bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonidine fails to reduce pressor responsiveness of conscious spontaneously hypertensive rats to vasopressin
Authors: Datar Sunil , Laverty William H. , McNeill J. Robert
Published: April 2011

Pressor responses and heart rate responses to intravenous injections (3.5–50.0 pmol/kg) of arginine vasopressin (AVP) were recorded in saline- and clonidine-treated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Clonidine (20 μg/kg, i. v.) caused a marked fall of arterial pressure in SHR but not in WKY rats so that, 20 min after the injection of the α2-adrenoceptor agonist, arterial pressure was similar in the two strains of rats. The curve expressing the relationship between the dose of AVP and the increase of arterial pressure for saline-treated SHR was positioned to the left of that for saline-treated WKY rats. This enhanced pressor responsiveness of SHR to AVP may have been related to impaired reflex activity since heart rate fell much less in SHR than in WKY rats for a given elevation in pressure. Pressure responses to AVP were augmented by clonidine in both SHR and WKY rats so that, similar to saline-treated rats, pressor responsiveness to the peptide was still greater in SHR. Heart rate responses to AVP were not altered significantly by clonidine. The results indicate that clonidine fails to enhance reflex activity and reduce pressor responsiveness of SHR to AVP. The increased pressor responsiveness of both SHR and WKY rats to AVP following clonidine was an unexpected finding and may be related to a peripheral interaction between α-adrenergic agonists and AVP.
Nucleus basalis neuronal loss and neuritic plaques in advanced Alzheimer's disease
Authors: Etienne Pierre , Robitaille Yves , Gauthier Serge , Nair N. P. V.
Published: April 2011

All our advanced severe cases of Alzheimer's disease had dramatic cholinergic cell loss in the basal forebrain, even after correction for cell or nucleolus shrinkage. We examined the relation between cell loss in the various subdivisions of the nucleus basalis of Meynert and plaque counts in corresponding and noncorresponding projection areas. This relation was not interpretable because of the ambiguity in the data.
Proprioception during voluntary movement
Authors: Prochazka Arthur
Published: April 2011

In the last decade, a number of laboratories have accumulated data on the firing of single afferent fibres from muscle and skin during movement in awake cats, monkeys and human subjects. While there is general agreement on the firing behaviour of skin afferents and tendon organ (Ib) afferents during movement, there remains a significant divergence of opinion regarding the way in which the response of muscle spindle afferents (Ia and II) to length changes is modified by fusimotor action (e.g., alpha–gamma linkage versus "fusimotor set"). The controversies surrounding the fusimotor system have tended to overshadow the emergence of several important characteristics of propioceptive behaviour, corroborated in separate laboratories, (i) Mean la firing rates during active movements are nearly always higher than at rest. Thus, activation of the fusimotor system is reserved for the control of, or preparation for, movement. In animals, there is now strong evidence that there is usually a tonic component of fusimotor action during rhythmical movements. (ii) During fast, unloaded movements (peak muscle speeds, 0.2 resting lengths/s or more), the firing of both la and II afferents usually increases during lengthening and decreases during shortening. Ib afferents fire during even the most rapid active shortening of their parent muscles, (iii) During powerful shortening contractions performed against significant loads, la firing is often appreciable, suggesting that there is at least some underlying alpha–gamma coactivation. (iv) During fast imposed muscle stretches, la afferents respond with segmented bursts of firing (threshold speed for segmentation, 0.5–1.0 resting length/s). Ib afferents show far less segmentation of discharge under similar circumstances, (v) There are substantial numbers of tendon organ receptors which fire during tasks involving low levels of force.
Effects of noradrenaline, serotonin, and selected antagonists on the vascular smooth muscle of normal and dystrophic chickens
Authors: Howlett S. E. , Triggle C. R. , Hoekman T. B.
Published: April 2011

The pathogenesis of the human muscular dystrophies is unknown, and several competing hypotheses have been proposed. The vascular hypothesis states that muscle fibre necrosis occurs in dystrophy as a result of transient muscle ischemia. Although abnormalities of the vascular system may be demonstrated in dystrophy, their role in pathogenesis remains obscure. The responses to serotonin (5-HT) and noradrenaline (NA) were examined in isolated ischiatic artery preparations from normal and genetically dystrophic chickens. The tension generated in response to 5-HT was greater in arteries from normal chickens than in arteries from dystrophic chickens, whereas responses to NA were similar. Analysis of the concentration–response relationships demonstrated that the dystrophic ischiatic artery was less sensitive to 5-HT than was the normal artery, although the sensitivity to NA was similar in both vessels. The results of this study are not consistent with the view that muscle fibre necrosis in avian dystrophy is a consequence of muscle anoxia. These data do demonstrate pharmacological differences between dystrophic avian arteries and arteries from normal chickens, but their presence may represent merely the expression of dystrophy in vascular smooth muscle.
Effects of tamoxifen citrate and cycloheximide on estradiol induction of rat myometrial gap junctions
Authors: MacKenzie L. W. , Garfield R. E.
Published: April 2011

