bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of methods used to assess dietary intake: simulation analyses
Authors: Beaton George H. , Chery Anne
Published: April 2011

The choice of dietary methodology can affect the ability to detect and describe the relationship between dietary sodium intake and blood pressure. This is illustrated in this paper through the use of simulation modelling of the effect of using different dietary methods (food recalls or records covering different numbers of days, food frequency questionnaire estimates of a single diet component) and using urinary excretion as a proxy for intake. Both epidemiologic studies and experimental interventions are simulated. Although the data base used was simulated rather than real, an attempt was made to keep it realistic in relation to what might be seen in actual populations. From these analyses it can be inferred that with appropriate choice of methodology and study design, even low order relationships between sodium intake and blood pressure should be detectable. At a more general level, it may be concluded that while there is no perfect dietary methodology, there are preferred methodologies for defined purposes.
Weight reduction in the management of hypertension: Epidemiologic and mechanistic evidence
Authors: Reisin Efrain
Published: April 2011

A number of studies have established a close association between increased body mass and elevated blood pressure. The presence of obesity in hypertensive subjects is associated with some hemodynamic, metabolic, and endocrinic characteristics: an increased intravascular volume with a high intracellular body water/interstitial fluid volume ratio, increased cardiac output, stroke volume, and left ventricular work while peripheral resistance was reduced or normal. Weight loss of at least 10 kg can reduce blood pressure independently of changes in sodium intake in obese persons of both sexes with mild, moderate, or severe high blood pressure. The fall in arterial pressure in obese hypertensives after weight loss may reverse many of the previously mentioned altered findings and underscore previous epidemiological studies that have shown that weight control could be an important measure in the treatment of hypertension.
Nutritional management of hypertension: past, present, and future
Authors: Genest Jacques
Published: April 2011

A succinct overview of the nutritional management of hypertension, past, present, and future is presented. Prior to 1945, the low sodium diet and the rice–fruit diet were shown to be effective in reducing the blood pressure to normal levels in 35–40% of hypertensive patients. Between 1945 and the present, many studies were made on the effects of alcohol, water hardness, obesity, moderate restriction of sodium with increased potassium intake, increased dietary calcium, low animal and high unsaturated fat intake, and increased amounts of fiber in the diet. Criticisms are made of the very small magnitude, even if statistically significant, of blood pressure decreases and the too-short control periods in many instances, and also concerning the assumption of use of 24-h urinary sodium as an accurate index of the sodium intake, and of urinary creatinine as a physiological reference standard against the excretion of sodium. The author mentions, for possible future research, long-term studies of the effects of diets moderately restricted in sodium and high in potassium, of reducing weight and increasing physical activity in obese hypertensives, and of low animal and high polyunsaturated fat diets in patients with mild essential hypertension.
Reduction in transmembrane Ca influx induced by the negative inotropic action of nicardipine in frog ventricular muscle
Authors: Hatae Junna
Published: April 2011

The effects of nicardipine, a new 1,4-dihydropyridine derivative, on electrical and mechanical properties of frog ventricular muscle were examined. Nicardipine (3 × 10−7 M) reduced the twitch tension, and this reduction was frequency dependent, and considerable, in case of high frequencies. The resting potential was not affected by nicardipine (3 × 10−7 M), but the plateau height of the action potential was decreased and the duration of the action potential was shortened. The suppression of this plateau height was frequency dependent. The nicardipine-induced suppression of tension and action potential could be almost completely antagonized by raising the concentration of [Ca]o or by applying isoprenaline (8 × 10−7 M). These results suggest that the negative inotropic action of nicardipine is induced mainly by a reduction in the transmembrane Ca influx.
Effects of inotropic agents on isolated guinea pig heart under conditions that modify calcium pools involved in contractile activation
Authors: Temma Kyosuke , Akera Tai , Ng Yuk-Chow
Published: April 2011

Positive inotropic effects of strophanthidin were compared with those of isoproterenol, BAY K 8644, grayanotoxin, veratridine, and monensin in electrically stimulated left atrial muscle preparations of guinea pig heart under conditions in which the calcium pool, playing a primary role in contractile activation, was altered. In concentrations that caused similar degrees of increase in developed tension under 1 Hz stimulation, grayanotoxin and strophanthidin caused a relatively large increase in potentiated postrest contraction compared with that caused by isoproterenol, whereas the effect of BAY K 8644 on the postrest contraction was the smallest. The effect of high concentrations of grayanotoxin or strophanthidin, however, resembled that of isoproterenol. The sensitivity of the isolated heart muscle to these agents was compared under conditions in which utilization of various calcium pools contributing to contractile activation was suppressed. Mn2+, which reduces contribution of very superficial Ca2+, reduced sensitivity of heart muscle to the positive inotropic effect of isoproterenol and enhanced the inotropic effect of monensin or veratridine. Verapamil, nifedipine, diltiazem, or ryanodine did not have marked effects on the positive inotropic action of Ca2+, monensin, veratridine, or strophanthidin. These results suggest that the positive inotropic actions of veratridine, grayanotoxin, and strophanthidin share a common mechanism and that low concentrations of strophanthidin may increase loading of Ca2+ pool, which plays an important role in potentiated postrest contraction.
Mise en évidence in vitro de la biosynthèse d'histamine à partir de carnosine par le rein de souris gravide
Authors: Arnould J. M.
Published: April 2011

