bluuebunny/crossref_metadata_2025 huggingface dataset:
Lobster muscle and synapse respond to cortisol, a vertebrate hormone
Authors: Dixon D. , Atwood H. L.
Published: April 2011

Cortisol (0.28 μmol∙L−1) applied to lobster (Homarus americanus) neuromuscular preparations produces a hyper-polarization in muscle fibers and an increase in amplitude of excitatory postsynaptic potentials. The effect appears to be surface-mediated, because of its rapid onset (within seconds). It is also Na+–K+ ATPase dependent, because ouabain blocks the effects. The effects are relatively short-lasting, and gradually subside within 15 min. The increase in excitatory postsynaptic potentials is attributed in part to increased quantal output of transmitter, and not to changes in muscle fiber membrane resistance. The effects of cortisol on neuromuscular transmission and membrane potential indicate that cortisol may have a physiological role in crustaceans.
Role of norepinephrine in seizurelike activity of hippocampal pyramidal cells maintained in vitro: alteration by 6-hydroxydopamine lesions of norepinephrine-containing systems
Authors: Mody I. , Leung P. , Miller J. J.
Published: April 2011

Perfusion of 50 μM norepinephrine (NE) produced a marked, reversible decrease (range 20–28%) of the extracellular population spike and excitatory postsynaptic potential (EPSP) responses of the CA1 region evoked by stratum radiatum stimulation in the rat hippocampal slice preparation. The effects of NE were dramatically altered in slices obtained from animals which were previously treated with intracerebral or intraventricular injections of 6-hydroxydopamine (6-OHDA) to destroy forebrain catecholamine systems. In the latter preparations NE produced a reduction in the inhibition of the EPSP (50%), enhancement of the population spike amplitude, and multiple spike discharges characteristic of ongoing epileptiform activity. The reversal of NE-induced inhibition and the generation of seizurelike activity in 6-OHDA-treated animals suggests that NE may, in part, act upon interneurons to produce a disinhibition of CA1 pyramidal cells.
Characteristics of postsynaptic alpha1 and alpha2 adrenergic receptors in canine vascular smooth muscle
Authors: Curro Frederick A. , Greenberg Stan
Published: April 2011

A previous study suggested the existence of two distinct postsynaptic alpha adrenergic receptors in canine intralobar pulmonary arteries (IPA) and veins. The present study, performed using rings of canine IPA and dorsal metatarsal vein (DMV), was designed to characterize the factors affecting the postsynaptic alpha, and alpha2 receptors of these blood vessels. The responses of IPA and DMV to norepinephrine (NE), transmural nerve stimulation, phenylephrine (PE), guanabenz, and clonidine were obtained in the presence and absence of alterations in pH, extracellular calcium ion, sulfhydryl bond reduction and oxidation, and destruction of adrenergic nerves with 6-hydroxydopamine. The data demonstrate that: (i) α2-receptors are inactivated by changes in pH above or below pH 7.4, contain a labile disulfide group, are susceptible to modulation by increases and decreases in calcium ion, and appear to be decreased by destruction of adrenergic nerves; (ii) the NE and PE sensitive α1-receptors are insensitive to alterations in pH, refractory to disulfide reduction by dithiothreitol, slightly susceptible to modulation by calcium ion, and increased by destruction of adrenergic nerves. These data support the conclusion that the two subtypes of postsynaptic alpha adrenergic receptors differ in their properties and susceptibility to modification by alteration of the physiological environment.
Bicarbonaturic effect of acetazolamide in the dog: the Influence of graded volume expansion
Authors: Gougoux André , Vinay Patrick , Duplain Marcelle , Lanthier Diane , Cardoso Manuel , Lemieux Guy
Published: April 2011

Studies were performed in anesthetized dogs to characterize the effect of a progressive volume expansion on the acetazolamide-induced bicarbonaturia. A closed system with urine reinfusion was used in all these experiments. In normovolemic dogs, 24% of the filtered bicarbonate was excreted into the urine while this value reached 62% when a 10% expansion was superimposed on a continuous infusion of acetazolamide. When a single dose of acetazolamide was given, fractional bicarbonate excretion increased from 21% in normovolemic dogs to 46% during 10% expansion. Without acetazolamide administration, 13% of the filtered bicarbonate was excreted during a 10% expansion. The continuous infusion of acetazolamide in normovolemic dogs increased fractional bicarbonate excretion in a progressive fashion, from 25 to 40%. This study shows that an acute volume expansion potentiates markedly the bircarbonaturic effect of acetazolamide, fractional bicarbonate excretion exceeding by far the simple additive effect of acetazolamide and expansion. We speculate that volume expansion might prevent a compensatory rise in acetazolamide-insensitive bicarbonate reabsorption in sites other than the superficial proximal convoluted tubules.
Human female bladder and its noncholinergic contractile function
Authors: Cowan W. D. , Daniel E. E.
Published: April 2011

The response of human female detrusor muscle to field stimulation at varying voltages, durations, and frequencies was studied in vitro. In addition, the effects of adrenergic and cholinergic agonists and antagonists, and various nerve toxins were studied. Beta-adrenergic receptors were found in detrusor muscle but no significant adrenergic innervation was seen; no alpha-adrenergic receptors were seen. Atropine, scorpion venom, tetrodotoxin, beta bungarotoxin and hemicholinium were found to inhibit bladder contraction at short-pulse durations and low frequencies by approximately 50%. Black widow spider venom was seen to abolish bladder contractions entirely. It is concluded that acetylcholine is the neurotransmitter responsible for approximately 50% of bladder contraction. The remaining 50% would seem to be noncholinergic and not dependent on fast sodium channels for transmission of excitation, but would seem to be due to a structure with a short-membrane time constant, such as nerve, and is sensitive to black widow spider venom.
Changes in left ventricular dimensions and performance resulting from acute and chronic volume overload in the conscious dog
Authors: Belenkie Israel , Baumber John S. , Rademaker Alfred
Published: April 2011

