h. Hemodynamic molsidomine effects were influenced by increasing amounts of intravenously infused dihydroergotamine solution (DHE, 1–64 μg∙kg−1∙min−1). Molsidomine decreased preload, stroke volume, and cardiac output for over 2 h but decreased ventricular and peripheral pressures for 45 min. Systemic vascular resistance showed a tendency to decrease while heart rate and LV dP/dtmax were not altered. DHE infusion reversed molsidomine effects on the preload and afterload of the heart. The diminished stroke volume was elevated so that cardiac output also increased. Total peripheral resistance increased while heart rate fell in a dose-dependent fashion. The LV dP/dtmax remained unchanged until the highest dose of 64 μg∙kg−1∙min−1 DHE elevated the isovolumic myocardial contractility. These experiments indicate that DHE can reverse the intravenous molsidomine effects on hemodynamics. Most likely, this is mediated through peripheral vasoconstriction of venous capacitance vessels, thereby affecting moldisomine's action on postcapillary beds of the circulation.
Depletion of cardiac noradrenaline stores by the calcium-channel blocker D-600
Authors: Chaudhry A. , Vohra M. M.
Published: April 2011

The actions of the calcium-channel blocker D-600 on cardiac noradrenaline stores were investigated by giving rats the drug systemically and then using a high-performance liquid chromatograph equipped with an electrochemical detector to determine the noradrenaline content of their hearts. A single 5-mg/kg dose of D-600 caused a significant depletion of noradrenaline content of the ventricles (approximately 31%) but not of the auricles. However, when multiple doses of D-600 were given at 12-h intervals, the depletion of cardiac noradrenaline content was more marked and both the auricular and ventricular contents were significantly decreased. Depletion of noradrenaline content was maximal 4 h after administration of D-600. A partial recovery of noradrenaline content occurred 16 h after administration of D-600, indicating that this effect of D-600 is reversible. In in vitro studies, D-600 (10−7 to 10−3 M) evoked a dose-related increase in the basal outflow of tritium from the rat isolated atria preloaded with [3H]noradrenaline ([3H]NA), indicating that depletion of cardiac noradrenaline stores by D-600 may be due to a direct action on sympathetic nerves rather than to increased reflex sympathetic activity secondary to profound vasodilation caused by the drug. The metabolic profile of tissue 3H content and of D-600-evoked 3H overflow was also examined. Whereas >90% of tissue 3H content consisted of unchanged [3H]NA, 60–70% of the D-600-evoked overflow consisted of [3,4-3H]dihydroxyphenylglycol, and approximately 5% was unchanged NA, thus indicating that D-600 causes release of [3H]NA intraneuronally. It is concluded that this property of D-600 might be responsible for the depletion of endogenous cardiac noradrenaline stores after systemic administration of the drug to rats.
Possible role of histamine in brain function: neurochemical, physiological, and pharmacological indications
Authors: Mazurkiewicz-Kwilecki I. M.
Published: April 2011

Recently accumulated neurochemical, physiological, and pharmacological evidence strongly supports a role for histamine as a central neurotransmitter. Neurochemical methods, which became available within the last years, allow determination of small amounts of histamine and its metabolites in the brain and make possible future studies of central histamine regulation. The demonstration of histamine H1 and H2 receptors in the brain of several species suggests a possible role for histamine in brain function. Microelectrophysiological studies on single central neurones suggest both excitatory and depressant effects of histamine which are receptor mediated. In addition, brain histamine has been demonstrated to be subject to cyclic variations, to play a role in hormonal regulation, and to be altered by stressful conditions. Several psychotropic drugs significantly affect brain histamine regulation and elicit inhibitory effects on central histamine receptors. These findings bring new approaches and stimulus to further research on the significance of brain histamine.
Histamine and the heart
Authors: McNeill John H.
Published: April 2011

