bluuebunny/crossref_metadata_2025 huggingface dataset:
Epileptiform seizures in domestic fowl. VII. Plasma phenytoin concentrations and anticonvulsant activity
Authors: Davis H. L. , Johnson D. D. , Crawford R. D.
Published: April 2011

Acute dose–response studies with phenytoin were conducted to determine the relationship between plasma levels and anticonvulsant effect in epileptic chickens. Phenytoin produced statistically significant reductions in both the incidence and severity of seizures in photosensitive epileptic chickens when the plasma concentrations exceeded 8.15 ± 0.89 μg/ml. A high correlation exists between plasma phenytoin concentrations and both the reduction in incidence or severity of seizures. However, the appearance of plasma concentration dependent neurological toxicities resulted in a failure to achieve complete protection against intermittent photic stimulation induced seizures.
Effect of the external concentrations of potassium and sodium on the release of (−)-[3H]noradrenaline from the adrenergic nerves of the rat vas deferens
Authors: Johns A. , Paton D. M.
Published: April 2011

The effect of the external concentrations of sodium and potassium on the nerve-induced release of (−)-[3H]noradrenaline from the adrenergic nerves of the rat vas deferens has been investigated. Increasing the external potassium concentration above 5 mM decreased the amount of noradrenaline released, while reducing the external potassium concentration below 5 mM had no significant effect on the induced release of noradrenaline. Decreasing the external sodium concentration below 75 mM progressively decreased the release of noradrenaline. It is concluded that the amplitude of the action potential is optimum for release at the normal resting membrane potential, and only decreasing the amplitude of the action potential alters the amount of transmitter released per nerve impulse.
Vasoactive intestinal polypeptide excitation of central neurons
Authors: Phillis J. W. , Kirkpatrick J. R. , Said S. I.
Published: April 2011

Vasoactive intestinal polypeptide (VIP) was tested on neurons in the rat sensory motor cerebral cortex and on the isolated hemisected toad spinal cord. Iontophoretically applied VIP excited deep, spontaneously active cortical neurons, including identified corticospinal neurons. The excitation had a latency of onset varying from several seconds to over 1 min and often lasted for a minute or longer after cessation of the application. Desensitization of the effect occurred with repeated applications. VIP caused a depolarization of motoneurons and dorsal root terminals in the isolated amphibian spinal cord. Threshold for this effect was about 10−6 M. The effects of VIP on both preparations were comparable with those of another peptide, substance P.
Reflex effects of thoracic aorta wall stretch on regional vascular resistance
Authors: Szeto Peter M. , Lioy Franco
Published: April 2011

In anesthetized, vagotomized cats with both carotid arteries occluded, a stretch of the walls of the thoracic aorta, performed without obstructing aortic flow, induced a significant reflex increase in arterial pressure (35 ± 2−26 ± 1 mmHg; systolic–diastolic). This pressure increase was accompanied by significant increases in peripheral resistance in the superior mesenteric (+30%), renal (+23%), and external iliac (+23%) vascular beds. The increase in iliac resistance observed in the skinned leg was comparable with that observed in the contralateral intact limb. All these vascular responses were drastically reduced by the administration of phenoxybenzamine. After α-adrenergic blockade no signs of reflex vasodilatation could be detected during aortic stretch in any of the vascular beds examined.
Development of cardiovascular responses to sympathomimetic amines and autonomic blockade in the unanesthetized fetus
Authors: Harris W. H. , Petten G. R. van
Published: April 2011

The cardiovascular effects of phenylephrine or ephedrine alone and after autonomic blockade were studied in the chronically cannulaied fetal lamb (100–145 days), the newborn lamb, and adult sheep. As gestation advanced, phenylephrine and ephedrine produced an increasing pressor response before and after pretreatment with atropine (1 mg/kg). Compared with the fetus, the magnitudes of the pressor responses were somewhat greater in the newborn and much larger in the adult. Both drugs produced a reflex bradycardia in the unatropinized fetus which in the case of ephedrine was followed by a tachycardia. Pretreatment with atropine resulted in an immediate tachycardia after ephedrine but not after phenylephrine administration. Pretreatment with phentolamine (0.15 mg/kg) produced about a 55% inhibition of the phenylcphrine pressor response in both the fetus and adult, suggesting a linear relationship between body weight and number of α-adrenergic receptors. Pretreatment with metoprolol blocked the tachycardia associated with ephedrine administration to unatropinized fetuses. In summary, the increase in the magnitude of the pressor response to phenylephrine suggested development of the receptor–effector system. The greater development of the response to ephedrine suggested that there was an increasing amount of noradrenaline being released with advancing gestation.
Validation of a single-compartment approach to the calculation of secretion rates of ACTH
Authors: Cowan John S.
Published: April 2011

A single-compartment model used in this laboratory for continuously calculating ACTH secretion rates from measured plasma ACTH concentrations has been tested for its ability to follow changing rates of ACTH entry (rapid departure from steady state). ACTH was infused at known moderately high but physiological rates into anaesthetized dogs (Nembutal). Under such conditions endogenous secretion is initially <5% of infused rates. Orthogonal polynomials (ACTHt) were fitted to plasma ACTH vs. time data. Then [Formula: see text] where it was previously shown that the metabolic clearance rate of ACTH (MCR) lacked significant inter-animal or concentration-dependent variation, and its distribution volume (V) was also constant.The calculated ACTH entry rate curves (a) followed a 10-fold increase in infusion rate over 4 min and subsequent rapid decline with a lag of only about 1 min and, despite some blurring, gave an integrated response equal to 94 ± 5.5% of the known signal, and (b) followed a sinusoidal change in infusion rate (amplitude, 1.7 × base rate; period, 40 min) with a few percent error and negligible lag. These signals imitate (a) an abrupt stress response, and (b) other rapid departures from steady state.
Assessment of ether anesthesia in normal and spinal cats using gas–liquid chromatographic analysis of blood
Authors: Sitar Daniel S. , Čapek Radan , Zorychta E.
Published: April 2011