Kidneys of pregnant mice synthesize histamine when incubated in the presence of carnosine, manganese, and pyridoxal phosphate. Intensity of biosynthesis increases linearly with the amount of enzyme and the incubation time. The reaction can only be catalysed by two enzymes that are located in kidneys and act in succession: carnosinase, which hydrolyzes carnosine into its two moieties, and histidine decarboxylase, which transforms histidine, a product of carnosine degradation, into histamine. The biosynthesis of histamine from carnosine seems to increase with the progress of pregnancy. In nonpregnant mice, kidneys do not effect this biosynthesis. The above results directly demonstrate that carnosine may be used for histamine synthesis when the activity of histidine decarboxylase is high, as in pregnant mouse kidney. Vertebrate carnosine, its role still enigmatic, might thus be mainly a potential histidine reservoir that would be mobilized any time there is a significant requirement for histidine, such as for histamine biosynthesis.
Tissue-specific concentration changes of estrone and estradiol during spontaneous and ACTH-induced parturition in sheep
Authors: Power S. G. A. , Challis J. R. G.
Published: April 2011

Changes in estrogen production are considered important in the sequence of events leading to parturition. We sought tissue-specific changes in the concentration of unconjugated estrone (E1) and estradiol (E2) in intrauterine fetal (amnion, chorion) and maternal (endometrium, myometrium) tissues during normal pregnancy, labour, and ACTH-induced labour in sheep. The mean concentrations of E1 and E2 in the fetal membranes were higher than in endometrium and myometrium. In amnion there were no consistent changes in estrone concentrations with gestation, although estradiol concentrations increased between day 130 and term. In the endometrium there were increases in both estrone and estradiol between day 100 and term, whereas in the myometrium increases in the concentrations of E1 and E2 occurred between days 130–135 and term. Animals showing a labourlike pattern of uterine contractions after intrafetal ACTH administration did not show significant differences in estrone or estradiol concentrations in amnion, chorion, or endometrium compared with saline-infused controls. However, there was a progressive increase in the concentration of estrone and estradiol in the myometrium during ACTH-induced labour. We conclude that changes in the concentrations of estrone and estradiol in intrauterine tissues vary between the tissues studied and the two estrogens. In general, estrogen concentrations increased towards term, but this trend was more marked in the maternal than fetal tissues. The changes in estrone concentrations in myometrium, but not in the other tissues, were replicated during ACTH-induced labour. Our results would be compatible with the suggestion that tissue-specific changes in estrogen concentrations may contribute to the local intrauterine steroid milieu during pregnancy and at term.
Prolonged isobaric relaxation time in small mesenteric arteries of the spontaneously hypertensive rat
Authors: Packer C. Subah , Stephens Newman L.
Published: April 2011

Prolonged isometric relaxation in hypertensive aortic and caudal arterial smooth muscle has been demonstrated; however, isobaric relaxation in resistance arteries is more pertinent to studies in hypertension. A comparative study of mesenteric arterial isobaric relaxation times was made using spontaneously hypertensive rats (SHR), normotensive Wistar–Kyoto rats (WKY), and MK-421 treated SHR (treatment commenced at 8 weeks of age and was maintained until sacrifice). Relaxation rates of vessels constricting against a range of pressures and achieving different degrees of narrowing or changes in circumference were analyzed. Comparisons were made between SHR, WKY, and MK-421 treated SHR arteries that had constricted from the same initial circumference and against the same magnitude of pressure. The SHR mesenteric arteries relaxed at a slower rate than did the WKY vessels. The normotensive MK-421 treated SHR showed the same prolonged relaxation rate as did the untreated SHR preparations. Thus the slower rate of relaxation in SHR arteries does not appear to be a consequence of the hypertension. Such prolonged time for narrowing would function to increase the average peripheral resistance and thus may contribute to the initiation and maintenance of increased blood pressure.
Comparative effects of metabolic inhibition on the action potential from three experimental models of cardiac cells
Authors: Yamamoto Tatsuo , Ruiz-Ceretti Elena , Schanne Otto F.
Published: April 2011

Because of conflicting reports on the basic mechanisms responsible for the action potential changes produced by hypoxia or metabolic inhibitors, we investigated the effect of 2,4-dinitrophenol, substrate deprivation, and 2-deoxy-D-glucose on three preparations of rat myocardium: adult and newborn ventricle and cultured cells derived from neonatal rats. The latter exhibit slow action potentials in contrast to the other two, which show fast action potentials. Cultured cells were insensitive to 2,4-dinitrophenol and substrate deprivation but were markedly inhibited by blocking of glycolysis. The action potential of adult cells was shortened in the three conditions tested but was most sensitive to blocking of oxidative phosphorylation, which abolished propagated electrical activity after 15 min of exposure. The response of newborn ventricle was intermediate between the other two. Our data indicated that as far as maintenance of the membrane electrical properties is concerned, the relative importance of different metabolic pathways varies with development after birth or with time in culture.
Noncholinergic contractile response to nicotine in the guinea pig isolated tracheal smooth muscle
Authors: Kizawa Yasuo , Takayanagi Issei
Published: April 2011

