bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistence of central respiratory rhythmogenesis after maximal acetylcholinesterase inhibition in unanaesthetized cats
Authors: Foutz Arthur S. , Delamanche Iroudayanadin S. , Denavit-Saubié Monique
Published: April 2011

Cats were given systemically the anticholinesterase paraoxon at a dosage (3 mg/kg i.v.) that produced a maximal (over 90%) inhibition of brainstem acetylcholinesterase. All paralyzed and artificially ventilated animals were either unanaesthetized (decerebrated or ventilated with 70% nitrous oxide and 30% oxygen) or anaesthetized (with pentobarbital, α-chloralose, or halothane). In unanaesthetized cats, paraoxon produced an immediate rise in arterial blood pressure and did not suppress phrenic nerve respiratory discharges, while in anaesthetized animals it produced an immediate and long-lasting hypotension and a complete arrest of central respiratory activity. It is concluded that acetylcholine accumulation may not suppress respiratory rhythmogenesis and that most anaesthetics may considerably alter the response of cardiorespiratory cholinergic mechanisms to anticholinesterase administration.Key words: respiratory rhythmogenesis, acetylcholinesterase, cholinergic mechanisms, anaesthesia, cat.
Synaptic restructuring during long-term facilitation at the crayfish neuromuscular junction
Authors: Wojtowicz J. M. , Marin L. , Atwood H. L.
Published: April 2011

Long-term facilitation was induced by 20-Hz stimulation of the motor axon innervating the opener muscle of the crayfish, Procambarus clarkii. Excitatory postsynaptic potentials remained potentiated for several hours after stimulation. Structural correlates of potentiation were sought. Nerve terminals of the motor axon were fixed for electron microscopy in unstimulated preparations (controls), and during and after 20-Hz stimulation. Synapses were reconstructed from micrographs obtained from serial sections. Synaptic contact area and the number of vesicles at the presynaptic membrane did not change after 20-Hz stimulation, but the latter decreased during stimulation. Presynaptic dense bars ("active zones") decreased in number during and increased after stimulation, while perforated synapses increased after stimulation. Modification of presynaptic structures occurs rapidly and may be linked to long-lasting changes in quantal content of transmission.Key words: facilitation, plasticity, release site, synaptic vesicle, transmitter release.
Effect of V-9-M, a peptide fragment derived from procholecystokinin, on memory processes in the rat
Authors: Takashima Akira , Itoh Shinji
Published: April 2011

It has been reported that a nonapeptide (Val-Pro-Val-Glu-Ala-Val-Asp-Pro-Met) called V-9-M is produced from procholecystokinin in the brain. Since this peptide is particularly abundant in the hippocampus, septum, and amygdala, V-9-M may be involved in memory processes. The present study was attempted to observe the effect of V-9-M on memory processes of rat performing a one-trial passive avoidance task and a platform jumping active avoidance task. The results indicate that injection of V-9-M into the lateral ventricle of the rat prevents experimental amnesia induced by electroconvulsive shock in passive avoidance testing, and that this effect is not significantly affected by cholecystokinin-8 antagonists. V-9-M also causes a long-lasting enhancement of memory in the active avoidance task. These results suggest that V-9-M may participate in the facilitation of memory.Key words: V-9-M, passive avoidance response, active avoidance response, proglumide, L-364,718, memory.
Lack of cardiac α1-adrenoceptor involvement in ethanol-induced cardiac hypertrophy
Authors: Adams Michael A. , Hirst Maurice
Published: April 2011

The development of cardiac hypertrophy was examined in rats given ethanol in a nutritionally adequate, liquid diet mixture, by intubation, in severely intoxicating doses at 8-h intervals for up to 96 h, alone or in combination with prazosin. Other groups of rats received isocalorically paired quantities of maltose–dextrin. Adrenal glands of rats receiving ethanol were larger than those from control animals. Prazosin did not affect this measure. In contrast, concurrent treatment with prazosin enhanced the loss of medullary catecholamines and noradrenaline from hearts of rats given ethanol, while it had no such effects in controls. Reflecting these changes, excreted quantities of catecholamines were markedly increased in rats given ethanol and prazosin. Hearts of animals given the combined treatment of ethanol and prazosin showed cardiomegaly at 24 h, when there was an increase of about 20% in proportional heart weight, an increase that persisted through the remaining 3 days of the study. At 48 h, hearts of animals given prazosin and ethanol were heavier than those given ethanol alone. A significant correlation between catecholamine excretion and the development of cardiac hypertrophy was identified. The results of the study show that prazosin can enhance effects of ethanol on the peripheral sympathetic nervous system. Moreover, the results suggest that postsynaptic α1-adrenoceptor stimulation in the heart is not an important contributor to ethanol-induced cardiomegaly.Key words: cardiac hypertrophy, ethanol, catecholamines, α1 adrenoceptor, prazosin.
Differential biotransformation of the enantiomers of isoidide dinitrate in isolated rat aorta
Authors: Stewart David H. , Hayward L. Douglas , Bennett Brian M.
Published: April 2011