A previously described animal model with an aorta to left atrium shunt has been modified to assess changes in left ventricular dimensions and performance resulting from volume overload of the left ventricle and to determine if any of these changes can predict outcome. In eight surviving dogs, end-diastolic and end-systolic diameters and estimated stroke volume increased rapidly in a curvilinear fashion over approximately 60 days with no significant changes thereafter. Mean normalized circumferential fibre shortening velocity was slightly less than and fractional shortening was similar to the controls; the changes in both indices were parallel to those in the controls. In five dogs that died 5–18 days postoperatively in congestive heart failure, none of the measurements obtained could be used to predict the outcome; the changes in the left ventricular diameters were similar to those in the survivors and systolic function was either normal or enhanced.
Calcium overload and strophanthidin-induced mechanical toxicity in cardiac Purkinje fibers
Authors: Lin Cheng-I , Vassalle Mario
Published: April 2011

In cardiac Purkinje fibers, strophanthidin increases and then decreases contractile force. The relationship between the decrease in force and calcium overload was studied by recording the electrical and mechanical activity under conditions known to increase calcium overload or its effects. Inhibitors of oxidative phosphorylation reduced the positive inotropy of strophanthidin and enhanced the decrease in force. These inhibitors also reduced the inotropic effect of high calcium. Increasing intracellular calcium by decreasing extracellular sodium concentration also resulted in a decrease in the strophanthidin inotropy. When arrhythmia was delayed, strophanthidin induced contracture and this was favored by blockers of glycolysis and by enhancing cellular calcium. Some of these effects were also observed in ventricular muscle fibers but at higher strophanthidin concentrations. The results suggest that the decline in contractile force during strophanthidin exposure is related to calcium overload, although it is made clear that in Purkinje fibers contractile force and resting force may be independently affected under suitable conditions.
Responses to ligation of a coronary artery in conscious rats and the actions of antiarrhythmics
Authors: Johnston K. M. , MacLeod B. A. , Walker M. J. A.
Published: April 2011

A method for ligating the left anterior descending coronary artery in conscious rats and measuring the resultant cardiovascular responses, arrhythmias, cardiac tissue loss, electrocardiogram (ECG), and mortality is described. Analyses of such responses identified statistically acceptable measures for which precision and interrelationships were defined. Responses to ligation were a variable function of the amount of ligated myocardial tissue. For example, arrhythmia score was a linear function of the square root of the occluded zone size. To test the ability of the model to detect beneficial drugs, verapamil, lidocaine, disopyramide, and quinidine were given. Low doses of verapamil (0.2 mg/kg i.v. + 0.3 mg∙kg−1∙h−1), and of disopyramide (10 mg/kg) had few antiarrhythmic, or other actions, whereas high doses of verapamil (20 mg/kg) and disopyramide (40 mg/kg i.v. repeated) were markedly antiarrhythmic as measured by all indices. Quinidine (20 mg/kg i.v. repeated) was also antiarrhythmic but less so than high dose disopyramide and verapamil. Lidocaine (10 mg/kg i.v. + 5 mg∙kg−1∙h−1) reduced the incidence of ventricular flutter and fibrillation. High-dose verapamil and quinidine, but not disopyramide, increased the number of nonarrhythmic deaths and the incidence of atrioventricular conduction defects.
Placental calcium and phosphorus transfer in the guinea pig: lack of effect of modulators of Ca-ATPase and alkaline phosphatase activity
Authors: McKercher H. G. , Derewlany L. O. , Radde I. C.
Published: April 2011

The effects of modulators of Ca-ATPase and alkaline phosphatase (AP) activity on placental calcium and phosphorus transfer were studied using the in situ perfused guinea pig placenta. The diuretics ethacrynic acid and furosemide had no significant effect on placental calcium and phosphorus transfer when injected into the mother (1.0 or 10.0 mg∙kg−1) or added to the solution perfusing the fetal side of the placenta (0.25 or 2.0 mM). These two drugs have previously been shown to inhibit placental Ca-ATPase and enhance AP activity in vitro. D-Penicillamine, which inhibits placental AP but not Ca-ATPase activity in vitro, also had no significant effect on net calcium and phosphorus transfer from mother to fetus either when given to the mother (50 mg∙kg−1) or added to the placental perfusion solution (0.25 or 2.0 mM). These results suggest that placental transfer of calcium and phosphorus in the guinea pig may not be directly related to placental Ca-ATPase and AP activities.
Distribution of radioactive silver in the subcellular fractions of various tissues of the rat and its binding to low molecular weight proteins
Authors: Matuk Yousef
Published: April 2011