Longitudinal muscle of myometrial tissues from immature rats were examined by quantitative thin section electron microscopy for the presence of gap junctions after treatment with estradiol with and without tamoxifen, and cycloheximide for 1–6 days. Gap junctions were present between myometrial cells on days 4, 5, and 6 after treatment with estradiol (500 μg/day). Tamoxifen administered concomitantly with estradiol over the 6-day period completely prevented induction of the junctions. Gap junctions were not detected in the myometrium after treatment with tamoxifen alone. Administration of cycloheximide together with estradiol on day 0 of the 6-day period had no effect on gap junction frequency but resulted in a reduction in gap junction size in the myometrium after continued treatment with the hormone. Treatment with cycloheximide on day 1, however, significantly suppressed the effect of further estradiol treatment on the induction of gap junctions in the myometrium. Junctions were not visible in the tissues from animals treated with cycloheximide alone or in the control groups treated with sesame oil. These results indicate that estradiol influences the presence of gap junctions in the myometrium by regulating the synthesis of gap junction proteins through the steroid receptor mechanism.
Sodium manipulation in the management of hypertension. The view against its general use
Authors: Logan Alexander G.
Published: April 2011

Extreme changes in sodium intake do have an effect on blood pressure of both normotensive and hypertensive individuals. Cross-population correlates of average sodium intake and mean population blood pressure are discordant with the results of studies within single populations and cannot be used as sufficient evidence to justify a reduction of dietary sodium intake in the general population to prevent hypertension. Both explanatory and management trials of sodium restriction have yielded contradictory results, and convincing evidence on the nature and size of subgroups of hypertensives with enhanced sodium sensitivity is lacking. The proportion of patients who will follow a moderately restricted sodium diet is low, unless expensive and time-consuming programs of instruction and monitoring are introduced. In light of this evidence, it is premature to recommend diets that are low in sodium as a public health measure and as initial and sole treatment of hypertension.
Is weight loss an effective treatment for hypertension? The evidence against
Authors: Haynes R. Brian
Published: April 2011

Although there are many studies reporting correlations between relative body weight and blood pressure, the correlations are generally of low order. Furthermore, these observational studies provide, at best, circumstantial evidence concerning the effect of weight reduction on elevated blood pressure. After outlining key methodologic criteria for testing the hypothesis that weight loss lowers blood pressure among hypertensive obese subjects, this article reviews the best intervention studies that are available. Despite the demonstration in these randomized trials that weight reduction programs can lower weight successfully, the results for blood pressure lowering are in considerable disagreement. Two studies reported significant lowering of both systolic and diastolic blood pressure, one found significant lowering of systolic pressure only, and two failed to find significant differences in either. The definitive study of substantial weight loss among patients receiving no other antihypertensive treatment or standardized medical treatment with long-term follow-up has yet to be done. At best, weight loss offers very limited benefit for overweight hypertensives. At worst, weight loss programs are expensive to run, cause considerable patient discomfort and may delay the implementation of more effective therapy.
Acute hypokalemic effect of gossypol
Authors: Tam Siu-Cheung
Published: April 2011

Clinical trials had demonstrated that chronic ingestion of gossypol induced infertility in males. Hypokalemia of various severities were reported in volunteers taking gossypol. The purpose of this study is to investigate the effects of acute gossypol infusion into alkalotic rats. Plasma potassium concentration decreased from 4.08 to 2.87 mM after gossypol infusion with minimal change in urinary potassium excretion. The hypokalemic effect of gossypol was also observed in nephretomized rats. Some of the factors that are known to affect potassium distribution between the extracellular and intracellular fluid compartment have been investigated in these rats. Plasma glucose concentration was not significantly altered. Gossypol induced hypokalemia was not blocked in rats treated with propranolol. It is therefore believed that the acute hypokalemic effect of gossypol is a direct shifting of potassium into cells.
Time course of release of atrial natriuretic peptide in the anaesthetized dog
Authors: Ledsome J. R. , Wilson N. , Rankin A. J. , Courneya C. A.
Published: April 2011

In 12 chloralose anaesthetized dogs plasma concentration of immunoreactive atrial natriuretic peptide (IR-ANP) was measured using a radioimmunoassay. Plasma IR-ANP was 74 ± 4.8 pg/mL (mean ± SE) and increased by 39 ± 4.1 pg/mL when left atrial pressure was increased by 10 cm H2O during partial mitral obstruction. Observation of the time course of the changes in IR-ANP during atrial distension showed that IR-ANP was increased within 2 min of atrial distension and declined after atrial distension, with a half-time of 4.5 min. The time course of the changes in IR-ANP was unaffected by vagotomy or administration of atenolol. Maximum electrical stimulation of the right ansa subclavia failed to produce any change in IR-ANP. IR-ANP was higher in coronary sinus plasma than in femoral arterial plasma confirming that the heart was the source of the IR-ANP. The results support the hypothesis that IR-ANP is released from the heart by a direct effect of stretch of the atrial wall rather than by a neural or humoral mechanism involving a reflex from atrial receptors.
The role of insulin in nonshivering thermogenesis
Authors: Shibata Hiroyuki , Pérusse Fleurette , Bukowiecki Ludwik J.
Published: April 2011