Previous studies have demonstrated that the D-enantiomer of isoidide dinitrate (IIDN) is 10-fold more potent than the L-enantiomer for relaxation and cyclic GMP accumulation in isolated rat aorta. To test whether preferential biotransformation of D-IIDN to a species that activates guanylate cyclase is the basis for this observed enantioselectivity, paired segments of rat aorta were exposed to D- and L-IIDN and the tissue accumulation of the parent compound and the formation of their respective metabolites (D- and L-isoidide mononitrate, IIMN) were determined. The extent of relaxation of rat aorta following exposure to 2 μM D-IIDN was greater than that by L-IIDN over a 5-minute time course, and this was associated with a higher rate of D-IIDN biotransformation to D-IIMN at all time points. In addition, the rate of D-IIDN biotransformation was greater than that of L-IIDN at most IIDN concentrations tested. By contrast, the amount of D- and L-IIDN in the tissue was the same at all time points and concentrations tested, indicating that selective uptake of D-IIDN into blood vessels did not occur. When tissues were made tolerant to organic nitrate-induced relaxation by treatment with a high concentration of glyceryl trinitrate, the biotransformation of both D- and L-IIDN was attenuated. This suggests that mechanism-based biotransformation may be affected during tolerance development. Furthermore, the association of preferential D-IIDN biotransformation with its greater potency for vasodilation and cyclic GMP accumulation suggests than an enantioselective site for biotransformation is an important component of organic nitrate-induced vasodilation.Key words: biotransformation, vascular smooth muscle, organic nitrates, isoidide dinitrate, enantiomers.
Ductus arteriosus: involvement of a sarcolemmal cytochrome P-450 in O2 constriction?
Authors: Coceani Flavio , Wright Julie , Breen Carole
Published: April 2011

Our previous studies implicate a cytochrome P-450-based mechanism in the constrictor response of the ductus arteriosus to oxygen. The present experiments were conducted on saponin-skinned strips of ductal muscle from mature fetal lambs to determine the location, sarcolemmal versus intracellular, of this cytochrome and to obtain a better insight into the sequence of events underlying the action of oxygen. Skinned preparations contracted to free Ca2+ over the range between 0.1 and 5–10 μM (pCa 7 to 5). In contrast, oxygen (Po2, 608–690 Torr; 1 Torr = 133.3 Pa) had no significant effect, both in the absence and presence of 10 μM calcium. Carbon monoxide, tested as pure CO or a CO–O2 mixture (ratio 0.28), did not relax preparations maximally contracted with calcium. These findings indicate that oxygen exerts its effect on the plasma membrane of ductus muscle cells and that a membrane-bound cytochrome P-450 mechanism likely functions as the signal transducer for oxygen in the formation of a constrictor agent.Key words: ductus arteriosus closure, chemically skinned muscle, second messenger.
Modulation of the effects of sotalol on Purkinje strand electromechanical characteristics
Authors: Lathrop David A. , Varró András
Published: April 2011

The modulation of the effects of sotalol (30 μM) by two sodium channel blockers, tetrodotoxin (0.07 μM) and lidocaine (50 μM), and by a potassium channel activator, nicorandil (30 μM), were examined. Sotalol alone greatly increased Purkinje fiber transmembrane action potential duration and, in some preparations, induced early afterdepolarizations. Concurrent with the changes in action potential duration, sotalol also increased isolated Purkinje strand developed force paced at slow rates (0.33 Hz). These sotalol-induced alterations of Purkinje strand electromechanical characteristics were similar to those produced by either veratrine (0.6 or 1.0 μg/mL) or by tetraethylammonium (10 mM). The effects of sotalol on action potential duration and force development were reversed by exposure to either tetrodotoxin or nicorandil. Lidocaine also reversed the effects of sotalol on action potential duration and developed force. The sotalol-induced increase in action potential duration and development of early afterdepolarizations may, therefore, be abated by combination with drugs that either block cardiac sodium channels or that increase membrane potassium conductance. Combination with such drugs may help prevent the adverse arrhythmogenic effects of sotalol.Key words: sotalol, lidocaine, action potential duration, nicorandil, force development, tetrodotoxin.
Effects of increased perfusion pressure on medullary collecting duct function
Authors: Sonnenberg H. , Honrath U. , Wilson D. R.
Published: April 2011

The role of the medullary collecting duct in pressure natriuresis has not been established. In vivo microcatheterization was used to study the effect of an acute increase in blood pressure induced by bilateral carotid artery and vagal nerve ligation on medullary collecting duct function in anaesthetized rats. Increased fluid and electrolyte excretion during pressure natriuresis were accompanied by increased delivery of water, sodium, chloride, and potassium to the beginning of the medullary collecting duct, a change that was significantly greater than in a second series of time-control animals. These increases in delivery were within the range for which constant fractional NaCl reabsorption had been found previously. However, during increased perfusion pressure, reabsorption of both sodium and chloride in the medullary collecting duct as a fraction of delivered load were reduced from 81 ± 4.1 to 51 ± 9.3% (p < 0.01) and from 65.7 ± 6.0 to 42.7 ± 9.1% (p < 0.01), respectively. No significant changes in medullary collecting reabsorption were seen in the time controls. We conclude that increased perfusion pressure, in addition to increasing delivery to the medullary collecting duct, also inhibits sodium chloride reabsorption in this nephron segment.Key words: hypertension, vagotomy, collecting duct, sodium excretion, atrial natriuretic factor.
Dissociation between right atrial pressure and plasma atrial natriuretic factor following prolonged high salt intake
Authors: Widimsky Jr. Jiri , Kuchel Otto , Debinski Waldemar , Thibault Gaétan
Published: April 2011