In view of the electron microscopic evidence that silver does not penetrate cellular barriers, the distribution of radioactive silver in rat blood and subcellular fractions of liver, kidneys, spleen, and forebrain was studied. It was found that 24 h after a single intraperitoneal injection high levels of radioactivity were reached which decreased at different rates in the various tissues studied. In plasma, liver, and kidneys there was an initial rapid loss of radioactivity which was followed by a slower rate of loss. In the blood, forebrain, and spleen the loss of radioactivity was linear and somewhat slower than in the other three tissues. The cytosols of the liver and kidneys contained 60% while those of the forebrain and spleen contained 30% of the total radioactivity found in the tissue homogenates. Gel filtration on Sephadex G-75 showed that all cytosols contained two peaks of radioactivity; a high molecular weight peak which eluted just after the void volume and a low molecular weight peak. The amount of radioactivity in both peaks was, however, much lower in the chromatographic peaks of the forebrain and spleen than that found in those of the liver and kidneys. Furthermore, the spleen had a comparatively very small low molecular weight radioactive peak. In vitro experiments with liver cytosol showed similar results to those found in vivo in that the high molecular weight radioactive peak could be removed by heat. It is concluded that silver does enter cells and that silver thionein exists in the cytosols of forebrain, spleen, kidney, and liver.
Influence of adenosine triphosphate on the isolated perfused mesenteric artery of the rabbit
Authors: Krishnamurty V. S. R. , Kadowitz P. J.
Published: April 2011

The vascular effects of adenosine triphosphate (ATP) were examined in the isolated perfused mesenteric arteries of the rabbit. Bolus injections of ATP (1 × 10−8 to 10−6 mol) induced a dose-dependent vasoconstrictor response at resting perfusion pressure, while continuous perfusion with ATP briefly elicited a vasoconstrictor response which was not maintained. Perfusion with phentolamine (2.65 × 10−6 M, an α-adrenergic receptor blocker), indomethacin (8.37 × 10−6 M, an inhibitor of cyclooxygenase), atropine (1 × 10−7 M, a muscarinic receptor blocker), and hydralazine (2 × 10−4 M, a vascular smooth muscle inhibitor) for a period of 1 h had no effect on vasoconstrictor responses to ATP. However, pretreatment with reserpine (2 mg∙kg−1∙day−1 for 2 days), an agent which depletes catecholamines, potentiated responses to ATP. On the other hand, when vascular tone was increased with an isoosmotic 60 mM K+ depolarizing Krebs bicarbonate solution, bolus injections of ATP elicited a prominent dose-dependent vasoconstriction followed by a prominent vasodilation. The degree of vasodilation but not of vasoconstriction elicited by ATP was greater in small terminal arteries with branches (<0.5 mm outside diameter (o.d.)) than in the medium size arteries (≤1 mm o.d.) without terminal branches. Both the vasoconstrictor and vasodilator responses were unaffected by a perfusion with atropine, indomethacin, or eicosatetraynoic acid (ETYA, 1 × 10−4 M) for 1 – 2 h. The vasoconstrictor responses were potentiated while the vasodilator responses were inhibited significantly by perfusion with propranolol (3 × 10−6 M) and phentolamine (2.65 × 10−6 M) together for 1 h or by pretreatment with reserpine followed by cold storage at 2 °C for 24 h. Perfusion with 8-phenyltheophylline (4 × 10−6 M (8-PT), an adenosine receptor blocker) for 1 h significantly inhibited by the vasodilator responses to bolus injections of adenosine but not to ATP. Further, ATP but not adenosine elicited a much more prominent vasodilator response on norepinephrine (NE) induced tone than on 60 mM K+. These studies suggest that ATP may induce vasoconstriction independent of activation of α-adrenergic or muscarinic receptors or enhanced synthesis of prostaglandins. This vasoconstriction is resistant to the inhibitory influence of hydralazine. On the other hand, the vasodilator response to ATP may be mediated through its interactions with released or circulating norepinephrine.
Nucleoside transport in heart: species differences in nitrobenzylthioinosine binding, adenosine accumulation, and drug-induced potentiation of adenosine action
Authors: Williams Evan F. , Barker Philip H. , Clanachan A. S.
Published: April 2011

The site-specific binding of the potent and selective nucleoside transport inhibitor, [3H]nitrobenzylthioinosine (NBMPR), to the nucleoside transport system of cardiac membranes of several species was investigated. The affinity of [3H]NBMPR for these sites ranged from 0.03 nM in rat to 0.78 nM in dog. The maximal binding capacity of cardiac membranes for [3H]NBMPR was also species dependent and was greatest in bovine and guinea pig heart (2551 and 1700 fmol/mg protein, respectively) and least in rat (195 fmol/mg protein). The affinities of recognized nucleoside transport inhibitors and benzodiazepines for these transport inhibitory sites in guinea pig and rat heart were estimated by studying the inhibition of the site-specific binding of [3H]NBMPR in competition experiments. These values were compared with their inhibitory effects on the transporter-dependent accumulation of [3H]adenosine in guinea pig and rat cardiac muscle segments and with their ability to potentiate the negative inotropic action of adenosine in electrically driven guinea pig and rat left atria. In guinea pig heart, the recognized nucleoside transport inhibitors and benzodiazepines had an order of affinity (dilazep > hydroxynitrobenzylthioguanosine > dipyridamole > hexobendine [Formula: see text] lidoflazine [Formula: see text] flunitrazepam > diazepam > lorazepam > flurazepam) for the NBMPR site which was similar to those for the inhibition of [3H]adenosine accumulation and for potentiation of adenosine action. In contrast, in rat heart, where the maximal binding capacity of [3H]NBMPR was lower (eightfold), the nucleoside transporter dependent accumulation of [3H]adenosine was also lower (sixfold) and the negative inotropic action of adenosine was not significantly potentiated. Furthermore, NBMPR sites in rat heart displayed a significantly lower affinity for hexobendine, dipyridamole, and lidoflazine relative to sites in guinea pig hearts. These data indicate that significant differences in cardiac nucleoside transport systems exist among species with respect to both membrane density and drug affinity. Such differences influence the ability of transport inhibitors to modify adenosine action in these tissues.
Effect of enalapril (MK-421), an orally active angiotensin I converting enzyme inhibitor, on blood pressure, active and inactive plasma renin, urinary prostaglandin E2, and kallikrein excretion in conscious rats
Authors: Schiffrin Ernesto L. , Gutkowska Jolanta , Thibault Gaétan , Genest Jacques
Published: April 2011