Histamine has been known as a cardiac stimulant for over 70 years. Work in our laboratory over the past decade has established that histamine receptors exist in the hearts of various species. The type of histamine receptor varies not only between species but also in the various regions of the heart. In the guinea pig heart H1 receptors are found in left atria and ventricles while H2 receptors are found in right atria and are the predominant histamine receptor in the ventricles. Rabbit atria contain both H1 and H2 receptors while the ventricles appear to possess only H1. Rat and cat heart do not seem to have histamine receptors and the positive inotropic and chronotropic effects elicited by histamine in cardiac preparations of these species are due to the release of noradrenaline. Dog heart contains H1 receptors while human heart has H2 receptors. In all cases H2 receptors are associated with adenylate cyclase and stimulation of such receptors results in an increase in cyclic AMP levels. H1 receptors are not associated with cyclic nucleotides in the heart. There are certain similarities between β-adrenergic and H2-histaminergic receptors as well as between α-adrenergic and H1-histaminergic receptors. Stimulation of either histamine receptor must result in an increase in the free calcium ion concentration in the cardiac cell but the mechanisms involved are obviously different.
The 12th J. A. F. Stevenson Memorial Lecture: Aging, Alzheimer's disease, and the cholinergic system
Authors: McGeer Patrick L.
Published: April 2011

Aging does not affect tissues in a uniform fashion. Within the brain, substantial neuronal dropout occurs with age in the cholinergic medial basal forebrain complex, the noradrenergic locus coeruleus, and the dopaminergic substantia nigra pars compacta. These areas are also struck by diseases that are sharply age dependent. Alzheimer's disease causes neuronal destruction in the cholinergic cells of the medial basal forebrain and noradrenergic cells of the locus coeruleus. Parkinson's disease causes neuronal destruction mainly in the substantia nigra but with some destruction in the locus coeruleus. Parkinsonism–dementia affects all three areas. Alzheimer's disease is responsible for 50–60% of all cases of dementia. Severe dementia rises in frequency from less than 1% of the population at age 65–70 to over 15% by age 85. The cause of the disease is unknown. No method of prevention is known and present treatments are ineffective, although modest improvement has been reported for various therapeutic regimens designed to stimulate the cholinergic system. The neuronal systems identified as being affected in Alzheimer's disease and in the dementia of Parkinsonism correspond with those shown many years ago to be associated with the reticular activating system. This correspondence permits a new hypothesis of cognition and memory to be put forward, as well as a reinterpretation of data from animal research on the reticular activating system performed over a quarter of a century ago. The locus coeruleus is proposed as the noradrenergic element sensitizing the cortex to conscious recognition of real time events. The medial basal forebrain complex is proposed as the system registering the conscious event for storage and as the readout device when it is subsequently redisplayed in the cortex as memory. Storage could either be in the temporal lobe, in several areas of cortex with feedback to the medial basal forebrain, or in the cholinergic cells themselves.
Control of right atrial pressure at constant cardiac output suppresses volume natriuresis in anesthetized rats
Authors: Ackermann U. , Rudolph J. R.
Published: April 2011

The blood volume of anesthetized rats was expanded acutely by 33% with donor blood while a caval snare was gradually tightened so that right atrial pressure (RAP) was prevented from rising (n = 6). In control experiments (n = 5) an aortic snare was used to hold mean arterial blood pressure near the values found in the experimental series. However, RAP was allowed to change freely and increased by 1.6 ± 0.4 mmHg (1 mmHg = 133.322 Pa) during volume expansion. When the two groups were compared, there were no significant differences between their mean arterial blood pressures (near 110 mmHg) or in their cardiac outputs (near 0.25 mL∙min−1∙g body weight−1). There were, however, significant differences between their renal responses to the volume load. When RAP was free to change, the rate of volume excretion [Formula: see text] increased to 30 ± 15 (SEM) μL∙min−1∙g kidney weight−1 (KW) from its control value of 3.49 ± 0.31 and the rate of sodium excretion [Formula: see text] increased to 3.59 ± 0.20 μequiv.∙min−1∙g KW−1 from its preinfusion value of 0.42 ± 0.10. When RAP was not allowed to increase during volume loading, [Formula: see text] and [Formula: see text] did not change from their respective preinfusion values (2.99 ± 0.46 μL∙min−1∙g KW−1 and 0.35 ± 0.10 μequiv.∙min−1∙g KW−1). The results imply that during acute blood volume expansion increased central vascular pressure is a prerequisite for the homeostasis of body water and salt.
The effects of hyperoxia on oxygen uptake during acute anemia
Authors: Chapler C. K. , Cain S. M. , Stainsby W. N.
Published: April 2011