The influence of prolonged high salt intake on intravascular volume, right atrial pressure, plasma atrial natriuretic factor, and extra-atrial tissue (lung, kidney, and liver) COOH- and NH2-terminal atrial natriuretic factor content was investigated in normotensive rats. Despite prolonged high salt (8% NaCl) intake for 5 weeks, total intravascular volume was not impaired. However, right atrial pressure was increased by 54% (p < 0.01) after salt loading. Although this increment in right atrial pressure should favor atrial natriuretic factor release after NaCl intake, plasma atrial natriuretic factor (COOH-terminal) concentrations markedly decreased from 97.8 ± 27 to 38.9 ± 8 pg/mL. Sodium and circulatory homeostasis was, however, well preserved. The lungs contained the highest levels of COOH- and NH2-terminal atrial natriuretic factor. Salt loading resulted in increased concentrations of low as well as high molecular weight atrial natriuretic factor in the lung but not in the kidney or the liver. Our study indicates a limited role of atrial natriuretic factor in adaptation to prolonged salt consumption in rats. Dissociation between right atrial pressure and plasma atrial natriuretic factor after salt intake implicates other factors regulating circulating peptide levels. Prolonged salt intake increases lung generation of atrial natriuretic factor.Key words: atrial natriuretic factor, volume, atrial pressure, high salt diet.
Inhibition kinetics of cationic drugs on N′-methylnicotinamide uptake by brush border membrane vesicles from the dog kidney cortex
Authors: Bendayan Reina , Sellers Edward M. , Silverman Melvin
Published: April 2011

The effect of cationic drugs on the uptake of the prototypical organic cation N′-methylnicotinamide has been evaluated. Using purified brash border membrane vesicles prepared from dog kidney cortex and applying a rapid Millipore filtration technique, cationic drugs apparent inhibitory constants (Ki) were calculated from kinetic analysis of N′-methylnicotinamide uptake corrected for noncarrier-mediated transport (10 s uptake; outwardly directed H+ gradient; pH 7.4, 25 °C). All of the cationic drugs tested exhibited competitive inhibition of N′-methylnicotinamide uptake suggesting that they all share the organic base transport system at the renal proximal tubule. The Ki values were as follows, in order of decreasing apparent affinity: quinidine (0.7 μM), trimethoprim (1.3 μM), cimetidine (2.0 μM), famotidine (3.0 μM), quinine (7.0 μM), amiloride (5.8 μM), procainamide (21 μM), and nizatidine (30 μM). The different relative affinities of the drugs for the organic base transport system may explain the mutual competition for renal tubular secretion observed when cationic drugs are administered concurrently in vivo, e.g., trimethoprim–procainamide and cimetidine–procainamide. The approach outlined in the present study should prove useful to predict complex drug interactions in clinical pharmacology.Key words: renal tubular secretion, membrane transport, cationic drugs, N′-methylnicotinamide.
Effect of furegrelate on renal plasma flow after angiotensin II infusion
Authors: Kaushal Ravi D. , Wilson Thomas W.
Published: April 2011

We had previously shown that selective thromboxane synthetase inhibition with furegrelate increases urinary excretion of 6-ketoPGF1α, the hydrolysis product of prostacyclin after stimulation of renal prostaglandin synthesis with furosemide. The present study assessed the functional significance of this "redirection" of prostaglandin formation using a more physiologic stimulus, angiotensin II. Sprague–Dawley rats (n = 27) were fitted with a transabdominal bladder cannula. Five days later they were given angiotensin II (10 mg∙kg−1∙min−1) by intravenous infusion. After 30 min, an infusion of furegrelate, 2 mg/kg, then 2 mg∙kg−1∙h−1, (n = 9); indomethacin, 2 mg/kg, then 2 mg∙kg−1∙h−1 (n = 9); or vehicle, 250 μL, then 0.018 mL/min (n = 9) was begun for 60 min. Clearance of [14C]para-aminohippuric acid was taken as a measure of renal plasma flow. Angiotensin II raised the mean arterial pressure in all groups. Administration of furegrelate or indomethacin did not change mean arterial pressure or heart rate. Angiotensin II reduced [14C]p-aminohippuric acid clearance by about 32% (1.42 ± 0.18 to 0.97 ± 0.07 mL∙min−1∙100 g−1, p < 0.05). Furegrelate attenuated this renal vasoconstriction (0.97 ± 0.07 to 1.38 ± 0.17 mL∙min−1∙100 g−1, p < 0.05), while indomethacin increased it by a further 32% (1.78 ± 0.12 to 1.20 ± 0.12 mL∙min−1∙100 g−1, p < 0.05). Vehicle alone had no effect. Furegrelate reduced serum thromboxane B2 by 90% (6.52 ± 0.030 to 0.7 ± 0.21 ng/100 μL, p < 0.05), while indomethacin reduced it by 73% (5.9 ± 0.99 to 1.4 ± 0.20 ng/100 μL, p < 0.05). We conclude that furegrelate attenuates the renal vasoconstriction of angiotensin II, presumably by enhancing the formation of vasodilator prostaglandins.Key words: angiotensin II, furegrelate, indomethacin, para-aminohippuric acid clearance.
Absorption of triglycerides in the absence of lipase
Authors: Chow B. P. C. , Shaffer E. A. , Parsons H. G.
Published: April 2011