The angiotensin I converting enzyme (ACE) inhibitor enalapril (MK-421), at a dose of 1 mg/kg or more by gavage twice daily, effectively inhibited the pressor response to angiotensin I for more than 12 h and less than 24 h. Plasma renin activity (PRA) did not change after 2 or 4 days of treatment at 1 mg/kg twice daily despite effective ACE inhibition, whereas it rose significantly at 10 mg/kg twice daily. Blood pressure fell significantly and heart rate increased in rats treated with 10 mg/kg of enalapril twice daily, a response which was abolished by concomitant angiotensin II infusion. However, infusion of angiotensin II did not prevent the rise in plasma renin. Enalapril treatment did not change urinary immunorcactive prostaglandin E2 (PGE2) excretion and indomethacin did not modify plasma renin activity of enalapril-treated rats. Propranolol significantly reduced the rise in plasma renin in rats receiving enalapril. None of these findings could be explained by changes in the ratio of active and inactive renin. Water diuresis, without natriuresis and with a decrease in potassium urinary excretion, occurred with the higher dose of enalapril. Enalapril did not potentiate the elevation of PRA in two-kidney one-clip Goldblatt hypertensive rats. In conclusion, enalapril produced renin secretion, which was in part β-adrenergically mediated. The negative short feedback loop of angiotensin II and prostaglandins did not appear to be involved. A vasodilator effect, apparently independent of ACE inhibition, was found in intact conscious sodium-replete rats.
Regional distribution of free and sulfoconjugated catecholamines in the bovine adrenal cortex and medulla
Authors: Racz Karoly , Buu Nguyen T. , Kuchel Otto
Published: April 2011

The intraadrenal distribution of free and sulfoconjugated catecholamines and the activity of the catecholamine sulfoconjugating enzyme phenolsulfotransferase in the bovine adrenal gland are described. In the adrenal cortex all three free catecholamines, epinephrine, norepinephrine, and dopamine, were detected in various concentrations. In the adrenal medulla, the relative proportion of the main adrenal catecholamines, free epinephrine and free norepinephrine, was found to be higher in the medullary sections derived from the subcortical areas where the ratio of epinephrine to norepinephrine was 8:1 than in the centre of the organ where norepinephrine levels reached those of epinephrine. Free dopamine, representing about 1.0% of the total catecholamine content was distributed in the same pattern as epinephrine or the sum of epinephrine and norepinephrine, revealing a significant positive correlation between regional dopamine and epinephrine plus norepinephrine (r = 0.97) as well as between dopamine and epinephrine (r = 0.96). Phenolsulfotransferase activity was present in both medulla and cortex. Dopamine sulfate was detected in relatively small concentration in all cortical and medullary layers, but norepinephrine sulfate and epinephrine sulfate were not present. The meaning of this distribution of individual catecholamines and phenolsulfotransferase activity in both cortex and medulla is discussed.
Can exercise promote revascularization in the transition zone of infarcted rat hearts?
Authors: Przyklenk K. , Groom A. C.
Published: April 2011

A border or transition zone, comprising muscle fibers supplied by fewer capillaries than normal, and characterized by an altered capillary – fiber geometry, is present as long as 5 weeks following coronary artery occlusion in the rat. This zone, which extends 225 – 525 μm laterally from the margin of the necrosis, may be at risk of becoming hypoxic, especially under conditions of increased oxygen demand. Our objective was to determine whether exercise can stimulate capillary growth in this transition zone. Myocardial infarcts were induced in rats by ligating the left coronary artery, midway between its origin and the apex of the heart. After a 1-week recovery period, the animals underwent 4 weeks of voluntary exercise, 2 h/day, 6 days/week. Rats which had run a total distance of 5 – 10 km during the month had both a normal number of capillaries and normal capillary–fiber geometry in the transition zone. In contrast, rats that ran either less than 5 km or more than 10 km during the 4 weeks showed no significant improvement in the number of capillaries or capillary – fiber geometry within the border zone. Thus, under certain conditions, exercise can promote revascularization in the transition zone of infarcted rat hearts.
Subacute endotoxemia in dogs with experimental cirrhosis and ascites: effects on kidney function
Authors: Levy Mortimer , Wexler Marvin J.
Published: April 2011