A new gas–liquid chromatographic method was developed for the determination of diethylether in whole blood. Ether was quantitated by peak area ratio analysis with n-propanol as the internal standard using a flame ionization detector. Blood ether concentrations were determined in cats undergoing inhalational anesthesia by ether in oxygen. In normal spontaneously breathing cats, anesthesia began at ether concentrations of about 0.6 g/ℓ, and respiratory arrest occurred at 2.4 g/ℓ and above. Mean arterial blood pressure was well maintained throughout the entire anesthetic range. In spinal artificially respired animals, mean arterial blood pressure correlated inversely with blood ether concentration. The data suggest that decline in blood pressure may be a useful sign of ether toxicity in spinal cats.
Effect of neomycin on amino acid uptake and on synthesis and release of lipoproteins by rat intestine
Authors: Kessler Jacques I. , Sehgal Ashok K. , Turcotte Rolland
Published: April 2011

The in vitro uptake and incorporation of amino acids into proteins and lipoproteins, and release of lipoproteins by intestinal segments of control and rats treated with neomycin or its N-methylated and N-acetylated derivatives (1 mg/10 g body weight for 8 days) was investigated. The intestine of the neomycin-treated rats contained a greater amount of water within the epithelial cells (81.6 ± 6.2% vs. 89.3 ± 6.8%, P < 0.01) and it exhibited a significantly greater uptake of amino acid radioactivity per weight of tissue proteins (1.9 ± 0.2% vs. 2.6 ± 0.3%, P < 0.001). The fraction of the amino acid radioactivity incorporated into tissue proteins was not affected by the respective treatments. The distribution of the radioactivity associated with tissue lipoproteins, however, was markedly affected by neomycin. The radioactivity of tissue low density lipoproteins (LDL) and high density lipoproteins (HDL) of the neomycin-treated rats was much lower than that of the controls. This difference could be accounted for by the release of a greater proportion of LDL and HDL radioactivity in the incubation medium. Release of LDL and HDL radioactivity was inversely related to the molecular weights of these lipoproteins. The effects of neomycin were reproduced by its N-methylated derivative which is devoid of antibiotic activity but retains the polycationic properties of neomycin. The N-acetylated derivative which is devoid of both antibiotic and polycationic properties was without effect. These findings suggest that the observed effects may be related to the polycationic properties of neomycin and that they are independent of its antibiotic activity.
Urinary sodium, phosphate, and hydrogen excretion following unilateral kidney clamping
Authors: Plante Gérard E. , Hermkens Hubert
Published: April 2011

The influence of extracellular volume on compensatory adaptation of sodium, phosphate, and hydrogen excretion after unilateral kidney exclusion was examined in the dog. Ammonium chloride was administered to all animals to raise urinary hydrogen excretion. Eleven dogs (group I) were studied under relative hydropenia and 11 (group II) were volume expanded with isotonic NaCl. Six animals (group III) prepared as group II were sham operated.In groups I and II, plasma bicarbonate decreased by 1.1 and 1.2 mM/ℓ after unilateral kidney clamping, while serum phosphate rose from 5.3 to 6.1 and from 3.6 to 3.9 mg%, respectively. The following parameters are those obtained from the left kidney before and after contralateral clamping. Urinary sodium remained unchanged after clamping in group I but rose from 422 to 681 μequiv./min in group II. In contrast, urinary phosphate increased from 83 to 233 and from 94 to 189 μg/min in groups I and II, respectively.Measured titratable acid and urinary ammonium excretion remained unchanged in group I. A small but significant decrement in ammonium was obtained with time in group II. Glomerular filtration and renal plasma flow were not influenced by contralateral clamping, but filtration fraction was lower in group II than in group I. No change occurred in group III.Extracellular volume appears to play a critical role in the physiological expression of contralateral natriuresis after unilateral clamping whereas compensatory phosphaturia is obtained in both hydropenic and volume-expanded animals.
Nipecotic acid and 2,4-diaminobutyric acid enhance the actions of muscimol on cerebral cortical neurons
Authors: Yarbrough G. G.
Published: April 2011

Iontophoretically applied muscimol exerted a potent inhibitory action on the firing of spontaneously active cerebral cortical neurons of rats. On the basis of ejection currents employed, muscimol was considerably more potent than γ-aminobutyric acid (GABA), and the inhibitions produced by muscimol were frequently of a longer duration than those observed with GABA. Nipecotic acid and diaminobutyric acid (DABA) are potent inhibitors of high-affinity GABA uptake systems and muscimol is not thought to be a substrate for high-affinity GABA uptake (JOHNSTON, G. A. R. 1976. Physiolic pharmacology of GABA and its antagonists in the vertebrate nervous system. In GABA in nervous system function. Edited by E. Roberts, T. Chase, and D. B. Tower. Raven Press, New York). However, nipecotic acid and DABA consistently enhanced the inhibitory effects of both GABA and muscimol on cortical neurons while not affecting monoamine or adenosine 5′-monophosphate induced inhibitions. These findings suggest that iontophoretically applied nipecotic acid and DABA have some specificity for amino acid mechanisms in the cortex, but their actions appear to be more complex than can be explained by a selective blockade of GABA uptake processes. Thus, the uptake blockers may be exerting a weak and not readily detectable agonist action at amino acid receptors. Alternatively, the actions of iontophoretically applied muscimol may be partially terminated by uptake through GABA uptake systems.
Some effects of the ionophore X-537A on the isolated rat tail artery
Authors: Palatý Vladimír , Todd Mary E.
Published: April 2011