Medium chain triglycerides are considered to be readily absorbed intact in the absence of pancreatic lipase, unlike long chain triglycerides. Commercial medium chain triglyceride oils comprise various medium chain fatty acids from 6 to 12 carbons in length resulting in triglyceride molecules of different sizes and molecular weights. The effect of molecular weight and hence fatty acid chain length on the efficiency of intact medium chain triglyceride absorption is unknown. Therefore, this study measured, using a single-pass marker perfusion technique, intestinal jejunum absorption of five medium chain and one long chain triglycerides in anesthetized Sprague–Dawley rats. The molecular weights of the five medium chain triglycerides were 470.7, 498.8, 526.8, 554.9, 639.0, and the long chain triglyceride, 885.4. Residual luminal pancreatic lipase was removed prior to lipid perfusion. This study demonstrated that medium chain triglycerides were absorbed in the absence of lipase whereas long chain triglyceride was not. There was no significant variation in the absorption of the five different medium chain triglycerides perfused. The molecular weight of the medium chain triglyceride did not affect its intact absorption by the small intestine.Key words: triglycerides, intestinal absorption, molecular weight, pancreatic lipase, fat.
Evidence against the role of α1-adrenoceptor reserve in buffering the inhibitory effect of nifedipine on the contractility of canine vascular smooth muscle
Authors: Guan Yong-Yuan , Kwan Chiu-Yin , Daniel Edwin E.
Published: April 2011

The relationship between the postsynaptic α1-adrenoceptor reserve and the sensitivity of vasoconstriction induced by α-adrenoceptor agonists to the dihydropyridine Ca2+ entry blocker nifedipine was investigated in isolated muscle strips of dog mesenteric artery (DMA) and saphenous vein (DSV). The amplitudes of the contractile responses of DMA induced by phenylephrine were the same as those in DSV in the presence and in the absence of extracellular Ca2+. The use of 3 × 10−9 M phenoxybenzamine to irreversibly block the α1-adrenoceptors revealed a marked difference in the size of the α1-adrenoceptor reserve between DMA (40%) and DSV (7%). In spite of a larger receptor reserve, the contractile responses induced by phenylephrine in DMA were more sensitive to nifedipine compared with those in DSV. These results suggest that the postsynaptic α1-adrenoceptor reserve in vascular smooth muscle, at least in DMA and DSV, does not play an important role in buffering the inhibitory effect of nifedipine on the contractile response to a full agonist of α1-adrenoceptors. Other factors, such as the difference in the membrane depolarizing effect, the ability to utilize intracellular Ca2+ for contraction, and the possible existence of α1-adrenoceptor subtypes, may contribute to the different inhibitory effects of nifedipine on these blood vessels.Key words: adrenoceptors, nifedipine, smooth muscle, calcium, saphenous vein, mesenteric artery.
Phencyclidine actions measured intracellularly in hippocampal CA1 neurons
Authors: Kujtan Peter W. , Carlen Peter L.
Published: April 2011

The electrophysiological effects of phencyclidine (PCP) were measured intracellularly in guinea pig hippocampal CA1 neurons in vitro. At all doses tested (0.2 μM – 10 mM), PCP increased the width of action potentials (APs). Doses of 10 μM and higher were associated with decreased action potential amplitude. PCP decreased inhibitory postsynaptic potentials and excitatory postsynaptic potentials but did not alter responses to focally applied GABA. At the lowest dose (0.2 μM), PCP decreased the input resistance (Rin), while at all other doses Rin was increased. PCP decreased post-spike train afterhyperpolarizations at low and medium doses. PCP effects persisted in low calcium medium and also in medium containing 10−6 M tetrodotoxin. It is concluded that in these central neurons, PCP primarily blocks potassium conductances at all doses and, at anesthetic doses, depresses sodium-dependent spikes.Key words: phencyclidine, potassium conductance, CA1 neurons, electrophysiology.
Effects of calcium channel antagonists on the vagally mediated cardiac chronotropic response in dogs
Authors: Wallick Don W. , Stuesse Sherry L. , Martin Paul
Published: April 2011

A brief electrical stimulation of the vagus nerve may elicit a triphasic response comprising (i) an initial prolongation of the same or the next cardiac cycle, (ii) a return of the subsequent cardiac cycle to about the level prior to vagal stimulation, and (iii) a secondary prolongation of cardiac cycle length that lasts several beats. We compared the effects of two calcium channel antagonists, verapamil and nifedipine, on this triphasic response to vagal stimulation in chloralose-anesthetized, open-chest dogs. In the absence of vagal stimulation, nifedipine (doses of 10, 40, and 50 μg/kg for a total dose of 100 μg/kg, i.v.) and verapamil (two doses of 100 μg/kg each, i.v.) increased the cardiac cycle length (A–A interval) by 16% (429 ± 20 to 496 ± 21 ms) and 29% (470 ± 33 to 605 ± 54 ms), respectively. Nifedipine (100 μg/kg total) attenuated the initial vagally mediated prolongation of the A–A interval, from 474 ± 19 to 369 ± 42 ms above the basal A–A interval. Following the initial prolongation of the vagal effect, other A–A intervals were not affected. In contrast, verapamil potentiated the vagally mediated initial prolongation in cardiac cycle length at the first dose administered (100 μg/kg) from 492 ± 17 to 561 ± 14 ms, but other increases in dosages had no further effect. Thus these two calcium channel antagonists have different effects on the sinoatrial chronotropic responses caused by brief vagal stimulation.Key words: autonomic control, parasympathetic, heart, calcium.
The effect of zinc levels in fetal circulation on zinc clearance across the in situ perfused guinea pig placenta
Authors: Paterson P. G. , Sarkar B. , Zlotkin S. H.
Published: April 2011