To study the effect of low-grade continuous endotoxemia in normal and cirrhotic dogs, osmotic minipumps were filled with Escherichia coli endotoxin, implanted subcutaneously and arranged so that the endotoxin could be infused intravenously over a 7-day period in doses ranging from 2.5 to 100 μg/h. Observations were made at 3 and 7 days postinfusion. In normal dogs (N = 9), there was no effect on cardiac output or arterial pressure when doses as high as 50 μg/h were delivered into the circulation. Neither was there an effect on inulin or p-aminohippurate (PAH) clearances. At doses of 100 μg/h, dogs suffered a marked decrement in cardiac output, blood pressure, and renal perfusion and became lethargic at 3–7 days. In cirrhotic dogs, doses of 25 μg/h which had no effect in the control dogs, caused a significant decline in the glomerular filtration rate (59 – 21.5 mL/min) and CPAH (147 – 66 mL/min) at a time when cardiac output and blood pressure remained normal. At doses of 50 μg/h, cardiac output and blood pressure declined markedly and the dogs deteriorated quickly following 3 – 5 days of endotoxin. When endotoxin (25 μg/h) was given to dogs with acute biliary obstruction (serum bilirubin = 9.8 ± 0.1 mg/dL) or to dogs with chronic thoracic caval constriction (which produced portal hypertension and ascites), no effect was observed on either central hemodynamics or renal perfusion. The selective renal vasoconstrictor effect observed in cirrhotic dogs could not be abolished by intravenous phentolamine or propranolol, inhibitors of alpha- and beta-adrenergic activity, respectively. We conclude that continuous access of endotoxin to the circulation is a cause of selective renal vasoconstriction in the cirrhotic, but not the normal dog.
Renal function in rats with innervated and denervated kidneys before and during sodium pentobarbital anesthesia
Authors: Mercer P. F. , Kline R. L.
Published: April 2011

We have used a model for measuring renal clearances in the undisturbed rat to assess the role of the renal nerves in the depression of renal function during sodium pentobarbital anesthesia. One group of rats was studied with renal nerves intact and a second group was studied 7 – 9 days after bilateral renal denervation. Rats were prepared by placement of cannulae an average of 5 days prior to the clearance experiments. Renal function was measured before and after the injection of saline as the control vehicle and 2 – 3 days later, before, and after the injection of sodium pentobarbital (50 mg/kg) in the same rat. Sodium pentobarbital produced comparable decreases in glomerular filtration rate, para-aminohippuric acid clearance, urine flow rate, and sodium excretion in rats with denervated or innervated kidneys, injection of saline resulted in no differences in measured variables between the rats with intact or sectioned renal nerves. Sodium pentobarbital caused a drop in arterial pressure in the denervated group but not in the innervated group. In a second series of experiments rats with denervated kidneys were implanted with an inflatable occluder around the aorta. This occluder was inflated to limit the drop in arterial pressure during anesthesia. When the blood pressure to the kidneys was maintained, renal function did not decrease during sodium pentobarbital anesthesia. These experiments suggest that the renal nerves are involved in the decrease in renal function during sodium pentobarbital anesthesia.
Electrophysiological actions of histamine
Authors: Geller H. M. , Springfield S. A. , Tiberio A. R.
Published: April 2011

This paper reviews data which illustrate that histamine has prominent actions on the electrophysiology of mammalian central neurons. Extracellular recordings reveal that this amine can either excite or depress neuronal activity in different regions of the brain. The excitations are associated with activation of H1 histamine receptors, whereas depressions are associated with occupancy of H2 receptors. Intracellular experiments have revealed multiple actions of histamine on membrane potential and conductance as well as on amplitude and frequency of postsynaptic potentials. In addition, we present preliminary data from rat cerebral cortex and hippocampal slices which suggest a modulatory role for histamine on γ-aminobutyric acid mediated neurotransmission in the areas of the brain.
Recent advances in histamine research: Closing remarks
Authors: Cook D. A.
Published: April 2011

In an attempt to highlight some of the more interesting problems of current histamine research several issues have been considered, including the difficulty of finding selective drugs, particularly agonists, the problems of receptor and organ selectivity, and the mystery of the biological function of histamine receptors in smooth muscle. These problems were raised in one form or another by speakers at this symposium and it is clear that despite the many exciting advances reported in the earlier communication many mysteries remain.
Chronic treatment with [D-Ala6, des Gly-]-LHRH ethylamide reversibly delays puberty in the female rat
Authors: Landymore Kathleen M. , Wilkinson Michael
Published: April 2011

Luteinizing hormone-releasing hormone (LHRH) agonist analogs have been suggested as a useful treatment for precocious puberty, though there is some concern that long-term treatment might be deleterious to normal sexual development. We have taken advantage of the very short maturation period of the female rat (approximately 35 days from birth) to examine the effects of chronic (daily) treatment with [D-Ala6, des Gly-[Formula: see text]]-LHRH ethylamide. We have observed that this treatment (either 1 or 2 μg/day) from day 5 after birth significantly delays sexual maturation but does not affect subsequent sexual cycles.
Redox state of brown adipose tissue as a possible determinant of its blood flow
Authors: Ma Stephanie W. Y. , Foster David O.
Published: April 2011