The regulation of nonshivering thermogenesis by insulin was studied in cold-acclimated rats (2 weeks at 5 °C) made diabetic after injection with streptozotocin (75 mg/kg, i.p.) and maintained in the warm (25 °C) for 2–7 days. To investigate whether thermogenesis was activated in brown adipose tissue (BAT) of diabetic rats under physiological conditions, conscious rats were briefly exposed to cold (2 h at 5 °C) and the temperature of interscapular BAT (Tbat) was compared with the colonic temperature (Tcol). It was found that Tbat, Tcol, and Tbat – Tcot (an index of thermogenesis activation in BAT) were significantly reduced in 7-day diabetic rats (P < 0.01) but not in 2-day diabetic animals, suggesting that diabetes progressively decreases BAT thermogenic capacity. To further assess whether the maximal capacity of BAT for nonshivering themiogenesis was affected by the lack of insulin, the calorigenic response to noradrenaline (0.4 mg/kg, i.m.) was determined at 25 °C in anesthetized animals using an open circuit respirometer. The results showed that the calorigenic response to noradrenaline was inhibited by 50 and 70% in 2- and 7-day diabetic rats, respectively. Significantly, tissue weight, protein content, and cytochrome oxidase activity of interscapular BAT were also decreased by 30–40% and 50–70% in the same animals. Insulin treatment of 3-day diabetic rats for 4 days (6.5 U/day per rat) restored their calorigenic response to noradrenaline to control levels. However, this parameter was not altered by an acute injection of insulin (0.5 U/kg). It is concluded that the maximal capacity of BAT for thermogenesis is rapidly inhibited by diabetes. Insulin is not directly involved in the activation of BAT thermogenesis but is essential for the maintenance of a high capacity for nonshivering thermogenesis. Insulin may regulate BAT respiratory capacity by playing a permissive role in the control of mitochondrial protein synthesis.
Effects of dietary cod liver oil on fatty-acid composition and calcium transport in isolated adult rat ventricular myocytes and on the response of isolated hearts to ischemia and reperfusion
Authors: Karmazyn Morris , Horackova Magda , Murphy Mary G.
Published: April 2011

Three-week-old male and female rats were placed either on standard rat chow or chow supplemented with 10% cod liver oil for 12 weeks. Animals fed cod liver oil demonstrated reduced body weights. Cod liver oil feeding produced a significant reduction in the ratio of (n−6)/(n−3) fatty acids in phospholipids of the isolated myocytes. The primary changes included a significant decrease in archidonic acid (20:4, n−6) and elevations in eicosapentaenoic acid (20:5, n−3) and docosahexaenoic acid (22:6, n−3). Furthermore, isolated myocytes from cod liver oil fed rats exhibited an enhanced 45Ca2+ uptake, although 45Ca2+ release was unaffected. Dietary cod liver oil had little effect on cardiac response to ischemia and reperfusion. Thus, neither developed force or resting tension was significantly affected by diet, although the latter tended to be elevated in hearts from cod liver oil fed animals. Release of creatine kinase was unaltered by diet. The release of 6-ketoprostaglandin F1α from isolated hearts was significantly reduced by dietary cod liver oil, likely due to the reduced levels of arachidonic acid. Our study indicates that dietary cod liver oil and subsequent changes in phospholipid fatty-acid content are accompanied by changes in Ca2+ transport in isolated cardiac myocytes. However, this diet produces little effect on the cardiac response to acute ischemia and reperfusion.
Posttetanic potentiation and skeletal muscle fatigue: interactions with caffeine
Authors: MacIntosh Brian R. , Gardiner Philip F.
Published: April 2011

The purpose of this study was to determine the interaction of three factors that modify twitch contraction amplitude in the rat gastrocnemius muscle in situ: posttetanic potentiation, fatigue, and caffeine. Posttetanic (200 Hz for 1 s) twitch responses were observed before and after 15 Hz stimulation for 6 min (group FS), injection of caffeine (75 mg/kg dissolved in saline, gropu NC), a combination of both repetitive stimulation and caffeine injection (group FC), or no treatment (group NS). Developed tension increased significantly with posttetanic potentiation and caffeine injection and these potentiating factors were additive (group NC). Repetitive stimulation attenuated the twitch response and the fatigued muscle was still responsive to the potentiating factors. Posttetanic potentiation was accomplished primarily by a significant increase in the peak rate of force development whereas caffeine potentiation and fatigue were effected with a proportional change in contraction time. It seems likely that the mechanism of posttetanic potentiation is not the same as the mechanism of caffeine-induced potentiation. Caffeine-induced potentiation is known to be related to increased release of calcium. Because changes in contraction time with fatigue were opposite to those associated with caffeine potentiation, it is proposed that the attenuated twitch response in fatigue results from reduced release of calcium.
Diazepam reveals different rate-limiting processes in rat skeletal muscle contraction
Authors: Chua Michael , Dulhunty Angela F.
Published: April 2011

The action of the tranquilizer diazepam on rat skeletal muscle showed that relaxation of isometric twitches is controlled by different processes in extensor digitorum longus (fast-twitch) and soleus (slow-twitch) muscles. Diazepam caused an increase in the amplitude of twitches in fibres from both muscles but increased the twitch duration only in soleus. The amplitude of fused tetani were reduced in both muscles and the rate of relaxation after the tetanus slowed by as much as 34% when the amplitude of the tetanus was reduced by only 11%. The slower tetanic relaxation indicated that calcium uptake by the sarcoplasmic reticulum was slower than normal in slow- and fast-twitch fibres. We conclude therefore that calcium uptake by the sarcoplasmic reticulum is rate limiting for twitch relaxation in slow-twitch but not fast-twitch fibres and suggest that calcium binding to parvalbumin controls relaxation in the fast fibres.
Long-term isoprenaline administration produces an increase in capillarity in the soleus muscle of the rat
Authors: Sillau A. H. , Philippi Maria De Lourdes
Published: April 2011