Although zinc is essential for normal fetal growth and development, little is known about factors that influence its transfer across the placenta. The in situ perfused guinea pig placenta model was used to study the influence of the zinc concentration of fetal circulation on maternofetal placental zinc transfer. A placenta of the anaesthetized sow was perfused (on the fetal side) with a physiological perfusate via the umbilical vessels, with the fetus excluded. The sow was infused intravenously with 65zinc as a tracer of placental Zn clearance, and with antipyrine as an indirect indicator of maternal placental blood flow. Maternal plasma and placental effluent samples collected at intervals were counted for 65zinc by gamma counter, and the absorbance of nitrosated antipyrine was measured at 350 nm. Varying the mean zinc concentration in the perfusate from 0.176 to 1.87 mg/L had no effect on relative zinc clearance calculated as zinc clearance/antipyrine clearance (mean ± SEM; 0.085 ± 0.010 vs. 0.114 ± 0.018; n = 6; p > 0.05). The results suggest that short-term changes in fetal zinc status do not influence placental zinc transfer.Key words: placenta, zinc, transport, trophoblast.
Calcium, calcium channels, and calcium channel antagonists
Authors: Triggle David J.
Published: April 2011

Voltage-dependent Ca2+ channels are an important pathway for Ca2+ influx in excitable cells. They also represent an important site of action for a therapeutic group of agents, the Ca2+ channel antagonists. These drugs enjoy considerable use in the cardiovascular area including angina, some arrhythmias, hypertension, and peripheral vascular disorders. The voltage-dependent Ca2+ channels exist in a number of subclasses characterized by electrophysiologic, permeation, and pharmacologic criteria. The Ca2+ channel antagonists, including verapamil, nifedipine, and diltiazem, serve to characterize the L channel class. This channel class has been characterized as a pharmacologic receptor, since it possesses specific drug-binding sites for both antagonists and activators and it is regulated by homologous and heterologous influences. The Ca2+ channels of both voltage- and ligand-regulated classes are likely to continue to be major research targets for new drug design and action.Key words: calcium, calcium channels, calcium antagonists, 1,4-dihydropyridines, channel regulation, receptor regulation.
Transitions among atrial fibrillation, atrial flutter, and sinus rhythm during procainamide infusion and vagal stimulation in dogs with sterile pericarditis
Authors: Pagé Pierre L. , Hassanalizadeh Hamid , Cardinal René
Published: April 2011

The mechanism of atrial flutter and fibrillation induced by rapid pacing in 22 dogs with 3-day-old sterile pericarditis was investigated by computerized epicardial mapping of atrial activation before and after administration of agents known to modify atrial electrophysiologic properties: procainamide, isoproterenol, and electrical stimulation of the vagosympathetic trunks. Before the administration of any of these agents, a total of 30 episodes of sustained atrial flutter (> 1 min duration, monomorphic; regular cycle length, 127 ± 12 ms, mean ± SD) was induced in 15 out of 22 dogs and 9 episodes of unstable atrial flutter (duration, <1 min; cycle length, 129 ± 34 ms; monomorphic, alternating with fibrillation) were induced in the remaining 7 preparations. In the latter, administration of procainamide transformed unstable atrial flutter and atrial fibrillation to sustained atrial flutter (cycle length, 142 ± 33 ms; n = 9 episodes). During control atrial flutter, atrial maps displayed circus movement of excitation in the right atrial free wall with faster conduction parallel to the orientation of intra-atrial myocardial bundles. Vagal stimulation changed atrial flutter to atrial fibrillation in 32 of 73 trials; this was associated with acceleration of conduction in the lower right atrium, leading to fragmentation of the major wave front. Isoproterenol produced a 6–25% increase of the atrial rate in 6 out of 14 trials of atrial flutter and induced atrial fibrillation in 4. After procainamide, the reentrant pathway was lengthened and conduction was slowed further in the right atrium. Maps obtained during unstable atrial flutter showed incomplete circuits involving the right atrium. Following procainamide infusion, the area of functional dissociation or block was enlarged and a stable circus movement pattern, which was similar to the pattern seen in control atrial flutter, was established in the right atrium. We conclude that (1) the transitions among atrial fibrillation, atrial flutter, and sinus rhythm occur between different functional states of the same circus movement substratum primarily located in the lower right atrial free wall, and (2) the anisotropic conduction properties of the right atrium may contribute to these reentrant arrhythmias and may be potentiated by acute pericarditis.Key words: atrial flutter, atrial fibrillation, atrial mapping, antiarrhythmic drugs, vagal stimulation.
Increased serum sulfate after protein loading in adult humans
Authors: Cole David E. C. , Thurgood Anne M. , Whiting Susan J.
Published: April 2011

To determine the effects of a protein loading on sulfate metabolism in humans, we monitored serum sulfate concentrations in 12 fasting adult volunteers fed a high-protein meal of egg white and an isocaloric low-protein meal. With each subject serving as his or her own control, we found that mean serum sulfate rose only slightly with the low-protein meal but was significantly higher with high-protein loading at 3 and 3.5 h. The median of the peak sulfate concentration was 57% greater than baseline with the high-protein meal versus 11% with no loading. Since changes in serum sulfate have been shown to influence the rate of sulfation for a variety of different acceptor molecules, these observations indicate a means by which protein feeding may simultaneously influence diverse metabolic pathways.Key words: serum sulfate, protein intake, sulfur metabolism, human dietary studies.
Effects of dexamethasone on the activity of histidine decarboxylase, ornithine decarboxylase, and DOPA decarboxylase in rat oxyntic mucosa
Authors: Araki Masataka , Nakamura Mitsuo , Takenoshita Seiichi , Shoda Hirokazu , Nagamachi Yukio , Matsuzaki Shigeru
Published: April 2011