During norepinephrine (NE) induced thermogenesis in the adipocytes of brown adipose tissue (BAT), the blood flow of the tissue, and thus its oxygen supply, seems to be controlled by the adipocytes, possibly through their production of a vasodilator. This study sought to discover a metabolic parameter of the adipocytes that might account for modulation of vasodilator production and BAT blood flow. The blood flow of the interscapular BAT (IBAT) of anesthetized, cold-acclimated rats was varied by infusing NE and by altering the concentration of oxygen in arterial blood [Formula: see text]. Flow was measured with radiolabeled microspheres. IBAT was freeze fixed in situ for determination of its levels of adenine nucleotides and its cytosolic redox state; the latter was measured in terms of the concentration ratios, lactate/pyruvate (L/P) and glycerol-3-phosphate/dihydroxy-acetone phosphate (GP/DHAP) in the tissue. The increase in IBAT blood flow with dose of NE was associated with a progressive decline in tissue ATP, increases in ADP and AMP at high doses of NE, and progressive increases in L/P and GP/DHAP, the latter increases indicating increased reduction of the cytosolic NAD+–NADH system. Reducing [Formula: see text] by hemodilution raised the blood flow, L/P, and GP/DHAP of IBAT to values significantly above those measured in rats of normal [Formula: see text] given the same doses of NE; whereas, elevating [Formula: see text] by hemoconcentration had the opposite effects on these values. For rats of normal or altered [Formula: see text] together, a correlation coefficient of 0.94 was obtained for the relation between IBAT blood flow and L/P and one of 0.85 for that between flow and GP/DHAP. The coefficients for these relations were 0.98 when data from rats of normal [Formula: see text] only were used. Changes in the levels of ATP, ADP, and AMP or in the ratios of these nucleotides in IBAT did not correspond well with changes in blood flow. The results indicate that the cytosolic redox state of BAT may be the metabolic parameter underlying the control of BAT blood flow.
Management of toxic substances and hazardous wastes
Authors: Niemela V. E.
Published: April 2011

This paper describes the extent of the hazardous and toxic chemical waste problems in Canada and discusses the management, treatment, and disposal methods commonly used in North America and Europe. The treatment and disposal techniques covered are biological, physical–chemical, incineration technologies, and secure land disposal. Some of the available and emerging technologies for destruction of polychlorinated biphenyls are also described.
Regression of isoproterenol-induced cardiac hypertrophy
Authors: Tang Qian , Taylor Paul B.
Published: April 2011

Cardiac hypertrophy was induced in adult female Wistar rats after 8 days of daily subcutaneous injections of isoproterenol (ISO). Regression from hypertrophy was studied following 1, 2, 4, 8, 12, and 20 days of ISO withdrawal. After 8 days of treatment cardiac mass increased 40%. Following ISO withdrawal, ventricular regression occurred during the first 8 days. After 12–20 days of recovery, a new steady-state heart weight to body weight ratio was established that was 12–13% above the controls. The half-time recovery for heart weight was 3.8 days. Ventricular RNA content was stimulated 76% after 8 days of ISO-induced hypertrophy. During regression RNA content decreased rapidly during the first 8 days with a half-time of 3.4 days. Following 20 days of recovery ventricular RNA was still 31% above the controls. However, myocyte RNA was stimulated 86% following 8 days of ISO treatment and returned to control level after 12 days of regression. Myocardial DNA was increased 23% in the hypertrophied hearts and did not change during the recovery period. Hydroxyproline was increased in the ISO-treated hearts and decreased only slightly during the recovery interval. These data indicate that ISO-induced hypertrophy was reversible while ventricular RNA content only partially recovered. Nevertheless, myocyte RNA showed a large stimulation that was completely reversible at least after 12 days of recovery.
Inhibition of prostaglandin synthesis by ovine allantoic fluid: acute reduction in inhibitory activity during late gestation
Authors: Harper Catherine M. Leach , Thorburn G. D.
Published: April 2011

The capacity of ovine allantoic fluid to modulate prostaglandin (PG) synthesis was measured in fluid taken from ewes at 100–140 days gestation. An inhibitor of PG synthesis was found in allantoic fluid from ewes at 100–130 days gestation. The inhibitor had the capacity to inhibit PGF2α, PGE2, and 6-keto-PGF1α synthesis by endometrial cotyledon microsomes in a concentration-dependent manner. At 140 days gestation, the inhibitory potency of the fluid was significantly less than that present at 100–130 days gestation, at concentrations greater than 20% (v/v) (p < 0.001). The inhibitor is not albumin and remained active after boiling, dialysis, and protease treatment. It was extracted with chloroform–methanol, indicating that the active portion of the molecule is a lipid. We suggest that parturition in the sheep may be associated with a local withdrawal of inhibition of prostaglandin synthesis.
Pharmacological properties of canine intrapulmonary blood vessels
Authors: Kong Siow-Kee , Stephens Newman L.
Published: April 2011

The contractile response of ring segments of large, medium, and small pulmonary arteries and veins of the dog to histamine, norepinephrine, and serotonin have been studied. The maximum contractile response to these drugs was normalized with respect to the maximal response obtained in stimulation with 127 mM K+. The small pulmonary artery was more reactive to histamine, norepinephrine, and serotonin when compared with large and medium pulmonary arteries. The medium and large pulmonary artery showed no difference in reactivity to histamine. However, the mean effective dose (ED50) values for these agonists among the different segments of pulmonary arteries showed no significant difference. The small and medium pulmonary veins demonstrated increased reactivity to histamine, but not to norepinephrine and serotonin. The ED50 values also indicated that both small and medium veins were more sensitive to histamine when compared with the large pulmonary vein. The log concentration percent response curves for both small and medium pulmonary veins were displaced leftward (increased sensitivity) with respect to that for the large pulmonary vein. However, the reactivity and sensitivity to histamine between medium and small pulmonary veins were no different. The reactivity and sensitivity of different segments of pulmonary veins to norepinehrine and serotonin showed no significant differences among them. We conclude that histamine and other vasoactive substances, which are directly or indirectly related to mast cell degranulation, exert pharmacological effects on the pulmonary vasculature which possesses differential responsiveness at various levels of the vascular tree.
A comparison of the effects of cationic, anionic, and neutral amphipathic agents on the contractile behaviour of frog skeletal muscle. I. Twitches and potential threshold for contraction
Authors: Foulks James G. , Morishita Lillian
Published: April 2011