The effects of normobaric hyperoxia on the oxygen uptake [Formula: see text] and cardiovascular responses of the whole body and hindlimb during anemia were investigated. Anesthetized, paralyzed dogs were ventilated for 20-min periods with room air (normoxia), 100% O2 (hyperoxia), and returned to room air. Anemia (hematocrit = 15%) was then induced by isovolemic dextran-for-blood exchange and the normoxia, hyperoxia, normoxia sequence was repeated. Whole body [Formula: see text] and cardiac output rose following anemia, and then fell (p < 0.05) with hyperoxia during anemia. These responses were not abolished by β-blockade with propranolol (1 mg/kg, iv) or bilateral vagotomy. The hindlimb data for blood flow and [Formula: see text] were similar in direction to those of the whole body but were more variable. Section of the sciatic and femoral nerves did not appear to have significant effect on the limb responses to hyperoxia. The decrease in whole body and hindlimb [Formula: see text] with hyperoxia during anemia may have resulted from a redistribution of capillary blood flow away from exchange vessels in response to the elevated [Formula: see text].
Seasonal changes in the secretion of gonadotropic hormones and in the endocrine response of the pituitary of male sheep in the absence of gonadal influence
Authors: Sanford L. M. , Howland B. E. , Palmer W. M.
Published: April 2011

Circulating levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL) were assessed in four long-term castrate rams at monthly intervals for 1 year beginning in March. Each month, rams were bled from the jugular vein at 10-min intervals for an 8-h period; 10 μg synthetic gonadotropin releasing hormone (GnRH) was injected into the jugular vein following 6 h of sampling. Changes in natural daylength were associated with seasonal variations in mean serum levels of LH (r = 0.57, P < 0.05) and PRL (r = 0.94, P < 0.01). LH levels declined 55% between June and October as LH peaks became more frequent and progressively smaller in magnitude, and base-line levels decreased; these trends were reversed by December. In comparison, FSH levels increased 40% between June and September and then returned to relatively low values in October. Seasonal variations in the magnitude of endogenous LH pulses were not associated with definitive changes in the LH response of the pituitary to exogenous GnRH. Although LH and FSH levels in the castrate rams were typically high, many of the seasonal-directional changes in the secretory characteristics of these hormones (i.e., LH peak frequency and magnitude, and mean FSH level) were similar to those reported for the intact ram. Data indicate that photoperiodic regulation of hypothalamic function of rams is in part via direct or steroid-independent means.
Systolic blood pressure responses to enalapril maleate (MK 421, an angiotensin converting enzyme inhibitor) and hydrochlorothiazide in conscious Dahl salt-sensitive and salt-resistant rats
Authors: Sharma J. N. , Fernandez P. G. , Kim B. K. , Triggle C. R.
Published: April 2011

Systolic blood pressure responses to enalapril maleate (MK 421, a new angiotensin converting enzyme inhibitor (CEI)) and hydrochlorothiazide (HTZ) were studied in conscious Dahl salt-sensitive (DS) and salt-resistant (DR) rats maintained on a high salt (8.0% NaCl) and a normal salt (0.4% NaCl) diet. The DS rats were severely hypertensive after 3 weeks on the high salt diet whereas the systolic blood pressure (SBP) of the DR rats were normotensive. Oral treatment with enalapril (15–100 mg∙kg−1∙day−1) and HTZ (60–400 mg∙kg−1∙day−1) caused a significant reduction of SBP in the DS rats with the high salt diet (P < 0.001); however, this was not observed until after 4 weeks of treatment when the dosage was 30 and 150 mg∙kg−1∙day−1, respectively. Furthermore, enalapril therapy alone significantly reduced the SBP of all groups of rats regardless of diet or Dahl strain (P < 0.001), but this was not observed until the end of the 7th week of therapy in DR rats on 8.0% NaCl and the end of the 3rd week of therapy for DR and DS rats on 0.4%) NaCl. These results suggest that enalapril may lower SBP by mechanisms other than those related to an action as a CEI.
Evaluation of topical phenol as a means of producing autonomic denervation of the liver
Authors: Lautt W. Wayne , Carroll Anne M.
Published: April 2011