The effects of micromolar concentrations of the ionophore X-537A (RO 2-2985) were studied using isolated preparations of the rat tail artery. The ionophore causes complete release of catecholamines from adrenergic nerves, which is the sole cause of the transient contractile response. The amines are released by a nonexocytotic process which seems to be related to the ability of X-537A to act as an efficient transmembrane carrier of Na+, K+, and H+ The ionophore also causes an almost complete and irreversible loss of the cocaine-sensitive component of metaraminol uptake by the tissue. X-537A dissipates the transmembrane concentration gradients of Na and K in the smooth muscle component of the preparation. This effect is unrelated to the release of endogenous catecholamines, and it can also be observed after the Na pump has been inhibited with ouabain. It is fully reversible, though not readily, and it can be induced repeatedly. In catecholamine-depleted strips, X-537A dissipates the transmembrane Na+ and K+ gradients without causing any change in tension. Stimulation of the rate of O2 consumption by X-537A in catecholamine-depleted tissue is reversible, and it is unaffected by ouabain and (or) removal of external Ca2+.
The effect of taurine on kindled seizures in the rat
Authors: Burnham W. M. , Albright P. , Racine R. J.
Published: April 2011

Recently, it has been reported that taurine, an amino acid with anticonvulsant properties, does not suppress experimental seizures generated by the 'kindling' technique. This finding seems somewhat paradoxical since taurine antagonizes other sorts of experimental convulsion and since kindled seizures are easily suppressed by other anticonvulsant drugs. Further tests were therefore conducted during which taurine's anticonvulsant effects were assessed: (1) when kindling stimulation was dropped to near-threshold levels; (2) when cortical as well as limbic kindled foci were stimulated; (3) when developing as well as fully kindled seizures were involved; and (4) when taurine was introduced directly into the ventricles of the brain. Even in these tests which were specifically designed to favour the appearance of anticonvulsant effects, no taurine antagonism of kindled seizures was found.
Dantrolene blocks intracellular calcium release in smooth muscle: competitive antagonism of thromboxane A2
Authors: Ally A. I. , Horrobin D. F. , Manku M. S. , Morgan R. O. , Karmazyn M. , Karmali R. A. , Cunnane S. C.
Published: April 2011

Dantrolene sodium has been shown to block the release of intracellular calcium in skeletal muscle. It has been proposed that dantrolene blocks the movement and (or) action of a natural calcium ionophore. In a rat vascular preparation dantrolene was found to inhibit pressor responses to noradrenaline and angiotensin but not those to potassium with an IC50 concentration within the therapeutic levels in man. Imidazole, an inhibitor of thromboxane A2 (TXA2) synthesis, had similar actions to dantrolene. Interactions between imidazole and dantrolene suggested that dantrolene may be a competitive antagonist of TXA2 in muscle. We report the first demonstration of an effect of dantrolene sodium on smooth muscle contractility and suggest that TXA2 is an essential modulator of vascular reactivity. A similar role has been shown for TXA2 in platelets.
The distribution of calcium in hypoxic cat hearts: the effect of β1-blockade
Authors: Pang Cathy C. Y. , Bailey Leslie E.
Published: April 2011

Contractile activity decays rapidly during the first few minutes of hypoxia in the mammalian myocardium. These changes may be the result of redistribution of the Ca involved in the excitation–contraction (E–C) coupling mechanism. It was the purpose of this study to determine if distortions in the Ca pool(s) involved in E–C coupling are responsible for the acute reduction in contractile force in the heart. Working, Langendorff kitten heart preparations were perfused with a Krebs–Henseleit solution equilibrated with 5% O2, 5% CO2, and 90% N2. Within 3 min of initiation of this treatment the Ca content of a pool directly involved in E–C coupling (Ca2) was reduced by approximately one-half, and this was accompanied by an equivalent increase in a slowly exchanging Ca pool (Ca3). A concomitant reduction in contractile force was associated with this redistribution of Ca. The Ca remaining in the heart after contractility had been abolished by Ca-free perfusion (residual tissue Ca) was significantly elevated by hypoxia. The β1 blocking agent practolol (10−5 M), prevented the hypoxia-induced reduction in Ca content of Ca2 produced by hypoxia, but had no effect on contractility under hypoxic conditions or during re-oxygenation. Practolol did not prevent the increase in residual tissue Ca induced by hypoxia. It was concluded that the immediate reduction in contractility caused by hypoxia was not causally related to the reduction in the quantity of Ca in Ca2, the pool involved in E–C coupling, but may be related to a rapid decrease in the supply of energy for contraction.
Spontaneous hydrolysis of heroin in buffered solution
Authors: Smith Paul T. , Hirst M. , Gowdey C. W.
Published: April 2011