Cationic, anionic, and neutral amphipathic agents displayed striking differences as well as similarities in their effects on the contractile function of frog skeletal muscle. Slowed repolarization during the action potential appeared to account for twitch potentiation by low concentrations of alkyl trimethylammonium and by small n-alkanols (propanol, butanol). Small n-alkanols also caused a decrease in the potential threshold for K contractures and slower relaxation of submaximum K contractures as well as enhancement of chloride withdrawal and caffeine contractures, but these effects were not observed with larger alkanols. For the ionic amphipathic agents, the direction of the changes in the relation between K0 and K-contracture tension could be accounted for on the basis of the expected changes in surface charge, but the effects of these two types of agents on the rate of relaxation of submaximum K contractures were disproportionate and with the cationic series were opposite in direction to those produced by inorganic divalent cations. The reductions in the amplitude of chloride-withdrawal contractures by cationic as well as anionic amphipaths indicated that both types of agents can impair excitation–contraction coupling. Similar depressant effects on caffeine contractures demonstrate that these responses also can be influenced by events restricted to the external lamina of the sarcolemma. It is concluded that opposite effects can be produced by similar perturbations in different regions of the sarcolemma and that electrostatic as well as hydrophobic interactions can make an important contribution to the effects of amphipathic agents on twitches and contractures in skeletal muscle.
Maternal and fetal ethanol pharmacokinetics and cardiovascular responses in near-term pregnant sheep
Authors: Cumming M. E. , Ong B. Y. , Wade J. G. , Sitar D. S.
Published: April 2011

The disposition and cardiovascular effects of ethanol were studied in near-term pregnant sheep and their fetuses after intravenous infusions either to the mother or the fetus. Placental transfer of ethanol from mother to fetus was rapid, but transfer from the fetal to maternal circulation was impaired when ethanol was administered directly to the fetus. Plasma clearance of ethanol was similar from the mother and fetus in utero. In the maternal infusion experiments, both maternal and fetal heart rate increased with plasma ethanol concentration. However, in the fetal infusion experiments, fetal heart rate was inversely related to plasma ethanol concentrations while maternal mean arterial blood pressure increased with maternal plasma ethanol concentration. Further studies in neonatal lambs are needed to determine if ethanol has adverse effects on hemodynamics when the neonate is separated from its protective intrauterine environment.
Preservation of ischemic myocardial tissue with an antagonist of vasoconstrictor eicosanoids
Authors: Lefer Allan M. , Burke Sandra E. , Lepran Istvan
Published: April 2011

A new antagonist of the vasoconstrictor eicosanoids, L-640,035, was studied in a standardized model of myocardial ischemia (MI) in anesthetized cats. This eicosanoid antagonist was not found to exert any overt hemodynamic action in cats subjected to a sham myocardial ischemia protocol. However, the antagonist markedly reduced the S-T segment of the electrocardiogram when administered 30 min after permanent occlusion of the left coronary artery. Moreover, circulating activities of the marker enzyme creatine kinase (CK) were markedly attenuated by L-640,035 3–5 h after the onset of MI. This was verified by cardiac biopsies 5 h post-MI since myocardial CK activities decreased much less in treated MI cats than in MI cats receiving only the vehicle for L-640,035 (i.e., ethanol). The active metabolite of the antagonist in biological fluids (i.e., L-636,499) markedly antagonized the vasoconstrictor actions of endoperoxide and thromboxane analogs, but not of noneicosanoids in isolated perfused coronary arteries.
Inhibition of pepsinogen secretion in isolated gastric glands by amphotericin B is secretagogue specific
Authors: Norris S. H. , Hersey S. J.
Published: April 2011

Pepsinogen secretion from isolated gastric glands, stimulated by 8-bromoadcnosine 3′,5′-cyclic monophosphate (8BrcAMP), forskolin, or cholecystokinin octapeptide, was inhibited by the presence of amphotericin B in the incubation medium. However, amphotericin had no effect, or only a slight effect (<10% inhibition), on pepsinogen secretion stimulated by crude secretin. Incubation of glands with either of the mitochondrial inhibitors, rotenone or carbonyl cyanide m-chlorophenylhydrazone, reduced pepsinogen secretory responses both to 8BrcAMP and to crude secretin. This suggests that amphotericin inhibition, which is secretagogue specific, was not the result of a general metabolic inhibition. Amphotericin caused an increase in sodium and chloride content and a decrease in potassium content of glands. Experiments in which the medium content of either sodium, potassium, or chloride was varied, suggested that part of the amphotericin inhibition could be attributed to a rise in intracellular chloride content. Results did not support the involvement of changes in intracellular sodium or potassium content in the inhibitory mechanism of amphotericin. It was concluded that amphotericin caused a rapid and secretagogue-specific inhibition of pepsinogen secretion in isolated gastric glands, and that the mechanism of inhibition may, to some extent, involve changes in intracellular chloride content.
Functional activity in the lateral habenular and dorsal raphe nuclei following administration of several dopamine receptor antagonists
Authors: Ramm Peter , Beninger Richard J. , Frost Barrie J.
Published: April 2011