The existence of substance P immunoreactive nerves in the trachea of guinea pig is known. In this study, capsaicin induced a long-lasting and marked contraction in the guinea pig trachea and nicotine-induced contraction was partially reduced in the capsaicin-treated muscle. Furthermore, the contractile response to nicotine (10−5 M) in the presence of atropine (10−7 M) was abolished by a substance P antagonist, [D-Arg1, D-Pro2, D-Trp7,9 Leu11]substance P (10−5 M). These findings suggest that noncholinergic contractile response to nicotine may be due to the release of material(s) resembling substance P in the isolated tracheal smooth muscle preparation of guinea pig.
Mechanical factors regulating gastric emptying examined by the effects of exogenous cholecystokinin and secretin on canine gastroduodenal motility
Authors: Keinke O. , Ehrlein H. J. , Wulschke S.
Published: April 2011

The aim of the study was to elucidate the variables of gastroduodenal motility determining gastric emptying. For this purpose the effects of exogenous cholecystokinin, secretin, and gastric inhibitory polypeptide on motility and gastric emptying were studied during a meal. Motility was measured with extraluminal strain gage force transducers and induction coils in unanaesthetized dogs. The pyloric diameter and the duodenal lumen were evaluated from radiographs. Gastric emptying of an acaloric cellulose meal was determined radiographically. When compared with control infusion of saline, cholecystokinin (1.7 Ivy units∙kg−1∙h−1) and secretin (1.7 clinical units∙kg−1∙h−1) delayed gastric emptying and diminished the force of the antral contractions, the force and frequency of the duodenal contractions, and opening of the pylorus. The contractile patterns of the duodenum were changed from propulsive to segmenting activity. Cholecystokinin additionally diminished the duodenal lumen. In contrast, gastric inhibitory polypeptide (1.5 μg∙kg−1∙h−1) did not influence gastroduodenal motility and gastric emptying. It is concluded that the motility parameters that were significantly altered by cholecystokinin and secretin are involved in the control of gastric emptying, while other parameters that remained unchanged play a minor role in the regulating process.
Basal, oxytocin-, and insulin-stimulated glucose oxidation in human endometrium
Authors: Truchan B. , Taylor P. , Goren H. J. , Lederis K. , Hollenberg M. D. , Okabe T.
Published: April 2011

Samples of endometrium from regularly cycling women (28 ± 2 days cycle) were assayed for [U-14C]glucose oxidation activity in the presence or absence of 100 nM oxytocin or 1.7 nM insulin. The basal rate of glucose oxidation in the tissues obtained from women in early and midfollicular phase and late luteal phase was approximately 125 pmol/(h∙mg tissue). Late follicular and midluteal phases had higher basal rates, up to 400 pmol/(h∙mg tissue). Oxytocin increased glucose oxidation by 50–100 pmol∙h−1∙mg−1 in early and midfollicular phase and in early luteal phase endometrial fragments. Insulin did not stimulate glucose oxidation in these tissues. In samples of late luteal phase, glucose oxidation was stimulated by both oxytocin and insulin. High and low basal glucose oxidation activity in the endometrium corresponded, respectively, to reported periods of high and low plasma estradiol in normal menstruating women. In contrast, oxytocin stimulated glucose oxidation in endometria from women with anticipated low plasma estradiol.
Posttetanic changes in the afferent and efferent activity of monosynaptic reflex in kittens
Authors: Bawa Parveen
Published: April 2011

Both the afferent volleys from the dorsal root and the monosynaptic reflex discharges from the corresponding ventral root were recorded with hook electrodes during stimulation of the nerves innervating the triceps surae muscles. The effects of conditioning high frequency tetanus on the magnitudes of these afferents and reflex volleys were examined in kittens of postnatal age 1–90 days and in adult cats. In young kittens under barbiturate anaesthesia, large-amplitude monosynaptic reflex discharge can be evoked without prior conditioning. The amplitude of this reflex discharge decreased with increasing age of the animal. Application of conditioning tetanic stimuli to the muscle nerves resulted in posttetanic depression followed by posttetanic potentiation of the monosynaptic reflex. The magnitude of posttetanic depression was much higher than that of potentiation in the first postnatal week. As the age increased, the magnitude of depression decreased while the magnitude of potentiation increased. The afferent volley showed a considerable posttetanic potentiation in older kittens and cats. No significant potentiation or depression was observed in the younger animals. Possible mechanisms contributing to posttetanic depression and potentiation are discussed.
Barbiturate effects on hippocampal excitatory synaptic responses are selective and pathway specific
Authors: MacIver M. Bruce , Roth Sheldon H.
Published: April 2011

Barbiturate actions on excitatory synaptic responses in CA 1 and dentate regions of hippocampal slices were studied to determine whether different effects occur on anatomically distinct synaptic pathways. Pentobarbital facilitated transmission between stratum radiatum inputs and CA 1 neurons at low concentrations (0.02–0.08 mM) and produced postsynaptic depression at higher concentrations. Only depression was observed for stratum oriens inputs to CA 1 and perforant path inputs to dentate granulae neurons. The (+) isomer of pentobarbital was approximately four times more potent than the (−) isomer of racemic mixture. Phenobarbital (0.04–0.12 mM) produced only depression of synaptic responses in CA 1 and dentate pathways. Comparison of effect on field excitatory postsynaptic potentials and population spike responses indicated that the barbiturates act at selective and pathway-specific sites. The results provide further evidence for specific cellular and membrane recognition sites for barbiturate action.
Histamine as a Modulator of Airway Hyperreactivity L'histamine comme médiateur de l'hyperreactivité des voies aériennes
Authors: Burka John F.
Published: April 2011