Electron-capture gas–liquid chromatography was used to study the spontaneous hydrolysis of heroin in phosphate buffer (pH 6.4 and pH 7.4) at 23 °C. Aliquots of solution were taken over a 24-h period. After extraction at pH 8.9 into propan-2-ol (10%) – ethyl acetate, deacetylated products were made into heptafluorobutyrate derivatives which were analyzed quantitatively using nalorphine as the internal standard. Heroin decomposes to O6-monoacetylmorphine (O6-MAM) under these conditions. Further decomposition to morphine was not observed. Spontaneous hydrolysis was faster at pH 7.4 (first-order rate constant, 9.6 × 10−5 min−1) than at pH 6.4 (first-order rate constant, 3.0 × 10−5 min−1). In 24 h, the decomposition to O6-MAM was 13 and 4%, respectively.
Role of creatine phosphokinase in cellular function and metabolism
Authors: Saks V. A. , Rosenshtraukh L. V. , Smirnov V. N. , Chazov E. I.
Published: April 2011

This paper summarizes the data concerning the role of the creatine phosphokinase system in muscle cells with main attention to the cardiac muscle. Creatine phosphokinase isoenzymes play a key role in the intracellular energy transport from mitochondria to myofibrils and other sites of energy utilization. Due to the existence of the creatine phosphate pathway for energy transport, intracellular creatine phosphate concentration is apparently an important regulatory factor for muscle contraction which influences the contractile force by determining the rate of regeneration of ATP directly available for myosin ATPase, and at the same time controls the activator calcium entry into the myoplasm across the surface membrane of the cells.
Cryoactivation and tryptic activation of blood 'prorenin' in normal man and animals
Authors: Osmond D. H. , Cooper R. M.
Published: April 2011

Plasma and serum of healthy subjects apparently contain a precursor form of renin, or 'prorenin,' which can be activated by the ice-cold temperature at which samples are customarily handled for prolonged periods in laboratories and blood banks. The effect of such prior cryoactivation for 9 days at 4 °C is to increase subsequent plasma renin activity (PRA) at 37 °C by 108 ± 16.3% (mean ± SE) over the nonactivated control value (P < 0.001). At a lower temperature (−4 °C), the cryoactivation effect is considerably greater than at 4 °C. Cryoactivation is not obliterated by the prefreezing of plasma, or reduced by inclusion of bacteriostats. Nor is it attributable to any detectable reduction in angiotensinase activity. In rats, cryoactivation at 4 °C is much lower than in humans, suggesting a marked species difference either in prorenin concentration or in the rapidity of its spontaneous conversion after blood collection. Trypsin at near-optimal concentrations also consistently activates human plasma prorenin, whether at 4, 23, or 37 °C indicating that cold is not an essential concomitant of tryptic activation. In excess, the magnitude of which varies among individuals, trypsin at first produces activation and later a decline in PRA, probably due to degradation of the reactants (prorenin, renin, angiotensinogen) and of the initial product (angiotensin I). The identity of angiotensin I in activated and control plasmas can be established by specific radioimmunoassay, and bioassay. Our data indicate that tryptic activation involves little direct production of angiotensin I but rather converts prorenin, thereby enhancing the angiotensin generating capacity of the plasma renin system itself. Tryptic activation in plasma of anaesthetized dogs is lower than in humans, but higher than in conscious or anaesthetized rabbits in whom the effect appears to be slight. In anaesthetized rats there is virtually no tryptic activation, which is in line with the results by cryoactivation. Since the renin–angiotensin systems of dogs, rabbits, and rats have been extensively studied in experimental models of human hypertension, these observed departures from human levels of cryoactivation and tryptic activation of prorenin deserve further investigation.
Effect of renal denervation on the development of hypertension in spontaneously hypertensive rats
Authors: Kline R. L. , Kelton P. M. , Mercer P. F.
Published: April 2011

The involvement of the renal nerves in the development of hypertension in Okamoto spontaneously hypertensive rats (SHR) was investigated by performing bilateral renal denervation in a group (n = 7) of SHR at 8 weeks of age. A sham-operated group (n = 7) of SHR served as surgical controls. Systolic arterial pressure was recorded twice a week until 14 weeks of age using a tail cuff method. Renal denervation significantly (P < 0.01) altered the time course for development of hypertension, although both groups eventually developed hypertension. During the 6-week observation period, there were no significant differences in body weight, average 24-h food and fluid intake, urine output, or Na+ and K+ excretion between the two groups. At 20 weeks of age there were no significant, differences in systolic pressure, average fluid intake, or urine output between the sham and denervated groups. These results suggest that the renal nerves may be involved in the early phase of development of hypertension in the SHR. The possibility that altered renal function may be the mechanism of the above effects is discussed.
Brain extracellular potassium and genera anaesthetics
Authors: Morris M. E.
Published: April 2011

General anaesthetic agents (halothane, trichlorethylene, methohexital, pentobarbital, and alphaxalone–alphadolone) depress the extracellular accumulations (ΔEk) and associated focal potentials (ΔV) which are evoked in the cuneate nucleus by tetanic stimulation of peripheral nerves. Depressions of ΔV are significantly greater than those of ΔEk; at the same time there is a dissociation of the relation between ΔV and ΔEk. There are no detectable changes in the resting levels of K+ or the small voltage shifts evoked by low-frequency intranuclear stimulation with a microelectrode. When anaesthesia produces severe hypotension, augmentations of [K+]0 occur which can be attributed to depression of electrogenic Na–K pumping. A possible explanation of the reduction in K+ release resulting from afferent fibre activity would be failure of conduction caused by membrane stabilization or hyperpolarization.
Atropine blockade of cholinergic drugs on rabbit stomach muscle
Authors: Spero L.
Published: April 2011