Topical application of 90% phenol around the bile duct, portal vein, and hepatic artery, as well as along each of the three hepatic ligaments was tested for effectiveness of rapid and chronic denervation in cats. Because phenol produces nonselective nerve degeneration, it was assumed that proof of functional sympathectomy was adequate proof of disruption of parasympathetic and afferent nerves as well. Functional sympathetic neurons were evaluated by measuring physiological responses to direct electrical stimulation of the anterior hepatic plexus. Acute or rapid denervation was assessed by the degree of rise in portal blood pressure produced by nerve stimulation. Complete denervation appeared within 20 min and was still present by 80 min postapplication. Chronic denervation was tested by applying the phenol and recovering the cats for 6–14 days. An equal number (n = 6) of sham-denervated cats were compared. Phenol denervation did not alter basal glucose, insulin or glucagon levels, hematocrit, blood pressure, or hepatic glycogen levels. These variables are a good index of stress and metabolic status. Nerve stimulation in the chronic sham group raised portal pressure, arterial pressure, and blood glucose levels, whereas the chronic-denervated group showed no responses. The health of the two groups appeared normal with the sole difference being that the painted itssues were mildly discolored and more adhesions appeared in the phenol-denervated set. Thus phenol is a useful tool for producing hepatic denervation. It is less traumatic, faster, and more certain than surgical denervation. In addition, the hepatic lymphatics can be preserved using the topical application of phenol.
A human cytochrome P-450 characterized by inhibition studies as the sparteine–debrisoquine monooxygenase
Authors: Inaba T. , Nakano M. , Otton S. V. , Mahon W. A. , Kalow W.
Published: April 2011

The present study compares the debrisoquine monooxygenase and the sparteine monooxygenase activities of human liver microsomes. In the presence of 14 competitive inhibitors, apparent inhibition constants (Ki) as determined by these two activities ranged over four orders of magnitude with a correlation coefficient 0.99. These in vitro results represent the strongest evidence to date that the debrisoquine monooxygenase and the sparteine monooxygenase are identical and involve a single isozyme of cytochrome P-450.
Transmembrane calcium transport and the activation of cardiac contraction
Authors: Horackova Magda
Published: April 2011

It has been known for a century that extracellular Ca2+ ions are needed for triggering contraction in the heart. However, the two possible mechanisms of Ca2+ entry into the cardiac cells have only been discovered and investigated recently: these are the voltage-gated Ca2+ channels and the Na+–Ca2+ exchange. This paper reviews the field of the control of cardiac contractility by the sarcolemma and describes various techniques used to study the Ca2+ transport and the corresponding two components of contraction: phasic and tonic tension. The most controversial issue of the past 5 years, attracting the attention of many investigators, is whether or not the Na+–Ca2+ exchange in the heart is electrogenic and voltage-dependent and thus contributes to the beat-to-beat regulation of free intracellular [Ca2+]. This paper concentrates on this controversy and gives an up-to-date view of the major steps in the development of our present concept of this transport and of some of the recent experimental approaches. The contribution of an electrogenic, voltage-dependent Na+–Ca2+ exchange to the regulation of contraction, as well as to cardiac electrical activity, is discussed, and the alterations of both of these cardiac functions due to Na+ accumulation intracellularly (owing to various interventions) are described.
Temporal correlation of changes in rat brain sialic acid and in inhibition of Na+–K+ ATPase with ethanol tolerance
Authors: Rangaraj N. , Beaugé F. , Kalant H.
Published: April 2011

Administration of ethanol to rats by gavage, in daily doses increasing gradually from 3 to 6 g/kg, led to progressive development of tolerance to the hypothermic effect of test doses of ethanol (3 g/kg, i.p.), between days 4 and 21 of treatment. Tolerance was decreased by day 3 of withdrawal, and had disappeared by day 7. Basal levels of brain microsomal Na+–K+ ATPase activity increased progressively during tolerance development, and returned to normal by 4 days after ethanol withdrawal. Conversely, inhibition of the ATPase by ethanol alone (0.22–0.66 M), or by 1 μM norepinephrine (NE) combined with much lower concentrations of ethanol (0.0125–0.1 M), decreased progressively during tolerance development, and returned to normal after withdrawal. The best temporal correlation with the degree of tolerance was shown by the magnitude of NE sensitization of the enzyme to ethanol inhibition. The chronic sucrose control treatment resulted in an unexplained increase in the NE sensitization. Since synaptosomal membrane concentration of sialic acid showed a similar time course during ethanol treatment, it is possible that changes in membrane sialic acid contribute to the alteration in NE sensitization by altering NE receptor properties.
Succinic dehydrogenase activity of forelimb and hindlimb muscles of the dystrophic mouse
Authors: Parry D. J. , Desypris G.
Published: April 2011