Histamine has long been known as a bronchoconstrictor agonist, but its role in asthma and airway inflammation is not as clear. Histamine release occurs in response to allergic challenge of mast cells. However, it is now known that mast cells are heterogeneous in responsiveness and sensitivity to antiallergic agents. Other cells, such as alveolar macrophages, neutrophils, eosinophils, and lymphocytes, can also be activated during allergic and inflammatory reactions. Damage to the airway epithelium would reduce the release of an epithelium-derived relaxant factor and thus increase airway smooth muscle tone. Released mediators, including eicosanoids, platelet-activating factor (PAF), complement fragments, and neurotransmitters, also contribute to inflammation in the airways and the interaction of all these mediators complicates the interpretation of the role of individual mediators. Not only can individual mediators affect the biological activity of other mediators, but their synthesis and release can be modulated as well.The present symposium was organized to examine the putative role of histamine in airway hyperreactivity and how it might interact with other mediators. Papers were presented on the role of mast cells and epithelial cells in allergic bronchoconstriction. The interaction of mast cells with other inflammatory cells was also reviewed. Further information was presented on the biological characteristics of epithelium-derived relaxant factor. Other papers reviewed the interaction of mediators on bronchoconstrictor activity and in inflammation-induced changes in microvascular permeability. The speakers emphasized that asthma and other forms of airway inflammation are complex disease entities and that a systematic analysis of interactions between the cells and mediators in the airways is necessary to understand the aetiology of these diseases and to develop improved therapeutic regimens.This symposium was supported by the Pharmacological Society of Canada, the Canadian Histamine Association, the Upjohn Company of Canada, and Merck Frosst Canada Inc.
Diabetes alters the reactivity of myocardium to a thromboxane analogue
Authors: Canga Liliana , Gorelik Gabriela , Sterin-Borda Leonor
Published: April 2011

Atrial contractile response to U-46619 was studied in auricles from normal and acutely diabetic rats. U-46619 induced an increment of dF/dt in diabetic atria, whereas nondiabetic auricles elicited a negative contractile effect. Blockers of arachidonic acid metabolism via cyclooxygenase inhibited the stimulatory action of U-46619 in diabetic preparations. Moreover, inhibitors of thromboxane synthesis completely blocked the stimulatory effects of U-46619. The stimulant action of the thromboxane A2 mimetic was attenuated when diabetic auricles were incubated with lipoxygenase(s) blocking agents. Results suggest that in diabetic atria, the abnormal inotropic effect induced by U-46619 may be associated with thromboxane formation and with lipoxygenase(s) metabolites.
Properties of single Na+ channels in cut-open Myxicola giant axons
Authors: Schauf C. L.
Published: April 2011

Time- and voltage-dependent behavior of the Na+ conductance in dialyzed intact Myxicola axons was compared with cut-open axons subjected to loose-patch clamp of the interior and to axons where Gigaseals were formed after brief enzyme digestion. Voltage and time dependence of activation, inactivation, and reactivation were identical in whole-axons and loose-patch preparations. Single channels observed in patch-clamp axons had a conductance of 18.3 ± 2.3 pS and a mean open time of 0.84 ± 0.12 ms. The time-dependence of Na+ currents found by averaging patch-clamp records was similar to intact axons, as was the voltage dependence of activation. Steady-state inactivation in patch-clamped axons was shifted by an average of 15 mV from that seen in loose-patch or intact axons. Substitution of D2O for H2O decreased single channel conductance by 24 ± 6% in patch-clamped axons compared with 28 ± 4% in intact axons, slowed inactivation by 58 ± 8% compared with 49 ± 6%, and increased mean open time by 52 ± 7%. The results confirm observations on macroscopic channel behavior in Myxicola and resemble that seen in other excitable tissues.
Relationship of membrane systems in muscle to isomyosin content
Authors: Eisenberg Brenda R. , Dix David J. , Lin Zhaoying W. , Wenderoth Mary P.
Published: April 2011

The structures and functions of the various subdivisions of the membrane systems of muscle are reviewed. Morphometric data have been recalculated using functional definitions of the membranes as identified by their proteins. Thus, the junctional coupling between the sarcoplasmic reticulum and T system is separated from the remaining longitudinal sarcoplasmic reticulum that bears the calcium ATPase protein. In addition, the morphometry of the membrane systems is related to the various muscle fiber types as defined histochemically and by protein isoforms. The relation of isomyosin type and membrane quantities are compared for guinea pig, chicken, frog, and lobster skeletal muscles and rat and rabbit cardiac muscles. Fiber plasticity is considered in terms of the mixing and matching of amounts and kinds of membranes and proteins.
β-Adrenergic regulation of cardiac myosin
Authors: Winegrad Saul , McClellan George , Weisberg Andrea , Lin Lin Er , Weindling Steven , Horowits Robert
Published: April 2011

Calcium-independent regulation of the contractile proteins of cardiac muscle has been studied using hyperpermeable cells from rat ventricles and sections of quickly frozen rat hearts. These preparations have been used to study maximum calcium-activated force, myosin ATPase activity, and the maximum velocity of unloaded shortening. β-adrenergic activity increases the amount of force and the ATPase activity in accordance with the concentration of the V1 isozyme of myosin. V3 activity is decreased at the same time. In tissues containing only V1, there is no change in maximum velocity in response to β-adrenergic stimulation. These results indicate that β-adrenergic stimulation recruits V1 force generators and probably regulates a transition between a calcium unresponsive and a calcium responsive force generator.
Stimulation frequency and external ionic composition control the repriming of caffeine-induced contractures in frog skeletal muscle
Authors: Raymond Guy , Potreau Daniel , Cognard Christian , Jacquenod Jean-Claude , Poindessault Jean-Pierre
Published: April 2011