The competition between atropine and a full agonist, carbachol, was tested on dibenamine-pretreated smooth muscle of rabbit stomach. Even after extensive irreversible blockade by dibenamine, atropine blockade of the response to carbachol was still competitive and the atropine affinity constant was unchanged. This differed from the noncompetitive action of atropine in blocking the contractile effects of partial agonists such as pilocarpine or heptyl trimethylammonium. The results thus indicate that it is not possible to convert a full agonist into a partial agonist merely by reducing the number of available cholinergic receptors.The present study compares the competitive effect of atropine on the actions of the full agonist carbachol, under conditions of irreversible blockade, with the competitive effect of atropine on partial agonists such as pilocarpine or heptyl trimethylammonium.
The effect of clothing on the initial ventilatory responses during cold-water immersion
Authors: Martin Sheilagh , Diewold R. J. , Cooper K. E.
Published: April 2011

The effect of clothing on ventilatory responses during cold-water immersion was studied. Subjects were immersed in water at 13.9 °C on two occasions wearing either a bathing suit only or clothed with jacket, shirt, pants, and sports shoes. It was found that the initial gasp and subsequent minutes of expired ventilation were significantly attenuated, whereas the changes in end-tidal [Formula: see text] were only significantly different for the 2nd and 3rd min of the immersion. It would appear that the use of clothing may prove beneficial during the first few minutes of a cold-water immersion by decreasing the powerful drive to increased respiration.
A new approach to the measurement of glycerol turnover
Authors: Kallai-Sanfaçon M. A. , Norwich K. H. , Steiner G.
Published: April 2011

These studies describe a new method, using a single bolus injection of labelled glycerol, to measure glycerol turnover. In a series of experiments utilizing single animals, this new approach was compared with the previously used method of constant tracer infusion. The two gave identical results. In the bolus method, once the time of maximum glycerol specific activity had been established, glycerol turnover could be calculated using very few additional data points obtained over a very short time span. This simplification was possible because the decay of glycerol specific activity was found to conform to a straight line on a plot of the logarithm of the specific activity versus the logarithm of the time. This new approach should simplify the measurement of glycerol turnover and should permit the determination of the rate of glycerol transformation to other end products.
Opiate-like, naloxone-reversible effects of androsterone sulfate in rats
Authors: LaBella Frank , Havlicek Viktor , Pinsky Carl , Leybin Leonid
Published: April 2011

Androsterone sulfate (5α-androstan-3α-ol-17-one, 3-sodium sulfate) administered to freely moving rats via cerebroventricular cannulae induced analgesia, wet-dog shakes, body jerks, rigidity, Straub tail, hypermotility, excessive grooming, hyperreactivity to stimuli, aggression, escape behavior, EEG spiking, and behavioral and EEG seizures. These responses resemble those produced by certain opiate drugs and by beta-endorphin, an endogenous peptide; they appear during the 5-min infusion period, persist in some cases for several hours, and are diminished by pretreatment with the narcotic antagonist naloxone. These findings indicate that steroid hormones can act upon at least some of the same central pathways influenced by recognized opiate compounds.
Hepatic glucose balance in response to direct stimulation of sympathetic nerves in the intact liver of cats
Authors: Lautt W. Wayne , Wong Chong
Published: April 2011

Changes in hepatic glucose balance in response to direct stimulation of the hepatic nerves were measured in cats. Simultaneous measurements were made of glucose concentrations entering and leaving the intact liver; this, combined with measured blood flows, allows calculation of hepatic glucose balance. Stimulation of the hepatic sympathetic nerves (8 Hz, 15 V, 1 ms) produced a rapid increase in hepatic glucose output that was statistically significant after 1 min and reached a peak 3–5 min after onset of stimulation, after which time the output declined somewhat. The half time for deactivation of the response was 1.8–2 min. Variability in the responses was largely accounted for by the variable control base lines measured immediately prior to stimulation. Those animals showing the highest basal output showed the least increase in output in response to the nerves. The response to stimulation of the mixed nerve trunk in the presence and absence of atropine (1 mg/kg, intraportal) was similar. Simultaneous activation of hepatic sympathetic and parasympathetic nerves therefore produces a purely sympathetic type of effect on net glucose balance across the liver. It was also shown that changes in net splanchnic output or simply in arterial – hepatic venous glucose differences are an adequate reflection of liver glucose balance under the currently tested responses.
Blood pressure in conscious and anesthetized adrenal-enucleated Sprague–Dawley and Wistar–Furth rats
Authors: Hall C. E. , Nasseth D.
Published: April 2011