The activity of succinic dehydrogenase (SDH) was determined in muscles of normal and dystrophic mice. In contradistinction to reports based solely upon histochemical examination, we were unable to observe increased activity in fast-twitch muscles of dystrophic mice. Because dystrophic muscles contain large amounts of connective tissue, two reference bases for expression of enzyme activity were compared. SDH activity was expressed either per micromole of creatine or per milligram of "true muscle fibre weight." The latter was obtained by determining the proportion of the whole muscle occupied by muscle fibres using an image analyzer with photographs of muscle cross section. It appears that the use of creatine content as an index of muscle mass may not be valid for pathological tissue, as the concentration of creatine in some dystrophic muscles differed from that of control muscles. Hindlimb muscles of dystrophic mice exhibit continuous spontaneous activity. To determine the effects of this on oxidative enzyme activity two fast-twitch muscles from the forelimb were also examined. Although they showed histochemical changes comparable to those seen in hindlimb muscles, there was no increase in SDH activity. The only dystrophic muscle examined which showed a change in SDH activity was the soleus in which a decrease was observed.
Effects of renal denervation on the renal responses of anesthetized rats to cyclohexyladenosine
Authors: Cook Curtiss B. , Churchill Paul C.
Published: April 2011

In the present experiments, we tested the hypothesis that renal denervation would attenuate or abolish some of the renal effects of cyclohexyladenosine, a nonmetabolized adenosine receptor agonist. A paired design (left kidney sham-denervated or denervated versus the innervated right kidney) was used in anesthetized rats. Intravenous cyclohexyladenosine (2.3 nmol/min) reduced para-aminohippurate and inulin clearances in both denervated and sham-denervated kidneys; these effects were increased rather than decreased in denervated kidneys. Similarly, cyclohexyladenosine decreased the excretion of Na+ and K+ more in denervated than in innervated kidneys. Renal plasma flow was decreased by cyclohexyladenosine, without a corresponding increase in the arteriorenal venous difference in plasma renin concentations, and arterial plasma renin concentration decreased in all rats given cyclohexyladenosine, suggesting inhibition of renin secretion. No differences in the latter variables were noted in denervated versus sham-denervated kidneys. Since cyclohexyladenosine produced effects in denervated kidneys which were equal to or greater than the effects in sham-denervated kidneys, it is concluded that these effects are mediated by direct actions, rather than by inhibition of transmitter release from the renal nerves.
Acid rain and soil
Authors: VanLoon G. W.
Published: April 2011

A summary of important chemical properties of soil is given and the way in which acid rain may affect these properties is discussed. Acid rain may suppress microbiological decomposition and nitrification processes, thus influencing the nutrient status of soils. It has also been found that soil organic matter is less soluble in more acid solutions. Changed nutrient availability patterns are predicted in a low pH environment and enhanced leaching of essential elements from the soil exchange complex has been observed. Increased solubility of potentially toxic elements such as aluminium may also occur from soils which have been exposed to acidified rainfall.
Neurotoxicity of aluminum
Authors: Boegman R. J. , Bates L. A.
Published: April 2011

Aluminum is the most abundant metal and the third most common element. Soluble aluminum salts can be absorbed from the stomach and the metal is deposited in the gray matter in the brain. Following exposure to aluminum, aggregates of neurofilaments accumulate in neurons. Aluminum influences a number of neuronal processes, such as increasing protein synthesis and neurotransmitter breakdown, to decreasing neurotransmitter reuptake and slow axonal transport.
The present status of biological effects of toxic metals in the environment: lead, cadmium, and manganese
Authors: Shukla Girja S. , Singhal Radhey L.
Published: April 2011