Since accelerated turnover of histamine in oxyntic mucosa may be an important factor in the pathogenesis of peptic ulcers, the effect of dexamethasone and other glucocorticoids on the activity of gastric histidine decarboxylase (HDC) was studied in the rat. The activity of HDC in rat oxyntic mucosa increased significantly after dexamethasone was injected s.c. to rats at doses larger than 0.4 mg/kg body weight. The maximum response of the HDC activity to dexamethasone (4 mg/kg) was observed 8 h after the treatment. The activity of ornithine decarboxylase (ODC) increased at 4 h, while that of DOPA decarboxylase showed no significant change throughout the 16-h period following a single injection of dexamethasone. The mucosal levels of histamine, putrescine, and spermidine rose significantly after the steroid treatment, while the spermine levels remained nearly constant. There was no sex difference in these responses to dexamethasone. Betamethasone showed nearly the same effects as dexamethasone on the decarboxylase activities and the mucosal levels of diamines. Serum gastrin levels showed no significant change for the first 4 h and then rose significantly 8 and 16 h after dexamethasone treatment. Pentagastrin (0.5 mg/kg) increased the HDC activity, while it showed no significant effect on either the mucosal ODC activity or levels of polyamines and histamine. These data suggest that dexamethasone influences the metabolism of histamine and polyamines in rat oxyntic mucosa both directly and via stimulation of gastrin release.Key words: dexamethasone, betamethasone, oxyntic mucosa, histidine decarboxylase, ornithine decarboxylase, DOPA decarboxylase.
Measurement of starch absorption in humans
Authors: Strocchi Alessandra , Levitt Michael D.
Published: April 2011

Although starch provides a large fraction of human caloric intake, there is limited information concerning the efficiency of intestinal absorption of this nutrient. Owing to the fermentation of starch by colonic bacteria, there is no quantitative test for starch absorption comparable to the fecal fat determination. The most accurate estimation of starch absorption has been obtained by intubating the terminal ileum and aspirating ileal contents following ingestion of a meal containing starch plus a nonabsorbable marker. Starch absorption is calculated from the ratio of starch:marker in the ileal aspirate relative to the ratio in the meal. Disadvantages of the technique are the requirement for ileal intubation and the possible adverse effect of intubation on the absorptive process. A more widely used technique to assess starch absorption involves measurement of breath hydrogen (H2) excretion after ingestion of starch. Malabsorbed starch is fermented by colonic bacteria with liberation of H2 that is absorbed and excreted in expired air. This test is simple and noninvasive and can provide quantitative measurements of starch malabsorption. Application of this technique has demonstrated that 5–10% of starch in wheat, potatoes, and corn is not absorbed by healthy subjects, while rice starch is nearly completely absorbed.Key words: starch, absorption, hydrogen, breath test, malabsorption.
Role of depolarization and calcium in contractions of canine trachealis from endogenous or exogenous acetylcholine
Authors: Daniel E. E. , Jury J. , Serio R. , Jager L. P.
Published: April 2011

The relationships of the electrical to the mechanical responses of the canine trachealis muscle during stimulation of its cholinergic nerves or exposure to exogenous acetylcholine were recorded in the single or the double sucrose gap. At 27 °C, the responses to a train of stimuli consisted of a transient depolarization excitatory junction potential of 10–30 mV followed by fading oscillations and contractions. When stimulus parameters were varied in the single sucrose gap, contractions were more closely associated with the occurrence of and varied in duration with the oscillations rather than with the amplitude of the EJP. Acetylcholine superfused at a concentration of 10−6 M for 30 s caused a prolonged depolarization of 10–20 mV, but a much larger contraction than could be elicited by nerve stimulation. None of the responses to acetylcholine was significantly affected by the Ca channel antagonists, nifedipine, nitrendipine, or verapamil in Ca channel blocking concentrations. When tissues were exposed to a Ca-free medium, the excitatory junction potentials and oscillations rapidly disappeared, but the electrical and mechanical responses to acetylcholine persisted and only gradually disappeared with repetitive exposures. Furthermore, in a medium with normal Ca2+ in the double sucrose gap, depolarization by 10–15 mV with an applied current caused no contraction, and repolarization to the normal membrane potential during acetylcholine-induced contraction caused no relaxation. Tetraethylammonium ion (20 mM) depolarized the membrane, increased membrane resistance, and enhanced the secondary oscillations and contractions after field stimulation. No other K+-channel blocker tested (Ba2+, apamin, 4-aminopyridine, glibenclamide, charybdotoxin) had the effect of prolonging secondary oscillations. We concluded that acetylcholine under our conditions acted to release internal Ca2+ and that the depolarization was secondary to that release or an associated event. Moreover, contractile responses to released acetylcholine during field stimulation do not appear to depend significantly on the opening of voltage-dependent Ca channels. The secondary oscillations were closely related to contraction; they seemed to be modulated by the opening of tetraethylammonium-sensitive, possibly Ca2+-activated K+ channels. The physiological functions, if any, of the initial depolarization associated with acetylcholine released (excitatory junction potential) or added remain unclear.Key words: acetylcholine, tracheal smooth muscle, trachea, chloride channels, sucrose gap, potassium channels.
Intracellular cyclic AMP concentration modulates gap junction permeability in parturient rat myometrium
Authors: Sakai Nobuyoshi , Blennerhassett Michael G. , Garfield Robert E.
Published: April 2011