The effect of stimulation rate and of external ionic composition on the repriming period of contractures induced by 6 mM caffeine was tested on isolated skeletal muscle fibres of the frog (Rana ridibunda). The repriming period, which was 11.2 ± 0.1 min (mean ± SEM, n = 9) on quiescent fibres, was shortened in fibres stimulated at a frequency ranging from 3 to 12 min−1 (optimal rate, 8 min−1; full repriming 5.7 ± 0.2 min; n = 10). A 10-fold increase in the extracellular calcium concentration shortened the repriming period on both stimulated and quiescent fibres, whereas decreasing external calcium (1/10) delayed it. In a Na+-free solution (Li+ substituted) the repriming period of stimulated fibres was markedly delayed (14 min), whereas quiescent fibres never recover more than 10% of their ability to develop subsequent caffeine contractures. In contrast, with a 35% Na solution, the repriming period was greatly shortened (stimulated, 5.4 ± 0.2 min, n = 7; quiescent, 6.2 ± 0.5 min, n = 8). It is concluded that repriming depends on three mechanisms that seem to refill a calcium store and trigger recovery: the slow inward calcium current, a Na+–Ca2+ exchange, and perhaps a passive Ca2 influx.
Chronic dietary administration of tryptophan prevents the development of deoxycorticosterone acetate salt induced hypertension in rats
Authors: Fregly Melvin J. , Lockley Ora E. , Voort Judith van der , Sumners Colin , Henley William N.
Published: April 2011

Hypertension developed within 3 to 5 weeks in uninephrectomized rats administered deoxycorticosterone acetate (DOCA) at a dose of 850 μg∙kg−1∙day−1 via Silastic tubes and given isotonic saline to drink. Chronic dietary administration of tryptophan (25 and 50 g/kg of food) to DOCA-treated rats reduced their exaggerated intake of NaCl solution and attenuated the elevation of blood pressure induced by treatment with DOCA alone. Treatment with tryptophan also protected against the reduction in urinary concentrating ability during a 24-h dehydration that is characteristic of DOCA-treated rats. Other tests assessed the responsiveness to the β-adrenergic agonist, isoproterenol. These included measurement of drinking and heart rate following acute administration of isoproterenol. The characteristically depressed drinking and chronotropic responses of DOCA-treated rats to acute administration of isoproterenol were unaffected by tryptophan. Responsiveness to angiotensin II (AII) was also tested by assessment of dipsogenic and metabolic responses to acute administration of AII. The increased drinking and tail skin temperature responses to administration of AII, characteristic of DOCA-treated rats, were reduced in a graded fashion by treatment with graded doses of tryptophan. The specific binding of AII to its receptors in membranes from the diencephalon of the brain was increased by treatment with DOCA but was returned to control level by concomitant treatment with tryptophan. The content of serotonin in the mesencephalon of the brain was not changed significantly by treatment with tryptophan, but the content of 5-hydroxyindole acetic acid in the same region increased significantly, suggesting that turnover of serotonin was increased by chronic treatment with tryptophan. The cardiac hypertrophy characteristic of treatment with DOCA was attenuated significantly by chronic treatment with tryptophan, while the low, resting plasma renin activity of the DOCA-treated group was unchanged. These results suggest that tryptophan provides significant protection against the development of DOCA-induced hypertension, polydipsia, polyuria, and cardiac hypertrophy in rats. It also reduces the hyperresponsiveness to treatment with AII, possibly by decreasing the specific binding of AII to its receptors. It also appears to increase the turnover of serotonin in the brain. Whether either one or all of these is responsible for the antihypertensive effect of tryptophan remains for further study.
Effects of methylmercury on the spontaneous and potassium-evoked release of endogenous amino acids from mouse cerebellar slices
Authors: Reynolds J. N. , Racz W. J.
Published: April 2011

The effects of methylmercury on the spontaneous and potassium-evoked release of endogenous amino acids from mouse cerebellar slices have been examined. Methylmercury induced a concentration-dependent increase in the spontaneous release of glutamate, aspartate, γ-aminobutyric acid, and taurine from mouse cerebellar slices. Glycine release was slightly increased, but not in a concentration-dependent manner. The spontaneous release of glutamine from mouse cerebellar slices was not altered by any concentration of methylmercury examined (10, 20, and 50 μM). The tissue content of glutamate, γ-aminobutyric acid, glutamine, and taurine decreased after exposure to methylmercury. Exposure of cerebellar slices to 20 μM methylmercury resulted in a significant enhancement in glutamate release during stimulation with 35 mM K+. This increase could be accounted for by the methylmercury-induced increase in spontaneous glutamate release. The increase in spontaneous release of glutamate and γ-aminobutyric acid was independent of the availability of extracellular calcium. These results suggest that methylmercury increases the release of neurotransmitter amino acids, particularly γ-aminobutyric acid and glutamate, by acting at intracellular sites to increase release from a neurotransmitter pool. The increase in the potassium-stimulated release of glutamate may reflect an increased sensitivity of the cerebellar granule cell to the effects of methylmercury. It is suggested that alterations in amino acid neurotransmitter function in the cerebellum may contribute to some of the neurological symptoms of methylmercury intoxication.
Nonadrenergic modulation by clonidine of the cosecretion of catecholamines and enkephalins in adrenal chromaffin cells
Authors: Nguyen Tien T. , Léan André De
Published: April 2011