The effects of isoprenaline administration (300 μg/kg for 5 weeks) on rat soleus muscle capillarity and glycolytic and oxidative capacities were evaluated. The treatment resulted in ventricular hypertrophy. The activities of lactic dehydrogenase, pyruvate kinase, citrate synthase, and cytochrome c oxidase in soleus muscle homogenates were not different between control and isoprenaline-injected animals. Capillaries were visualized in muscle cross sections treated to demonstrate ATPase activity after acid preincubation. Capillary density was higher in the experimental (873 ± 38 capillaries/mm2) than in the control (713 ± 33 capillaries/mm2) animals. Capillary to fiber ratio was also higher in the experimental (2.47 ± 0.10) than in control (2.09 ± 0.08) animals, but fiber cross-sectional area was not changed by the treatment (2836 ± 87 μm2 in controls and 2951 ± 136 μm2 in experimental). A plot of capillary to fiber ratio vs. fiber cross-sectional area showed that at a given fiber cross-sectional area the value of capillary to fiber ratio of the treated animals was higher than that of the controls. This indicates that treatment resulted in the proliferation of microvessels. The results suggest that prolonged β-adrenergic stimulation results in the development of new capillaries but that this is not accompanied by increases in the oxidative capacity of the soleus muscle of the rat.
Competition between fatty acids and carbohydrate or ketone bodies as metabolic fuels for the isolated perfused heart
Authors: Forsey Robert G. P. , Reid Kathy , Brosnan John T.
Published: April 2011

The ability of carbohydrate fuels (lactate, pyruvate, glucose) and the ketone bodies (acetoacetate, β-hydroxybutyrate) to compete with fatty acids as fuels of respiration in the isolated Langendorf-perfused heart was studied. Oleate and octanoate were used as fatty acid fuels since oleate requires carnitine for entry into mitochondria, whereas octanoate does not. The two ketone bodies inhibited the oxidation of both oleate and octanoate implying an intramitochondrial site of action. Pyruvate, lactate, and lactate plus glucose inhibited oleate oxidation but not octanoate oxidation, indicating a mechanism of inhibition that involves the carnitine system. Pyruvate was a more potent inhibitor than lactate at equal concentrations, but the effect of lactate could be greatly increased by dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase. The physiological and mechanistic implications of these observations are discussed.
Effect of rifampin, phenobarbital pretreatment, and acetyiator phenotype on acetylisoniazid metabolism in the rabbit
Authors: Thomas Barry H. , Zeitz W. , Whitehouse L. W.
Published: April 2011

The metabolism of [14C]acetylisoniazid was studied in male New Zealand White rabbits. Pretreatment of the rabbits with the microsomal enzyme inducers rifampin and phenobarbital had little effect on acetylisoniazid metabolism. Rifampin appears to produce some inhibition of acetylation of the metabolite acetylhydrazine to diacetylhydrazine. Acetylation phenotype was an important factor. Covalent binding of 14C to hepatic protein increased as the acetylation rate decreased. In plasma and urine acetylhydrazine levels were negatively correlated with acetylation rate and diacetylhydrazine levels were positively correlated as one would expect. It was concluded that in the rabbit covalent binding to hepatic protein was more dependent on the acetylation rate than on induction of microsomal oxidase.
Airway epithelium and bronchial reactivity
Authors: Vanhoutte P. M.
Published: April 2011

Damage to or dysfunction of respiratory epithelial cells may contribute to the etiology of bronchial hyperreactivity in asthma and airway infection. In the vascular system, endogenous neurohumoral mediators can cause either relaxation or contraction of the smooth muscle of the blood vessel wall because they cause the release of relaxing or contracting factor(s), respectively, from the vascular endothelial cells. This brief overview summarizes data from the author's laboratory, which suggests that release of relaxing factor(s) from epithelial cells contributes to the regulation of bronchomotor tone.
The role of histamine and other mediators in microvascular changes in acute inflammation
Authors: Movat Henry Z.
Published: April 2011

In addition to bronchial smooth muscle, histamine and other mediators act in bronchial asthma on the microcirculation of pulmonary connective tissue. The mediators induce enhanced blood flow, and by acting on the blood–tissue barrier, they induce increase in vasopermeability with edema and in more severe injury microhemorrhage and microthrombosis and infiltration of the connective tissue by leukocytes, predominantely neutrophils. The scheme proposed 10 years ago by K. F. Austen and co-workers in 1976 still holds true: a short-acting humoral–cellular phase is followed by a longer-acting pathopharmacologic or inflammatory phase. Some mediators, including histamine, serotonin, bradykinin, the sulfido leukotrienes and platelet activating factor, have a direct effect on endothelium and smooth muscle cells and more severe injury is due to mediators that exert their effect via neutrophils, which release lysosomal constituents. The intact complement-derived fragments C3a and C5a act directly and for a short period, as do histamine and the other direct-action mediators. The accumulation of neutrophils is brought about by C5a and its stable derivative C5ades Arg, leukotriene B4, PAF, and interlcukin-1. Unlike the direct-action mediators, whose effect on the microcirculation does not extend beyond 20–25 min, those mediating via neutrophils have a delayed effect (peak 1–2 h), which parallels the neutrophil influx. The direct action mediators exert their effects on the microcirculation also in neutropenic animals. The most potent agents causing enhanced blood flow are the prostaglandins of the E class. Through the enhanced blood flow increase in vasopermeability, neutrophil emigration and hemorrhage are enhanced. Concerning mechanisms, histamine and other direct-action mediators induce subtle changes, characterized by interendothelial gaps in postcapillary venules and no visible endothelial injury. Neutrophil lysosomes, in concert with oxygen radicals, cause a degradation of subendothelial and perivascular matrices, including basement membranes and fragmentation of endothelium. The entire microcirculation is effected, but primarily the postcapillary venules. The described changes markedly influence the changes taking place in the airways.
Plant phenolics as inhibitors of mutational and precarcinogenic events
Authors: Newmark H. L.
Published: April 2011