We investigated whether cell-to-cell coupling between myometrial cells of parturient rats is influenced by intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) concentration. To evaluate the coupling, we measured input resistance (R0) and injected Lucifer Yellow (LY) using microelectrode techniques. The intercellular spread of the dye was then observed. Longitudinal muscle strips from rat myometrium were exposed to isoproterenol, forskolin, or dibutyryl cAMP (DB-cAMP) to elevate cAMP. Isoproterenol (10−11–10−6 M) and DB-cAMP (10−5–10−3 M) hyperpolarized the resting membrane potential (Em) and increased R0 in a dose-dependent fashion. Forskolin (10−6 M) also hyperpolarized Em and increased R0. When LY was injected into a single cell, LY spread rapidly and extensively to neighboring cells in parturient control tissues, while LY transfer was completely blocked by any of the three agents at high concentrations. The increased R0 and blocked transfer of LY owing to these agents indicate that the cell-to-cell coupling was decreased both electrically and metabolically. Myometrial cells of parturient rats show increased number and size of gap junctions (GJs). The rapid and reversible decrease in coupling is interpreted to reflect the reduced permeability of GJs between the muscle cells because of an elevation of cAMP. Control of GJ permeability by this second messenger may be important for the physiological regulation of intercellular coupling and the extent of synchronizing and coordinating electrical, metabolic, and contractile activity in the uterine wall during pregnancy and parturition.Key words: adenosine 3′,5′-cyclic monophosphate, cell-to-cell coupling, gap junction permeability, rat myometrium.
Influence of low-flow infusion and magnesium on tissue necrosis during regional ischemia in the canine myocardium
Authors: Kingma Jr. J. G. , Qiu Y. , Hearse D. J.
Published: April 2011

Passive intracoronary perfusion of therapeutic agents has been used in the clinical setting to attenuate the effects of brief episodes of myocardial ischemia. The objective of this study was to assess the effects of low-flow coronary infusion with or without Mg2+ on tissue necrosis and cardiac hemodynamics after prolonged regional ischemia. In 33 anesthetized dogs (5 excluded during study), the left anterior descending coronary artery was occluded for 6 h. Dogs were assigned to three groups: the first group (n = 8) was subjected to 6 h coronary occlusion without low-flow perfusion (controls), the second group (n = 10) received a low-flow coronary infusion of Ringer's lactate (Mg2+-free), and the third group (n = 10) received a low-flow coronary infusion of Ringer's lactate plus Mg2+ sulfate (15 mM). Tissue necrosis was evaluated using tetrazolium staining and was normalized to the principal baseline predictors of infarct size including anatomic risk zone (microsphere autoradiography) and coronary collateral flow. In control hearts, infarct size comprised 51.1 ± 4.1% of the risk zone (40.8 ± 5.1% left ventricular cross-sectional area (LV)). In the Mg2+-free and Mg2+ groups, risk zone size was 17.3 ± 2.2 and 16.8 ± 1.8% LV (p < 0.05 vs. controls), while infarct size was 23.1 ± 3.1 and 24.9 ± 8.1% (p < 0.05 vs. controls), respectively. Coronary collateral flow in the endocardium was similar for all of the experimental groups; however, hearts subjected to ischemia with low-flow perfusion of Ringer's lactate demonstrated significantly higher epicardial coronary collateral flow levels compared with controls. Our findings demonstrate that low-flow infusion of Ringer's solution (with or without Mg2+) into the ischemic zone produced significantly smaller infarcts; however, after 6 h of ischemia we could not demonstrate an additional beneficial effect of Mg2+.Key words: myocardial ischemia, infarct size, low-flow passive perfusion, Mg2+.
Diabetic type of cardiomyopathy in food-restricted rats
Authors: Savabi Fatemeh , Kirsch Arlene
Published: April 2011

We have demonstrated that food restriction that is associated with weight loss can produce a type of cardiac dysfunction similar to that produced by diabetes. As in diabetic atria, the food-restricted atria had a 2-fold increase in contraction force, rate of force development, and rate of force decline compared with controls. Both food-restricted and diabetic atria could tolerate anoxia better than controls. The contractile function of the whole perfused heart from the food-restricted rat was reduced, as in the case of the diabetic heart. As the left ventricular volume was increased, the left ventricular developed pressure and the rate of rise and fall in pressure were significantly reduced in both food-restricted and diabetic hearts, compared with those of age- and weight-matched controls. The positive inotropic responses of atria and whole perfused heart to increasing concentrations of extracellular calcium were similarly altered in food-restricted and diabetic hearts. The possible molecular mechanisms of these findings and some of the differences observed between food-restricted and diabetic hearts are discussed.Key words: diabetes, heart, cardiomyopathy, calorie restriction, high energy phosphate, creatine kinase.
Protein kinase C mediated activation and phosphorylation of Ca2+ pump in cardiac sarcolemma
Authors: Qu Yi , Torchia Joseph , Sen Amar Kumar
Published: April 2011