Systolic blood pressure was measured weekly in conscious and in anesthetized female Sprague–Dawley (SD) and Wistar–Furth (W/Fu) rats following adrenal enucleation, unilateral nephrectomy, and the imposition of a high salt intake. SD rats quickly developed adrenal-regeneration hypertension (ARH) which progressed rapidly, and was identifiable in both the conscious and the anesthetized state. W/Fu rats slowly developed mild ARH, which, with a single exception, was identifiable only in conscious animals; the arterial pressures were within the normotensive range under anesthesia. The depressor effect of ether was also greater in adrenal-enucleated W/Fu than in similarly prepared SD rats, and in hypertensives than in normotensives. It is concluded that blood pressure measurements taken under anesthesia may not be representative of the true resting blood pressures: this is likely to be a particularly crucial problem in identifying early hypertension under circumstances and in rat strains highly susceptible to the depressor effects of ether.
Measurement of diurnal core temperatures of rats in operant cages by AM telemetry
Authors: Thornhill J. A. , Hirst M. , Gowdey C. W.
Published: April 2011

A special AM telemetric system of recording core temperature was developed for rats working in individual, adjacent operant conditioning chambers within a sound-attenuated room. The system monitored core temperatures of each rat continuously and recorded them, in degrees Celsius, every 30 min so that diurnal patterns and fluctuations after saline or drug injections could be determined. Periodic comparisons showed close agreement with temperatures recorded by a rectal probe
Alterations in brain dopamine and serotonin metabolism during the development of tolerance to human β-endorphin in rats
Authors: Loon Glen R. Van , Souza Errol B. De , Kim Chul
Published: April 2011

Repeated intracisternal injections of human β-endorphin lead to development of tolerance with respect to the catalepsy, analgesia, and hypothermia which are seen following a single injection. The initial injection of β-endorphin results in increases in the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in neostriatum, as well as increases in the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in hypothalamus and brainstem and a decrease in 5-HIAA in hippocampus. In the present study, we report changes in metabolism of dopamine and serotonin in specific brain areas during the development of tolerance to β-endorphin. Thus, the development of tolerance to β-endorphin with respect to catalepsy, analgesia, and hypothermia may be mediated by development of tolerance to the effects of β-endorphin on brain dopamine and serotonin release.
Elevated vascular reactivity in the timolol-treated spontaneously hypertensive rat
Authors: Goldberg Mark T. , Triggle Christopher R.
Published: April 2011

Spontaneously hypertensive rats (SHR) treated in utero with a low dose, and from weaning with 6 mg/kg per day of oral timolol, a noncardioselective β-adrenergic blocker, did not develop hypertension. Isolated aortic rings from these animals showed increased reactivity to raised extracellular K+, when compared with tissues from timolol-treated Kyoto-Wistar (WKY) control rats. The normotensive SHR aorta also showed significant responsiveness to H+ and to high Ca2+ concentrations without previously depolarizing the tissue with high K+ These observations suggest that the increased reactivity seen in vascular smooth muscle from this animal does not develop secondary to elevated peripheral resistance and subsequent hypertrophy, and that the initiation of hypertension in this animal may be related to a membrane defect and (or) cellular defect which results in a facilitation of Ca2+ availability for the contractile proteins of the SHR vascular smooth muscle cell.
Permeability effects of the E2 prostaglandins on canine gastric mucosa
Authors: Bolton John P. , Cohen Max M.
Published: April 2011

The effects on gastric mucosal permeability (GMP) of the topical application and intravenous administration of prostaglandin E2 (PGE2), 15(S)-15-methyl prostaglandin E2 (15M), and 16,16-dimethyl prostaglandin E2 (16DM) were measured in canine Heidenhain pouches. Two groups of four dogs were used and each experiment consisted of a 3-h perfusion with an acid saline solution containing polyethylene glycol as a volume marker. The prostaglandin was either added to the perfusate or given by constant intravenous infusion. The H+ and Na+ fluxes were used to assess GMP. Topical (1–10 μg/mL) and intravenous (0.3–1.2 μg kg−1 h−1) 16DM increased the apparent Na+ flux into the pouch in association with the secretion of fluid by the pouches, but did not alter H+ flux. The PGE2 applied topically (10–1000 μg/mL) had a similar effect, but intravenously (0.3–1.2 mg kg−1 h−1) reduced the volume of pouch secretion and the apparent Na+ flux into the pouch without altering H+ flux. The 15M given in the same concentration as 16DM was without a consistent effect on ionic flux or volume of secretion. The E2 prostaglandins have no effect on normal GMP.
Interaction of ethanol and catecholamines on rat brain (Na+ + K+)-ATPase
Authors: Rangaraj N. , Kalant H.
Published: April 2011

The (Na+ + K+)-ATPase activity in rat brain homogenates was stimulated by either d(+)- or l(−)-noradrenaline (NA) or by dopamine (DA) when vanadium-contaminated ATP was used as substrate, but not with vanadium-free ATP. Addition of 6.25–50 mM ethanol (EtOH) alone had no effect on the activity of dilute (1:2600) homogenates; however, in the presence of l-NA or DA, but not of d-NA, it produced a concentration-dependent reduction of activity below control values, regardless of which ATP was used. The minimum concentrations of catecholamine producing sensitization of ATPase to EtOH were 10−12 M l-NA and 10−7 M DA. With concentrated (1:65 or 1:78) homogenates, EtOH produced concentration-dependent inhibition without addition of exogenous catecholamines. The inhibition of ATPase by EtOH in the concentrated homogenate was decreased by elevation of K+ concentration, and was prevented in both dilute and concentrated homogenates by phentolamine but not by propranolol. The findings suggest that the action of NA or an α receptor may alter the enzyme microenvironment, by an as yet unknown mechanism, rendering it more susceptible to inhibition by EtOH.
γ-Aminobutyric acid and primary afferent depolarization in feline spinal cord
Authors: Sastry B. R.
Published: April 2011