Initiation of chemical carcinogenesis involves the intracellular formation of a highly reactive electrophile that can attack many chemical nucleophiles in the cell, including DNA, a process that seems to be a central mechanism of initiation. Competing chemical nucleophiles in the cell, such as endogenous glutathione, can act as protecting or blocking agents against the attack on DNA. There are chemical substances in our food supply that may act as anticarcinogens or antimutagens by blocking or trapping ultimate carcinogen electrophiles in a nucleophilic chemical reaction, to form innocuous products. A continuous input of these substances could serve as an additional buffer against DNA damage, supplementing the endogenous systems qualitatively and quantitatively. Certain plant phenolics can be effective inhibitors of chemical mutagens and (or) carcinogens. Tetrapyrroles and porphyrins, both plant and animal, can also act as blocking agents. Both plant phenolics and porphyrins are primarily active against aromatic carcinogens as inhibitors of mutagenesis in in vitro systems. Plant phenolics have also demonstrated inhibiting activity against aromatic chemically induced carcinogenesis.
Modulation of calcium by the carcinogenic process in the liver induced by a choline-deficient diet
Authors: Ghoshal Amiya K. , Laconi Ezio , Willemsen Frederick , Ghoshal Amit , Rushmore Thomas H. , Farber Emmanuel
Published: April 2011

A diet devoid of choline and low in methionine (CD), without any added carcinogen, has been shown to induce 100% preneoplastic nodules and more than 50% cancer in the rat liver. Attempts to understand the mechanism by which a CD diet induces liver cell cancer revealed that like chemical carcinogens, a CD diet also appears to cause alterations in DNA, perhaps mediated by free radicals. Indeed, a CD diet induces nuclear lipid peroxidation prior to the changes in DNA. The CD diet induced DNA alterations coupled with continuing liver cell proliferation may account for the induction of initiated hepatocytes by the CD diet. To gain insight into the nature of free radicals generated by the CD diet, experiments were designed to determine whether agents that modulate free radical effects influence the CD diet induced changes in the liver. We investigated the effect of Ca2+ in the modulation of CD diet induced alterations in the liver. The results show that extra Ca2+ when added to the CD diet prevented some of the early changes due to choline deficiency, such as nuclear lipid peroxidation and DNA damage, but had little or no effect on the triglyceride accumulation in the liver. Also, the same CD diet with extra Ca2+, when used as a promoter after initiation by diethylnitrosamine, decreased the number and size of early putative preneoplastic foci and nodules.
Effects of autonomic stimulation on plasma immunoreactive atrial natriuretic peptide in the anesthetized rabbit
Authors: Rankin A. J. , Wilson N. , Ledsome J. R.
Published: April 2011

Infusions of norepinephrine led to a significant sevenfold increase in plasma immunoreactive atrial natriuretic peptide, while infusions of acetylcholine caused no significant change in the level of the peptide. Efferent stimulation of the right vagus nerve or right inferior cervical ganglion in anesthetized, vagotomized rabbits produced no significant changes in the immunoreactive atrial natriuretic peptide. The findings suggest that the mechanism by which norepinephrine releases immunoreactive atrial natriuretic peptide is not the result of a direct action on the cardiac myocytes.
The actions of diazepam and diphenylhydantoin on fast and slow Ca2+ uptake processes in guinea pig cerebral cortex synaptosomes
Authors: Rampe D. , Ferrante J. , Triggle D. J.
Published: April 2011

The activities of diazepam and diphenylhydantoin as inhibitors of the fast and slow phases of 45Ca2+ uptake in response to K+ depolarization and of [3H]nitrendipine binding were examined in guinea pig cerebral cortex synaptosomes. The slow phase of 45Ca2+ uptake was abolished in Na+-free media (choline substitution) and was more sensitive to inhibition by 3,4-dichlorobenzamil and represents a Na+-dependent Ca2+ uptake process. The fast component of uptake represents activation of voltage-dependent Ca2+ channels. Diazepam (to 300 μM) was selectively active against the fast component of 45Ca2+ uptake. The benzodiazepines Ro 11-3624 and Ro 11-3128 were similarly selective with a modest stereoselectivity against the fast component of 45Ca2+ uptake. Diphenylhydantoin (100 and 200 μM) blocked nonselectively both fast and slow phases of Ca2+ uptake. Diazepam (60 μM) and diphenylhydantoin (200 μM) blocked [3H]nitrendipine binding in a competitive manner. Diazepam and diphenylhydantoin probably exert at least part of their anticonvulsant activity by inhibition of voltage-dependent Ca2+ channels.
Prevention of hypertension and maintenance of normotension in spontaneously hypertensive rats is dependent on continuous severe dietary sodium restriction
Authors: Wilczynski Esther A. , Leenen Frans H. H.
Published: April 2011