The number of reports concerning the chemical toxicology of metals which are released in the environment by natural as well as anthropogenic sources, have been increasing constantly. Lead, cadmium, and manganese have found a variety of uses in industry, craft, and agriculture owing to their physical and chemical properties. The environmental burden of heavy metals has been rising substantially by smelter emission in air and waste sewage in water. Further, organic compounds of lead and manganese used as antiknock substances in gasoline are emitted into the atmosphere by automobile exhaustion. Such environmental contamination of air, water, soil, and food is a serious threat to all living kinds. Although these metals are known to produce their toxic effects on a variety of body systems, much emphasis has been placed on their effects on the nervous system owing to apparent association of relatively low or "subclinical" levels of metallic exposure with behavioral and psychological disorders. Clinical and animal data on environmental exposure show that while lead and manganese are most toxic to the nervous system, cadmium exerts profound adverse effects on kidney and the male reproductive system. It appears that the consequences of exposure to lead in adults are less severe than the types of exposure associated with hyperactivity in neonates. Except for a few reports, hyperactivity has indeed been observed in animals exposed to either of these three metals. Experimental work has also shown that these metals produce behavioral changes by altering the metabolism of brain neurotransmitters, especially catecholamines. Recently, it is hypothesized that these metals exert their toxic effect by damaging biological defences which exist in the body to serve as protective mechanisms against exogenous toxins. A voluminous publication list with diverse opinions on the biological effects of metals is available and there is an urgent need to compile assessment of the existing literature to identify the future theme of research work. The problem of metal toxicity becomes even more complex owing to simultaneous or successive exposure of the general population to different physical, chemical, biological, and psychological factors in the environment. The net toxic manifestations produced by multiple exposure should, therefore, be different from those produced by a single factor as the result of their additive, synergistic or antagonistic action. Even though a metal may not exist in sufficient amounts to cause any disability, the toxicity could result when a second factor is also present. Therefore, emphasis has been placed on developing an appropriate model which should not only evaluate the toxicity of a metal but also can serve as a predictive tool of toxic manifestations when encountered in combination with other factors. Further research work is required to unveil the primary initial event responsible for causing the various neurotoxic manifestations following exposure to metallotoxins.
Some observations on vinca alkaloid and ethanol neurotoxicity using dissociated neuronal cultures
Authors: Riopelle R. J. , Dow K. E. , Eisenhauer E.
Published: April 2011

Dissociated neuronal cultures have become a popular tool to address a number of questions in neurobiology. These culture systems may provide useful paradigms to approach problems related to in vivo neurotoxicity of xenobiotics. The clinical spectra of vinca neurotoxicity and alcohol teratogenesis is reviewed, and some observations on the use of dissociated cultures to study neuronal toxicity of vinca alkaloids and alcohol are presented.
Assessing safety of agricultural chemicals
Authors: Chen William L.
Published: April 2011

The objective of occupational health and safety programs in the chemical industry is to protect human health and the environment. Through studies in laboratory animals, bacteria, insects, and cultured cells, toxicologists collect data which allow them to predict which chemicals are likely to be hazardous to humans. The effects of acute (single high level exposures), subchronic (up to 6 months duration to sublethal levels), and chronic (lifetime to low level) exposures arc studied. Toxicity involving all organ systems is evaluated. Specific end points such as skin sensitization, birth defects, mutations, accumulation in tissues, carcinogenesis, and other toxic effects are evaluated. The data collected are used to provide information for forming guidelines regarding the safe manufacture, handling, use, and disposal of agricultural and other chemicals. The results of toxicology studies are also used to support the registration of products with government agencies in Canada and other countries.
Correlation between endogenous noradrenaline and glucose released from the liver upon hepatic sympathetic nerve stimulation in anesthetized dogs
Authors: Garceau Denis , Yamaguchi Nobuharu , Goyer Robert , Guitard Francine
Published: April 2011

The metabolic role of neurally released noradrenaline (NA) was studied in the liver of anesthetized dogs. Sustained stimulation with various frequencies was directly applied on the anterior plexus of hepatic nerves. Stimulation-induced changes in plasma concentrations of endogenous catecholamines in hepatic venous blood were determined in correlation with concomitant changes in those of glucose (GL). Mean basal values for hepatic venous NA, adrenaline, dopamine, and GL were 0.062, 0.022, 0.032 ng/mL, and 97.9 mg%, respectively. Among these catecholamines, NA was the only one being released significantly during stimulation. While hepatic venous NA increased rapidly during stimulation, being maximum within 3 min, hepatic venous GL increased gradually, reaching a maximum value 5 min after the onset of stimulation. A highly significant correlation (r = 0.90, P < 0.001) was found between changes in hepatic venous NA and GL concentrations observed during stimulation at various frequencies (2–16 Hz). However, hepatic vasoconstricting responses to stimulation were not correlated with increased hepatic venous GL. An α-blockade with phentolamine (2 mg/kg, iv) resulted in diminished release of GL by approximately 50% (P < 0.05) and reduced hepatic arterial vasoconstriction by approximately 47% (P < 0.01) upon stimulation (8 Hz, 5 min), even though NA release was markedly enhanced. We conclude that in the dog, NA is the sole catecholamine released within the liver in response to direct hepatic nerve stimulation, and NA thus released mediates the hepatic glycogenolysis via α-adrenoceptors.