The effects of iontophoretically applied γ-aminobutyric acid (GABA), (−)-nipecotic acid (NCA), 2,4-diaminobutyric acid (DABA), and pentobarbital were examined on the thresholds for antidromic activation of single group I muscle afferents, in decerebrated spinal cats. GABA decreased the threshold for antidromic activation of the majority of the afferents. During this decrease in the threshold, the preterminal axons were depolarized. This depolarization was decreased by a prior depolarization, but increased by a hyperpolarization, of the afferent. During the depolarization of the afferent produced by GABA, the size of the orthodromic action potential was decreased. Iontophoretically applied bicuculline antagonized the effect of GABA on the threshold for antidromic activation of the afferents. NCA, DABA, and pentobarbital potentiated the action of GABA on the afferent terminal excitability. Pre-treatment of the animals with semicarbazide, which reportedly depletes spinal GABA, resulted in a reduction in the threshold produced by a conditioning stimulation of other group I afferents. GABA decreased the threshold for antidromic activation of the nonterminal regions of the afferents when applied near the stimulation sites. The amounts of GABA required to produce a decrease in the threshold of the nonterminal afferents were greater than those required to produce a comparable effect on the terminal regions of the fibres. Iontophoretically applied NCA and bicuculline, in amounts that were adequate to alter the effects of applied GABA, failed to affect the nerve stimulation-induced decrease in the threshold for antidromic activation of the fibres. Intravenously injected bicuculline, however, antagonized the actions of GABA as well as of the reduction in the threshold produced by nerve stimulation.These results indicate that (1) GABA-induced increase in the excitability of group I afferent terminals is associated with a depolarization of the afferent, (2) the uptake of iontophoretically applied amino acid into the spinal cord tissue appears to limit its action on the afferent terminal excitability, (3) GABA has a preterminal depolarizing action on group I muscle afferents, and (4) primary afferent depolarization produced by nerve stimulation may be of diffuse origin and, hence, cannot be significantly affected by iontophoretically applied NCA and bicuculline.
Lack of effect of chronic renal denervation on altered sodium reabsorption during increased ureteral pressure
Authors: Wilson D. R. , Cusimano M. , Honrath U.
Published: April 2011

The role of the renal nerves in the altered sodium reabsorption which occurs during increased ureteral pressure was studied using clearance techniques in anaesthetized rats undergoing diuresis induced by isotonic saline infusion. In rats with a sham denervated kidney, an ipsilateral increase in ureteral pressure to 20 cm H2O resulted in a marked and significant decrease in sodium and water excretion, increased fractional sodium reabsorption, and increased urine osmolality with no significant change in glomerular filtration rate. A similar significant ipsilateral increase in tubular reabsorption of sodium occurred in rats with chronically denervated kidneys during increased ureteral pressure. The changes in tubular reabsorption were rapidly reversible after return of ureteral pressure to normal. These experiments indicate that enhanced tubular reabsorption of sodium during an ipsilateral increase in ureteral pressure is not mediated by increased renal nerve activity. During the antinatriuresis of increased ureteral pressure there was a decrease in the fractional reabsorption of sodium from the opposite normal kidney. The role of the renal nerves in this compensatory change in function in the opposite kidney was studied in two further groups of animals. The renal response to a contralateral increase in ureteral pressure was similar in denervated and sham-denervated kidneys. The results indicate that altered renal nerve activity, through ipsilateral or contralateral renorenal reflexes, is not responsible for the changes in tubular reabsorption of sodium which occur during increased ureteral pressure induced by partial ureteral obstruction.
Effects of oral perhexiline on canine myocardial flow distribution
Authors: Klassen Gerald A. , Zborowska-Sluis Danuta T. , Wright George J.
Published: April 2011

Perhexiline maleate at a dose of 400 mg three times daily for 2 days administered to normal dogs altered the relative regional transmural resistance so that during reduced coronary flow the endocardium:epicardium (endo:epi) ratio is increased. In the presence of acute myocardial infarction heart rate was significantly lower and the endo:epi ratio of perfused areas was increased when coronary flow was normal. A linear relationship was observed between the endo:epi ratio and the concentration of perhexiline in plasma, and its monohydroxyl metabolite in plasma. The results suggest that the mechanism of action of the drug is due to redistribution of a limited coronary flow.
Myocardial effects and pharmacokinetics of digoxin and ouabain in protein-deficient guinea pigs
Authors: Varma D. R.
Published: April 2011

Myocardial effects and pharmacokinetics of digoxin and ouabain were studied in male albino guinea pigs fed ad libitum either a 21% (control) or a 5% (low) protein diet for 4 weeks. Dietary protein deficiency was associated with a decrease in body weight gain, ventricular weight, total plasma proteins and plasma albumin, hepatic total and microsomal proteins, cytochrome P-450, and protein:DNA ratios; serum potassium was slightly but insignificantly decreased. No significant differences were found in the following experiments with digoxin and ouabain in control and protein-deficient animals: inotropic effects of ouabain on isolated papillary muscles and left atria; uptake of [3H]ouabain by isolated papillary muscles; ventricular fibriliatory doses of digoxin and ouabain in anesthetized animals and the concentrations of digoxin in plasma and papillary muscles at the onset of ventricular fibrillation in these animals; plasma half-life of digoxin in unanesthetized guinea pigs. It is concluded that although dietary protein deficiency influences several physiological and biochemical parameters it does not alter the myocardial effects and pharmacokinetics of digoxin and ouabain in guinea pigs.
Direct effects of estrogens on the endocrine function of the mammalian testis
Authors: Moger W. H.
Published: April 2011