Spontaneously hypertensive rats were placed on a very low (9 μmol/g) or control (101 μmol/g) sodium diet at birth or 4 weeks of age. These diets were continued to 16 weeks of age, or at 10 weeks were increased from 9 to 26 or 101 μmol/g. Sodium restriction initiated up to 4 weeks of age and continued to 16 weeks of age severely retarded growth, prevented the development of hypertension, and reduced effective sympathetic activity as assessed by the response of blood pressure to ganglionic blockade. Only a small increase in sodium intake at 10 weeks of age (to 26 μmol/g or more) resulted in a marked increase in growth rate, an elevation of blood pressure, and a return of the response to ganglionic blockade towards normal. These data indicate that very severe sodium restriction must be continuous to maintain decreased sympathetic activity and normal blood pressure in spontaneously hypertensive rats. It appears that severe dietary sodium restriction suppresses one or more of the mechanisms involved in normal growth and development of hypertension in spontaneously hypertensive rats, but these mechanisms may still proceed once the sodium intake is increased.
The mechanism of ryanodine action in rabbit ventricular muscle evaluated with Ca-selective microelectrodes and rapid cooling contractures
Authors: Bers Donald M. , Bridge John H. B. , MacLeod Kenneth T.
Published: April 2011

Cellular Ca uptake and efflux in rabbit ventricular muscle was measured using double-barreled Ca microelectrodes in the extracellular space. When repetitive stimulation was stopped there was a slow loss of cellular Ca. Upon resumption of stimulation Ca was taken up by the cells. These Ca movements are thought to represent the loss of Ca from the sarcoplasmic reticulum and the cell during rest and the refilling of the sarcoplasmic reticulum during stimulation. Ryanodine (100 nM) greatly enhanced both the efflux of Ca during rest and the uptake of Ca induced by stimulation. These results are consistent with the conclusions drawn below, but they are dependent upon the interpretation that these extracellular Ca depletions are indicative of sarcoplasmic reticulum Ca movements. To examine further this process, contractures induced by rapid cooling to 0 °C were used as an independent assay of sarcoplasmic reticulum Ca content. These rapid cooling contractures were smaller after longer rest intervals (declining with a half time of 1.5 min). In the presence of ryanodine, the rapid cooling contracture immediately after a contraction was greater than that seen under control conditions. However, in the presence of ryanodine these rapid cooling contractures decline as a function of rest duration with a half time of about 1 s. These results suggest that in the presence of ryanodine the sarcoplasmic reticulum can still take up Ca, but that it also loses this Ca very rapidly at the onset of rest. Caffeine (20 mM) inhibits both the extracellular Ca depletions and the rapid cooling contractures that are attributed to the sarcoplasmic reticulum Ca content changes (in the presence or absence of ryanodine). These results suggest the following two actions of ryanodine: (i) inhibition of sarcoplasmic reticulum Ca release into the cytoplasm upon activation, and (ii) enhancement of Ca loss from the sarcoplasmic reticulum upon the termination of stimulation and extrusion from the cell without activation of appreciable tension.
Glial potentials in hippocampus
Authors: Casullo J. , Krnjević K.
Published: April 2011

In rats under urethane anaesthesia, intracellular recordings were made from 36 cells, mainly in CA1, that had all the characteristics of glia: unusually high and stable resting potentials (−79.6 ± 6.0 mV, mean ± SD) and total absence of spikes or synaptic potentials. They were exceptionally sensitive to surrounding neuronal activity, being readily depolarized by very low frequency stimulation (0.5-2 Hz) of the fimbria. In the range 0.5–2 Hz, the mean peak depolarizations increased linearly with frequency of fimbrial stimulation (9.1 ± 0.53 mV/Hz). At frequencies of 5 Hz or more, the depolrizations were highly variable, sometimes reaching a maximum of 25–30 mV, but the overall mean was not significantly greater than for 2 Hz stimulation. The depolarizations decayed slowly, with a half-time of 4.2 ± 1.22 s and were often followed by a prolonged undershoot (lasting over 1 min). Alvear and especially septal stimulation were much less effective in evoking glial depolarizations. One cell that initially had all the characteristics of a glia, during very prolonged stable recording, developed responses, such as synaptic potentials and 20–40 mV action potentials evoked by fimbrial or alvear stimulation, consistent with strong electrical coupling to at least one neighbouring neuron.
Potassium loss from hypoxic myocardium: influence of external K concentration
Authors: Leblanc Normand , Ruiz-Ceretti Elena , Chartier Denis
Published: April 2011