Cultured bovine chromaffin cells cosecrete catecholamines and enkephalins following cholinergic nicotinic stimulation. Initial reports on the inhibitory effect of clonidine on catecholamine secretion raised the possibility of a modulation of chromaffin cell function through a presynaptic adrenergic mechanism. The purpose of this work was to investigate the pharmacological characteristics of this inhibitory effect of clonidine on the cosecretion of catecholamines and enkephalins in 4-day-old cultured chromaffin cells. We observed that clonidine completely inhibits nicotine-stimulated secretion of both leucine-enkephalin and catecholamines with an IC50 of 34 μM. Treatment of chromaffin cells for 3 days with 100 nM reserpine leads to a 67% increase in nicotine-stimulated secretion of leucine-enkephalin without any effect on the IC50 of clonidine. In reserpine-treated chromaffin cells, norepinephrine (100 μM) inhibits only by 27% nicotine-stimulated secretion of leucine-enkephalin with an IC50 of 50 μM. Neither the alpha2-adrenergic antagonist yohimbine nor the alpha1-adrenergic antagonist prazosin could fully reverse the inhibitory effect of clonidine on leucine-enkephalin secretion at 10 nM. These results tend to rule out the role of alpha-adrenergic receptors in the mediation of clonidine inhibition of cosecretion in chromaffin cells.
Effect of Bay K 8644 on tetraethylammonium-induced excitability of the rabbit pulmonary artery
Authors: Ousterhout Julia M. , Sperelakis Nick
Published: April 2011

The effect of Bay K 8644 on the electrical activity of the smooth muscle cells in the main pulmonary artery of the rabbit was examined. In normal physiological solution, the resting membrane potential was −56 ± 0.6 mV, and the cells were electrically quiescent. Tetraethylammonium (5 mM) depolarized the membrane to about −45 mV, and electrical stimulation elicited action potentials. To suppress contractile responses and thereby facilitate sustained impalements, the muscle strips were bathed with a hypertonic solution containing sucrose. The mean amplitude of the tetraethylammonium-induced action potentials in the hypertonic solution was 35 ± 0.9 mV. The action potentials were dependent upon the extracellular Ca2+ concentration and were abolished by diltiazem (10−6 M). Spontaneous action potentials were occasionally generated in the presence of tetraethylammonium alone and could be induced by the further addition of Ba2+ (0.5 mM). The Ca2+ agonist Bay K 8644 (10−8 to 10−6 M) had no effect on the resting membrane potential or excitability in normal solution. However, in the hypertonic solution containing tetraethylammonium, Bay K 8644 caused a further depolarization and oscillatory potential changes, which were not prevented by tetrodotoxin. The oscillations were suppressed or abolished by diltiazem or nilvadipine. Thus, active responses can occur in the normally quiescent smooth muscle cells of the rabbit pulmonary artery when the outward K+ current(s) are suppressed.
Cell contamination due to the use of carrier-based microelectrodes
Authors: Oesch Urs , Ammann Daniel , Simon Wilhelm
Published: April 2011

When using microelectrodes for intracellular ion activity studies, some uncertainties such as interference from cytosolic components at the microelectrode, cell damage, and cell contamination may arise. A model, which treats kinetic processes of the loss of carriers from the membrane phase of microelectrodes into the cytosol and cell membrane, is used for an estimation of the extent and time course of contamination by impaled ion-selective microelectrodes. An isolated model cell consisting of a plasma membrane surrounding a cytosolic milieu is assumed. The results of its considerations represent a worst case situation, in which significant contamination of the cell membrane of such a small isolated single cell might occur during time periods of electrophysiological experiments. In more complex situations, such as in intact tissues, the equilibrium membrane concentrations may be substantially less.
Changes in the intracellular free calcium concentration of Aplysia and leech neurones measured with calcium-sensitive microelectrodes
Authors: Deitmer Joachim W. , Eckert Roger , Schlue Wolf-R.
Published: April 2011

The intracellular free Ca concentration was measured in invertebrate neurones using single-barrelled and double-barrelled neutral-carrier microelectrodes. The electrodes were calibrated in solutions containing different Ca concentrations between 1 mM and 0.01 μM. The electrode responses were also tested at different ionic strengths and at varying Na concentrations. The electrodes responded with 25–30 mV per 10-fold change in Ca concentration between 1 mM and 1 μM and with 10–25 mV between 1 and 0.1 μM Ca. The intracellular free Ca concentration was measured to be between 0.1 and 0.7 μM in the neurones. The changes of intracellular Ca in identified voltage-clamped neurones of Aplysia californica were recorded during iontophoretic injections of Ca2+ or EGTA. The decrease of intracellular Ca following EGTA injection was correlated with the suppression of the Ca-dependent K current and with the reduction of Ca-induced inactivation of voltage-dependent Ca current. In identified neurones of the leech Hirudo medicinalis a reversible increase of intracellular Ca2+ was recorded after inhibition of the Na–K pump, either by addition of ouabain (0.5 mM) or by lowering the external K concentration (0.2 mM). This rise in intracellular Ca2+ did not occur, and was even reversed, in the absence of external Na, suggesting the existence of Na–Ca exchange across the leech neuronal membrane.
Extracellular acidification at the surface of depolarized voltage-clamped snail neurones detected with eccentric combination pH microelectrodes
Authors: Thomas R. C.
Published: April 2011