The effects of purified protein kinase C (PKC) on the Ca2+-pumping ATPase of cardiac sarcolemma were investigated. The addition of PKC to sarcolemmal vesicles resulted in a significant increase in ATP-dependent Ca2+ uptake, by increasing the calcium affinity by 2.8-fold (Km 0.14 vs. 0.4 μM for control) and by increasing Vmax from 5 to 6.8 nmol∙mg protein−1∙min−1. The addition of PKC also stimulated Ca2+ ATPase activity in sarcolemmal preparations. This activity was increased further upon the addition of calmodulin. These results suggest that PKC stimulates Ca2+ ATPase through a kinase-directed phosphorylation. The addition of PKC to a purified preparation of Ca2+ ATPase in the presence of [γ-32P]ATP resulted in a 100% increase in phosphorylation that was dependent on the presence of Ca2+, phosphatidylserine, and phorbol 12,13-dibutyrate. These results demonstrate that the Ca2+ ATPase of canine cardiac muscle can be phosphorylated by PKC in vitro, resulting in increased affinity of the Ca2+ ATPase for Ca2+ and increase in the Ca2+ pump pumping rate. The results suggest that the Ca2+-pumping ATPase in heart tissue can be stimulated by PKC, thereby regulating the intracellular Ca2+ levels in whole heart.Key words: protein kinase C, phosphorylation, plasma membrane, Ca2+ ATPase, heart.
Regulation of lipoprotein lipase activity in cardiac myocytes from control and diabetic rat hearts by plasma lipids
Authors: Rodrigues Brian , Braun Janice E. A. , Spooner Michael , Severson David L.
Published: April 2011

The objective of this investigation was to test the hypothesis that the diabetes-induced reduction in lipoprotein lipase activity in cardiac myocytes may be due to hypertriglyceridemia. Administration of 4-aminopyrazolopyrimidine (50 mg/kg) to control rats for 24 h reduced plasma triacylglycerol levels and increased the heparin-induced release of lipoprotein lipase into the incubation medium of cardiac myocytes. The acute (3–5 days) induction of diabetes by streptozotocin (100 mg/kg) produced hypertriglyceridemia and reduced heparin-releasable lipoprotein lipase activity in cardiac myocytes. Treatment of diabetic rats with 4-aminopyrazolopyrimidine resulted in a fall in plasma triacylglycerol content and increased heparin-releasable lipoprotein lipase activity. Administration of Triton WR-1339 also resulted in hypertriglyceridemia, but the heparin-induced release of lipoprotein lipase from control cardiac myocytes was not reduced in the absence of lipolysis of triacylglycerol-rich lipoproteins. Treatment with Triton WR-1339 did, however, increase the heparin-induced release of lipoprotein lipase from diabetic cardiac myocytes. Preparation of cardiac myocytes with 0.9 mM oleic acid resulted in a decrease in both total cellular and heparin-releasable lipoprotein lipase activities. These results suggest that the diabetes-induced reduction in heart lipoprotein lipase activity may, at least in part, be due to an inhibitory effect of free fatty acids, derived either from lipoprotein degradation or from adipose tissue lipolysis, on lipoprotein lipase activity in (and (or) release from) cardiac myocytes.Key words: diabetes, plasma triacylglycerols, cardiac myocytes, lipoprotein lipase.
Sensory irritation response in mice to sulfur dust
Authors: Bevan Christopher , Whitman Frederick T.
Published: April 2011

The potential of sulfur dust to produce sensory irritation was evaluated in mice. Male Swiss–Webster mice were exposed by head-only inhalation to 106, 263, or 451 mg/m3 sulfur dust aerosol at room temperature. Breathing frequency and patterns were monitored before, during, and after exposure to evaluate the animal's sensory irritation response to the test atmosphere. Group average breathing rates were decreased 7 and 17% below pretest values in mice exposed to 106 and 263 mg/m3, respectively; however, breathing patterns appeared normal, indicating that there was no sensory irritation. Mice exposed to 451 mg/m3 showed an increase in breathing frequency of 7%, with 1/4 mice displaying very slight signs of pulmonary (deep lung) irritation. Some of the mice in the low- and high-dose groups exhibited signs of slight eye irritation immediately after exposure, but all mice were normal 1 day later. On the basis of these findings, exposure to sulfur dust up to 451 mg/m3 did not produce any sensory or upper airway irritation in mice.Key words: sensory irritation, sulfur dust, dust aerosol.
Effect of lithium chloride on ornithine decarboxylase activity in rat adrenal
Authors: Strümpfer Alessandra , Hsiao Jerry , Peng Ted , Richards James
Published: April 2011

The effects of lithium chloride on ornithine decarboxylase (ODC) activity were compared in the adrenal and kidney of control (saline treated) and prolactin-treated rats. ODC activity was decreased in kidney of both groups of animals, the magnitude of the effect of lithium in the hormone-treated group varying with the time of administering the lithium relative to prolactin. The response in the adrenal was quite different. Following treatment with LiCl, there was a gradual increase in ODC activity from a low of 10–35 pmol CO2∙30 min−1∙mg protein−1 in control animals to values 20- to 30-fold greater at 5 h. In rats treated simultaneously with LiCl and prolactin, ODC activity was greater at 5 h than that observed in animals receiving either compound alone, indicating that their effects were additive. When LiCl was given 4 h after prolactin, i.e., 1 h before sacrifice, ODC activity decreased to a very low level at 5 h, as in other tissues. The increase in ODC activity in the adrenal following LiCl is of the same magnitude as the changes observed in tissues stimulated to undergo alterations in proliferation, differentiation, or metabolic or membrane activity by hormones and other external stimuli.Key words: ornithine decarboxylase, rat adrenal, effects of lithium.