The influence of external potassium Ko and tetraethylammonium on the cellular K content of hypoxic myocardium was investigated. Perfused rabbit hearts were submitted to 60 min hypoxia in medium containing 5 mM K throughout or either low (1.5 mM) or high (10 mM) K during the last 20 min of hypoxia. Paced electrical activity (2.5 Hz) was kept throughout the experiments. Tissue samples excised from the left ventricle were analyzed for total water, inulin space, and Na and K content. Lowering Ko to 1.5 mM increased both K loss and Na accumulation. Addition of 3.5 mM RbCl under these conditions reversed Na accumulation to levels found for hypoxia in normal medium but did not modify the cellular K loss. Tetraethylammonium (10 mM) did not alter Na accumulation but partly prevented the decrease in K content produced by hypoxia. A similar effect was observed by increasing Ko to 10 mM. At this high Ko prolongation of hypoxia did not enhance K loss. Abolition of electrical activity by TTX in a high K solution prevented K loss and reduced the sodium content. These results are consistent with the view that voltage-dependent channels are implicated in the K loss induced by hypoxia or ischemia. Furthermore, they indicate that the K loss may be modulated by external K because of the influence of the electrochemical gradient on passive K efflux and thus provide an explanation for the existence of a plateau in the early extracellular K accumulation observed during cardiac ischemia.
Cationic membrane conductances induced by intracellularly elevated cAMP and Ca2+: measurements with ion-selective microelectrodes
Authors: Swandulla D.
Published: April 2011

Adenosine 3′,5′-cyclic monophosphate (cAMP) and CaCl2 were injected by a fast and quantitative pressure injection technique into voltage-clamped, identified Helix neurons. Intracellular elevation of cAMP as well as of Ca2+ activated an inward current (IcAMP and IN). To identify the ionic fluxes during IcAMP and IN changes in [Na+]i, [K+]o, [H+]i, and [Cl−]i were measured with ion-selective microelectrodes (ISMs). Near resting potential, Na+ was the main carrier of IcAMP. K+, and less effectively Ca2+, could substitute for Na+ in carrying IcAMp. H+ and Cl− were excluded as current carriers for IcAMP by means of ISMs. Simultaneous to this action, cAMP decreased a K+ conductance. This decrease was associated with a reduction of the K+ efflux activated by long-lasting depolarizing voltage steps, as directly measured with ISMs located near the external membrane surface. The nearly compensatory increase and decrease of two membrane conductances in the same neuron left the cell input resistance unchanged despite the considerable depolarizing action of intracellularly elevated cAMP. IN was also of nonspecific nature. However, our findings indicate less selectivity for the Ca2+-activated nonspecific channels. Large cations such as choline, TEA, and Tris passed nearly as well as Na+ through the channels. Measurements with ISMs showed that [H+]i and [Cl−]i were unchanged during IN. IN was largest in bursting pacemaker neurons compared with other cells of similar size. It was found to be essential for the burst production in these cells. IcAMP, on the other hand, might be involved in the presynaptic facilitatory action of cAMP, which as yet was attributed solely to a reduction of a K+ conductance.
Regulation of intracellular pH in sheep cardiac Purkinje fibre: interactions among Na+, H+ and Ca2+
Authors: Kaila K. , Vaughan-Jones R. D. , Bountra C.
Published: April 2011

Experiments were performed on sheep cardiac Purkinje fibres using pH- and sodium-selective microelectrodes, while simultaneously measuring tension, to determine if the fall in intracellular pH (pHi) following a rise in intracellular Na+ activity [Formula: see text] is caused by inhibition or reversal of acid extrusion on Na+–H+ exhange. A rise in [Formula: see text] was induced either by using the cardioactive steroid strophanthidin to inhibit the sarcolemmal Na+–K+ pump or by increasing the frequency of stimulation (0–4 Hz). Both of these manoeuvres led to an increase in [Formula: see text] and a decrease in pHi. Following exposure to strophanthidin, amiloride (an inhibitor of sarcolemmal Na+–H+ exchange) produced a decrease in both pHi and [Formula: see text]. These effects of amiloride increased with decreasing pHi, indicating that acid extrusion on Na+–H+ exchange is stimulated by the fall in pHi. The changes in intracellular Na+ and H+ caused by amiloride were quantitatively consistent with an electroneutral stoichiometry. The fall in pHi during strophanthidin exposure is therefore not caused by inhibition or reversal of acid extrusion Na+–H+ exchange. It is likely that the fall in pHi during a rate increase is also independent of Na+–H+ exchange. This is because (i) it has been shown previously to occur in the presence of amiloride and (ii) the calcium antagonist D600 completely abolished the stimulation-dependent fall in pHi. It is concluded that the intracellular acidosis following inhibition of the sarcolemmal Na+–K+ pump or following an increase in the rate of stimulation is secondary to a rise in intracellular calcium.
Single voltage-dependent K+ and Cl− channels in cultured rat astrocytes
Authors: Sonnhof U.
Published: April 2011