A new design of double micropipette was used to measure intracellular pH, membrane potential, and surface pH of superfused snail neurones. A third double micropipette was used to control the membrane potential via a CsCl-filled barrel and inject HCl iontophoretically. In one series of experiments the surface pH fell by up to one-third of a pH unit when the membrane potential was clamped to 20 mV, pHi was initially 6.7, and extracellular pH was about 7.4 in a medium buffered either with 2 mM HEPES or 2.7% CO2 and 20 mM bicarbonate. In a second series in which surface pH was observed during brief depolarizations to different potentials with different pHi, the potential at which the surface began to acidify varied with pHi with a slope of 32 mV per pH unit. The results confirm that H+ ions leave depolarized snail neurones if the electrochemical gradient is favourable and show that CO2–bicarbonate buffered solutions have a low effective extracellular buffering power for rapid additions of acid.
Swelling and potassium uptake in cultured astrocytes
Authors: Walz Wolfgang
Published: April 2011

The intracellular water content of astrocytes in primary cultures shows a biphasic swelling pattern on exposure to various increased external K+ concentrations over the range of 1.5–100 mM. The two phases (physiological, 1.5–12 mM K+; pathological, 25–100 mM K+) are based on two different mechanisms. Both can be blocked by low Cl− solutions and involve intensive net uptake of K+. However, the physiological phase consists of the activation of a KCl + NaCl carrier, while the Na+ in turn is pumped out by Na+–K+ ATPase, with a resultant net accumulation of KCl. At pathological K+ concentrations the KCl + NaCl carrier is less active because the Na+ driving force, its energy source, is reduced (owing to depolarization by K+). However, the Donnan equilibrium across the cell membrane is heavily disturbed, which leads to passive KCl accumulation. The results suggest that volume changes in cultured glial cells during exposure to high K+ should be taken into consideration since they disguise K+ accumulation when only ion activity is measured.
Retinal spreading depression and the extracellular milieu
Authors: Martins-Ferreira H. , Carmo R. J. do
Published: April 2011

We used isolated chick retina in vitro to study the participation of the extracellular milieu in the occurrence and propagation of spreading depression. The propagation was followed by visual observation or microphotometry and the ionic changes in the extracellular compartment were recorded with double-barreled ion-selective microelectrodes. The front of the spreading wave is accompanied by increased light scattering in the tissue and by decrease of Cl−, Na+, and Ca2+, increase of K+, and an alkaline–acid shift in the extracellular space, concomitant with the slow voltage changes characteristic of the wave. As the spread is related to the chemical steady state of the extracellular milieu, the velocity of propagation is influenced by a balanced interplay of the chemical constituents of the superfusing solution, e.g., K+, [Formula: see text], and glucose facilitate, while Cl− and Mg2+ hinder the wave. Steady-state alterations induced by physical factors (temperature) or related to experimental conditions (speed and direction of superfusate flow) change markedly the velocity of propagation. Generally the procedures that cause increase of velocity augment the susceptibility of the preparation to the reaction and eventually may trigger it. Propagated spreading depression is considered as a chemical diffusion reaction pervading more intensively the inner plexiform layer of the retina.
The effects of endogenous opioids on tension development of isolated, electrically stimulated rat atria
Authors: Wlllerth M. , Thornhill J. A.
Published: April 2011

The possible inotropic effects of all three classes of endogenous opioids were tested alone or in combination with noradrenaline, adrenaline, or carbachol on electrically stimulated atria isolated from male Sprague–Dawley rats. Noradrenaline (6.0 and 12 μM) and adrenaline (4.0 and 8.0 μM) injections caused marked but transient (5 min) dose-related increases in atrial tension compared with preinjection control values, whereas carbachol (0.14 and 1.4 μM) caused a more potent and prolonged (over 15 min) dose-related decrease in atrial tension development. Adrenal enkephalins (0.3–4.0 μM) of methionine enkephalin, leucine enkephalin, Met-enkephalin-Arg6-Phe7, and Met-enkephalin-Arg6-Gly7-Leu8, β-endorphin (0.2–2.0 μM), or dynorphin A(1–13) (0.2–2.0 μM) did not change atrial tension for a 15-min postadministration test period. In addition, these opioids did not affect the positive inotropic effects of noradrenaline (12 μM) or adrenaline (8.0 μM) or the negative inotropic actions of carbachol (1.4 μM) when the same doses of noradrenaline, adrenaline, or carbachol were given alone. These data indicate that endogenous opioids given in micromolar concentrations tested did not affect atrial tension development of electrically stimulated rat atria. Comparing these data with those of past literature, it is suggested that circulating endogenous opioids probably do not have any direct effects on the rat myocardium to affect myocardial contractility.
The central efferent mechanism of brown adipose tissue thermogenesis induced by preoptic cooling
Authors: Imai-Matsumura Kyoko , Nakayama Teruo
Published: April 2011