This article reviews literature relevant to the view that estradiol (E2) synthesized in the testis acts locally to modify testosterone secretion. Despite a lack of convincing evidence from in vitro experiments, in vivo experiments with intact and hypophysectomized animals have demonstrated that estrogens can inhibit testosterone secretion by acting directly on the testis. Reduced testosterone production in estrogen-treated animals probably results from reduced 17α-hydroxylase and (or) C17–C20 lyase activity. Estrogen-inhibited steroidogenesis may result from estrogen binding to high affinity – low capacity estrogen receptors. Besides being an estrogen target tissue, the testis produces E2; the cellular site of testicular E2 synthesis remains controversial. Recent studies indicate that E2 is synthesized primarily in the Sertoli cells of neonatal rats and in the Leydig cells of older rats. Follicle-stimulating hormone and human chorionic gonadotropin (hCG) increase testicular aromatase activity and E2 concentrations in neonatal and older rats, respectively. An increase in testicular E2 concentrations, following hCG administration, may be one mechanism by which testosterone synthesis becomes desensitized to subsequent hCG stimulation. However, whether gonadotropin-stimulated testicular E2 synthesis is part of a physiologically relevant "short" feedback loop that participates in the regulation of testosterone synthesis remains to be determined.
Uptake and distribution of halothane in dog blood
Authors: Pang Y. C. , Reid P. E. , Brooks D. E. , Leighton K. M. , Bruce C.
Published: April 2011

The uptake and distribution of halothane in dog blood were studied by analysing the whole blood and plasma concentrations of halothane in samples of arterial and mixed venous blood at different times after the induction of anesthesia with constant inspired halothane levels of 1.0, 1.5, 2.0, and 2.5%, respectively. In general a steady state was reached 2–3 h after induction. Comparison of the arterial blood concentration calculated from end-tidal halothane partial pressure with that determined by direct analysis of the blood indicated that halothane in the alveoli and halothane in arterial blood are not in thermodynamic equilibrium. The arterial halothane concentrations calculated from the end-tidal halothane partial pressure assuming equilibrium is much higher than those found experimentally; thus end-tidal halothane partial pressure is not a true measure of blood halothane concentration. The distribution of halothane between the plasma and cells in blood appeared to be sufficiently rapid to be independent of the approach to the steady state.
Use of the common carotid artery in blood pressure measurement in rats. A possible source of error
Authors: Pang S. C. , Scott T. M.
Published: April 2011

Comparison of blood pressures obtained by femoral and common carotid artery cannulation has shown that in the rat anaesthetized with Nembutal an increase in blood pressure occurs after neck surgery and common carotid artery cannulation.
Two distinct inhibitory responses of cultured, mammalian spinal neurones to ibotenic acid
Authors: MacDonald John Ferguson , Barker Jeffery L.
Published: April 2011

Ibotenic acid, a structural analogue of glutamic acid, was applied to mouse spinal neurones grown in dissociated cultures. This amino acid evoked two inhibitory responses in addition to an excitatory response. Both inhibitory responses were manifested by membrane hyperpolarization and decreased input resistance. However, one was long-lasting (in excess of periods of 1 h) in comparison with the other. The latter response was likely a consequence of an increased chloride conductance and was sensitive to the γ-aminobutyric acid antagonists bicuculline and picrotoxin whereas the former response was insensitive to these drugs. The ionic mechanism of this long-lasting response has yet to be elucidated.
Effects of amphotericin B on the electrical properties and electrolyte content of frog sartorius muscle
Authors: Coulombe A. , Schanne O. F. , Reisin I. , Ruiz-Ceretti E.
Published: April 2011

We studied the effect of amphotericin B (52 μM) on the membrane potential, membrane resistance, and intracellular Na+ and K+ concentrations in isolated frog sartorius muscles to characterize further the nature of the ionic conductance induced by the antibiotic. After 5 h of exposure to amphotericin B, the membrane depolarized from −89.9 to −51.0 mV, the membrane resistance decreased from 4537 to 907 Ωcm2, [K]i decreased from 122 to 31.2 mmol/L fiber H2O, and [Na]i increased from 30.9 to 88.7 mmol/L fiber H2O. The relative sodium permeability, PNa/PK, calculated with the Goldman equation remained apparently constant at a value of 0.01 in treated and untreated muscles. We hypothesize that amphotericin B creates either a nonselective cation channel or a completely nonselective ionic leak channel whose equilibrium potential is equal or close to the membrane potential.
Effects of bradykinin on intestinal transcapillary fluid exchange
Authors: Barrowman J. A. , Perry M. A. , Kvietys P. R. , Ulrich M. , Granger D. N.
Published: April 2011

Bradykinin (50 μg∙L−1) increases intestinal lymph flow sixfold when infused intraarterially into the cat ileum. The capillary filtration coefficient and capillary pressure increase and interstitial fluid pressure rises from negative to positive values. A slight increase in lymph:plasma protein concentration occurs with a resulting fall in the transcapillary oncotic pressure gradient. These results indicate that the effect of bradykinin on intestinal lymph flow is attributable, at least in part, to increased capillary pressure, exchange vessel surface area, and a reduction in the effective transcapillary oncotic pressure gradient.