The kinetic reactions of a voltage-dependent K+ channel, which constituted about 14% of all the recorded K+ channels in the membrane of cultured rat astrocytes were studied in detail. A scheme of one open and three closed states is necessary to describe the kinetic reactions of this channel. The channel contributes little to the resting membrane potential. Its steady state open probability (Po) is 0.06 at −70 mV. When the cell is depolarized to 0 mV, Po approaches 1. This represents a 17-fold increase. Such channels could contribute to the potassium clearance by enhancing the effect of "spatial buffering." Additionally, single anion-selective channels with very high conductances were found in inside-out patches in approximately 15% of all recorded channels in the membrane of rat astrocytes. Channel openings are characterized by more than one conductance level; the main level showed a mean conductance of 400 pS. These channels are divided into two groups. Approximately 90% of the recorded chloride channels showed a strong voltage dependency of their current fluctuations. Within a relatively small potential range (±15 mV) the channels have a high probability of being in the active state. After a voltage jump to varying testing potentials in the range of ±20 to ±50 mV the channels continued to be in the active state for some time and then closed to a shut state. If the testing potential persisted, the channels were not able to leave this shut state. The active state could only be reached again if the membrane potential was reset close to zero for some time. The time course of the current relaxation was measured by ensemble averaging of single channel current fluctuations. When at the end of a testing potential the voltage was set back to zero, the channel remained in the shut state for some time before it reached the open state again. The voltage dependence of this recovery period was analyzed as well but is not shown in this paper. The reaction indicates a nonstationary process as the open probability is time dependent, and for better differentiation I will call these channels nonstationary chloride channels. A subgroup of 10% of all recorded chloride channels showed no voltage-dependent kinetic reactions. I will denote them as stationary chloride channels. Both types of Cl− channels are mainly permeable to anions but showed a slight permeability to cations. An idea of the role of these channels at this state must be highly speculative. The possibilities include a cell to cell transfer of material or a regulation of the internal or external ion environment. In the latter case, they could provide an uptake mechanism for potassium ions in addition to the spatial buffer currents.
Hemolytic uremic syndrome in renal allografted patients treated with cyclosporin
Authors: Giroux Lise , Smeesters Christian , Corman Jacques , Paquin François , Allaire Guy , St-Louis Gilles , Daloze Pierre
Published: April 2011

The classical triad of hemolytic uremic syndrome (microangiopathic hemolytic anemia, severe thrombopenia, and renal failure) developed de novo in three of our renal transplanted patients under cyclosporin A treatment. The predominant morphologic findings in the grafts consisted of glomerular and arteriolar thrombosis as well as arteriolonecrosis, all features of the syndrome. In one instance, ischemic bowel disease supervened after graft removal and was associated with persistent low grade microangiopathic process. De novo hemolytic uremic syndrome has been reported in patients treated with cyclosporin A following bone marrow or liver transplantation as well as in a few renal graft recipients. This peculiar form of cyclosporin A nephrotoxicity should not be confused with acute rejection of the renal transplant.
Similar poststimulatory pressor responses with different mechanisms in response to excitation of the locus coeruleus before and after acute adrenalectomy
Authors: Drolet Guy , Gauthier Pierre
Published: April 2011

Electrical stimulation of the locus coeruleus in anesthetized rats evoked a biphasic pressor response consisting of an initial sharp rise in blood pressure at the onset of stimulation, followed by a second elevation after cessation of the stimulus. This response, which was accompanied by an increase in plasma noradrenaline and adrenaline levels, was stable and could be easily reproduced over time. Sympathectomy by administration of guanethidine selectively abolished the primary pressor response. β-Adrenergic blockade by intravenous administration of sotalol enhanced the secondary pressor response without affecting the primary component. Adrenal demedullation performed 24–48 h before the experiments selectively prevented the secondary pressor component. In contrast, acute adrenalectomy carried out during the experiment to impair the adrenomedullary secretions eliminated the secondary pressor response to stimulation of the locus coeruleus only in sympathectomized or in sotalol-treated rats but not in intact rats in which the response persisted. The latter, however, could be abolished by the administration of either guanethidine or sotalol, and it disappeared following repeated stimulation of the locus coeruleus. The study demonstrates that similar poststimulatory pressor responses with different underlying mechanisms can be elicited on excitation of the locus coeruleus before and after acute adrenalectomy in the rat. The results also suggest that intraneuronal adrenaline may be involved in the response evoked in acutely adrenalectomized animals.
Phosphate transport and alkaline phosphatase in confluent MDCK cell monolayers
Authors: Letellier Marc , Brière Normand , Plante Gérard E. , Petitclerc Claude
Published: April 2011

Several studies have suggested that the brush border membrane alkaline phosphatase is involved in the renal reabsorption of inorganic phosphate along the proximal convoluted tubule. However, other studies on the influence of l(−)bromotetramisole, an inhibitor of alkaline phosphatase, upon phosphate transport into brush border membrane vesicles have failed to show an involvement of alkaline phosphatase. The present experiments were designed to demonstrate that the MDCK (Madin, Darby, canine, kidney) cell line can be used as an alternative model to study phosphate transport, to examine the effect of l(−)bromotetramisole and the role of alkaline phosphatase. MDCK cell monolayers were concomitantly used for alkaline phosphatase activity measurement and phosphate transport analysis. While alkaline phosphatase activity increases by 37-fold from day 2 to day 8 of culture, reaching a plateau at day 10, the sodium-dependent phosphate transport into the cell monolayers decreases by 2-fold during that same period. The phosphate transport was also studied in the presence of l(−)bromotetramisole at pH 8.5. The sodium-dependent phosphate uptake of inorganic phosphate is reduced by 43% in the presence of l(−)bromotetramisole at day 3 of culture but is not reduced in the 7-day-old culture. Our results suggest a participation of alkaline phosphatase upon phosphate transport in MDCK cell monolayers and indicate that this cell line constitutes a good model to study the relationship between alkaline phosphatase and phosphate transport.