This study was performed to investigate central efferent mechanisms for brown adipose tissue thermogenesis. In unanesthetized rats, the effects of local anesthesia of the ventromedial hypothalamus, anterior hypothalamus, and lateral hypothalamus were observed on the brown adipose tissue thermogenesis induced by preoptic cooling. Rats had a thermode, thermocouple, and bilateral injection cannulae chronically implanted in the hypothalamus and a thermocouple beneath the interscapular brown adipose tissue. The experiments were done at an ambient temperature of 24–25 °C. Preoptic cooling increased brown adipose tissue and colonic temperatures without shivering. Injecting lidocaine bilaterally into the ventromedial hypothalamus during preoptic cooling reduced brown adipose tissue temperature (Tbat). The mean maximum decrease of Tbat was 0.51 ± 0.26 °C and occurred 5–8 min after lidocaine injection. When lidocaine was injected into the anterior hypothalamus, Tbat increased. The mean maximum increase of Tbat was 0.85 ± 0.29 °C and occurred 4–9 min after lidocaine injection. In the lateral hypothalamus, lidocaine had no effect on Tbat∙Tbat was not influenced by injection of saline into the ventromedial, anterior, or lateral hypothalamus. The efferent pathway from preoptic to brown adipose tissue may thus traverse the medial part of hypothalamus. The ventromedial hypothalamus facilititates and anterior hypothalamus inhibits brown adipose tissue thermogenesis induced by preoptic cooling.
Threshold dissociation of thermoregulatory effector responses in febrile rabbits
Authors: Iriki M. , Hashimoto M. , Saigusa T.
Published: April 2011

When the core temperature stabilizes at a hyperthermic level after iv injection of lipopolysaccharide (LPS), the threshold core temperature for cutaneous vasoconstriction (Thcv) is significantly increased in hot and neutral environments, while the threshold core temperature for shivering (Thsh) is not significantly altered in hot or cold environments but is significantly reduced at thermoneutrality. This type of dissociated threshold alterations of thermoregulatory effector responses seems to be typical for the febrile response of rabbits to LPS. Because the same threshold dissociation can be demonstrated after icv injection of LPS, the systemic and the central effects of LPS in the generation of fever seem to be mediated by identical mechanisms. Prostaglandins of the E series (PGE), one of the mediators considered as important in fever generation, cause parallel increases in Thcv and Thsh when injected icv. This indicates that the mode of action of PGE on the central targets producing hyperthermia differs from that of the ensemble of mediators involved in the generation of LPS fever in rabbits. In rabbits pretreated with aspirin, the threshold dissociation after iv LPS injection still occurs. This indicates that factors other than PGE play an important role in the generation of the threshold dissociation of thermoregulatory effector responses, which is typical for LPS fever. These data indicate also that the states of activity of the thermoregulatory effectors involved in the febrile responses can be altered individually and that the activities of these effectors during LPS fever are quite different from their activities in the control state.
The effect of local heating on blood flow in the finger and the forearm skin
Authors: Nagasaka Tetsuo , Hirata Kozo , Nunomura Tadahiro , Cabanac Michel
Published: April 2011

Blood flow of the finger and the forearm were measured in five male subjects by venous occlusion plethysmography using mercury-in-Silastic strain gauges in either a cool–dry (COOL: 25 °C, 40% relative humidity), a hot–dry (WARM: 35 °C, 40% relative humidity), or a hot–wet (HOT: 35 °C, 80% relative humidity) environment. One hand or forearm was immersed in a water bath, the temperature (Tw) of which was raised every 10 min by steps of 2 °C until it reached 41° or 43 °C. While the other hand or forearm was kept immersed in a water bath (Tw, 35 °C), blood flow in the heated side (BFw) was compared with the corresponding blood flow in the control side (BFc). Under WARM or HOT conditions, linger BFw was significantly lower than finger BFc at a Tw of 39–41 °C in the majority of subjects. When Tw was raised to 43 °C, however, finger BFw became higher than BFc in nearly half of the subjects. In the COOL state, finger BFw did not decrease but increased steadily when Tw increased from 37° to 43 °C. In the forearm, BFw increased steadily with increasing Tw even in WARM–HOT environments. No such heat-induced vasoconstriction was observed in the forearm. From these results we conclude that in hyperthermic subjects, the rise in local temperature to above the core temperature produces vasoconstriction in the fingers, an area where no thermal sweating takes place.
Renal actions of angiotensin II in renovascular hypertension
Authors: Anderson W. P. , Woods R. L. , Denton K. M. , Alcorn D.
Published: April 2011

In renal artery stenosis severe enough to cause hypertension, angiotensin II maintains glomerular filtration rate (GFR) both in the initial high renin phase of hypertension and later when plasma levels are normal. Angiotensin II also maintains GFR in less severe stenosis, which does not cause hypertension. This homeostatic action of angiotensin II to maintain GFR has minimal effects on blood flow. In renal-wrap hypertension, plasma renin levels are elevated for longer than after renal artery stenosis, but in other respects this initial phase of the hypertension is similar to that after renal artery stenosis. GFR is reduced, the rate of development of hypertension is accelerated by angiotensin II, and angiotensin II maintains the glomerular filtration fraction. Renal resistance is markedly increased owing to both compression of the kidney by the hypertrophying renal capsule and to angiotensin II. Thus angiotensin II apparently plays a primarily homeostatic role in renovascular hypertension to maintain glomerular ultrafiltration. It is suggested that the angiotensin II may be formed intrarenally and may act on sites other than resistance blood vessels.