2-[14C]deoxyglucose autoradiography was used to show regional functional activity in the rat brain following administration of the dopamine antagonists, cis-flupenthixol, metoclopramide, and pimozide. Elevation of functional activity was observed in the lateral habenula (LHb) following administration of all antagonists. The dorsal raphe nucleus (DR) exhibited decreased functional activity following cis-flupenthixol, which exerts effects at both the D1 and D2 receptors, but not following pimozide or metoclopramide, which primarily act at the D2 receptor. These results converge with previous reports suggesting that the functional status of the LHb is regulated by dopaminergic systems, and that LHb efferents may exert a major influence upon DR neurons. These data further suggest that an influence of the LHb upon DR neurons may be affected via the D1 receptor.
A novel therapeutic approach for reversal of left ventricular hypertrophy and blood pressure control in hypertensive patients treated with alpha-methyldopa or propranolol
Authors: Fernandez P. G. , Snedden W. , Kim B. K. , Lee C. C.
Published: April 2011

A recently added goal in the control of primary hypertension is the reversal of left ventricular hypertrophy which may occur early in the disease and which can have serious consequences. We have attempted to define the hemodynamic parameters which distinguish most sensitively between the long-term effects of two antihypertensive drugs, alpha-methyldopa and propranolol, with a view to determining the optimal conditions under which each of the drugs may be used therapeutically. Twenty matched hypertensive patients, all with established left ventricular hypertrophy, were divided at random into two groups who received either alpha-methyldopa or propranolol as monotherapy. Dosage was titrated until blood pressures were normalized (diastolic blood pressure (DBP) ≤ 95 mmHg) (1 mmHg = 133.322 Pa); then therapy was maintained for 48–52 weeks. Supine and erect blood pressures, heart rates, and eight echocardiographic indices were recorded before commencement of therapy and at the 48- to 52-week period. Stepwise discriminant analysis identified erect DBP, erect heart rate, and posterior wall thickness of the left ventricle as being the parameters which distinguished most clearly the therapeutic effects of the chosen drugs. Using these three parameters, all 20 patients were correctly classified into their respective drug groups. We propose that these results may form the basis of a more rational choice of antihypertensive therapy with alpha-methyldopa or propranolol for hypertensive patients based on the initial determination of these three parameters.
The in vitro effects of benzodiazepines on the rat diaphragm. Structure–activity relationships
Authors: Driessen Jacques J. , Egmond Jan Van , Vree Tom B. , Booij Leo H. D. J. , Crul Jan F.
Published: April 2011

The effect of three different subgroups of benzodiazepines on the indirectly evoked twitch tension was investigated in the in vitro rat phrenic nerve – hemidiaphragm preparation. Two effects were observed: an initial increase in twitch tension at lower concentrations with some benzodiazepines, and a concentration-dependent depression at higher concentrations with all benzodiazepines. Significant differences for these effects were observed among the three subgroups of benzodiazepines and additionally within the subgroup of the 1,4-benzodiazepine-2-ketones. Structural requirements for both effects were different. For the increase of twitch tension a —CH3 substitution at R1 and a —F substitution at R2′ were beneficial. For the twitch depression an —OH substitution at R3 and a —Cl substitution at R2′ were optimal. An interaction between substituents at different substitution sites occurred. The potency of twitch depression showed a good correlation with literature reports of pKa values and a poor-to-inverse correlation with lipophilicity indices. A benzodiazepine antagonist, Ro 15-1788, caused no change in twitch tension in the concentration range of the investigated benzodiazepines nor did it prevent the twitch depression caused by benzodiazepines.
Induction of premature delivery in sheep following infusion of cortisol to the fetus. I. The effect of maternal administration of progestagens
Authors: Jenkin G. , Jorgensen G. , Thorburn G. D. , Buster J. E. , Nathaniels P. W.
Published: April 2011

Premature induction of delivery in fetuses infused with graded doses of cortisol was brought about in 123.5 ± 7.7 h (mean ± SEM, n = 6) after the start of cortisol infusion. This treatment caused a rise in fetal plasma cortisol similar to that observed at normal delivery. Maternal and fetal progesterone and 20α-dihydroprogesterone concentrations decreased to basal levels during infusion of cortisol to the fetus. Induction of premature delivery was delayed or prevented by concomitant treatment of the ewe with progestagen. Maternal intramuscular injection of 100 mg progesterone, 2 times daily, prevented delivery in four of four ewes treated during the time that cortisol was infused into the fetus (11–13 days). Maternal plasma progesterone and 20α-dihydroprogesterone concentrations were maintained during this period, but fetal plasma progesterone concentrations decreased to the same extent as in the fetuses infused with cortisol alone. A single intramuscular injection of 250 mg of medroxyprogesterone acetate to ewes on the day before commencement of infusion of cortisol to the fetus prevented delivery in four of six ewes during the time that cortisol was infused for 9, 13, 14, and 15 days, respectively. One ewe delivered a live lamb at 133.5 h and another at 147.7 h after the start of infusion of cortisol to the fetus. Maternal and fetal plasma cortisol, progesterone, and 20α-dihydroprogesterone concentrations were similar to those observed during infusion of cortisol alone to the fetus. Although fetal cortisol concentrations rose in a similar fashion, and to a similar extent, in all three groups during infusion of cortisol to the fetus, fetal 11-desoxycortisol concentrations only rose above basal levels close to the time of delivery in cortisol-infused fetuses or, in the progestagen-treated groups, when the fetus showed signs of being stressed.