bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical coupling in the circular muscles of dog jejunum
Authors: Zelcer Elane , Daniel E. E.
Published: April 2011

Two distinct layers of circular muscle have previously been demonstrated in dog jejunum, the main circular layer containing many gap junction contacts, and an inner dense muscle layer where no gap junctions have been found. Length constants were determined for these muscle layers and no significant difference was found between these values. The main circular muscle cells had lower membrane potentials and may have had abnormally low space constants owing to injury. It was concluded that the absence of gap junctions in the inner dense layer does not reduce the spread of passive current as might be expected of electrically isolated cells, and it is suggested that an alternate pathway for passive current exists in this layer.
Effect of testosterone and 6-hydroxydopamine treatment on the metabolism of catecholamine and 5-hydroxytryptamine in methylcholanthrene-induced prostate carcinoma of rats
Authors: Rastogi R. B. , Agarwal I. R. A. , Jande S. S. , Singhal R. L.
Published: April 2011

The precursors tyrosine and tryptophan as well as the synthesizing and deaminating enzymes of catecholamines have been identified in methylcholanthrene-induced prostatic carcinoma of rats. Tyrosine hydroxylase, monoamine oxidase, catechol O-methyltransferase, dopamine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid seemed to be neoplastic in origin, since electron microscopic studies failed to reveal the presence of any neuronal elements in this squamous epithelial cell carcinoma. Castration of rats significantly reduced the activity of tyrosine hydroxylase and the levels of tyrosine, dopamine, tryptophan, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid in prostate tumors. The changes appeared to be androgen specific since reintroduction of testosterone restored several of these biochemical parameters virtually to control limits. Chemical sympathectomy induced by 6-hydroxydopamine failed to alter monoamine metabolism; however, the prostatic tumor grown in 6-hydroxydopamine-treated rats showed significantly (32%) less necrosis than those grown in normal animals.
Central antihypertensive properties of muscimol and related γ-aminobutyric acid agonists and the interaction of muscimol with baroreceptor reflexes
Authors: Sweet Charles S. , Wenger Herbert C. , Gross Dennis M.
Published: April 2011

The central antihypertensive properties of four γ-aminobutyric acid (GABA) analogs were characterized in anesthetized cats with implanted intracerebroventricular cannulae. An intracerebroventricular infusion (icv) of muscimol, 0.1–0.5 μg/min (total dose: 1–5 μg, icv), substantially reduced mean arterial pressure and slightly reduced heart rate. The compound was not hypotensive at 5 μg, iv (total dose) and only slightly hypotensive after an intracisternal injection (5 μg). Kojic amine (2-aminomethyl-5-hydroxy-4H-pyran-4-one) and baclofen were also hypotensive following an intracerebroventricular infusion, but they were less active than muscimol. GABA, at 15–150 μg/min, icv (total dose, 150–1500 μg, icv), was not hypotensive by itself and unlike muscimol its activity was not enhanced in cats pretreated with nipecotic acid, an uptake inhibitor of GABA. The ability of muscimol to interfere with baroreceptor reflexes was considered in experiments in which reflex vasoconstrictor (carotid occlusion) and reflex vasodilatation (acute elevation in mean arterial pressure with norepinephrine) was measured in the perfused hindlimb of cats previously prepared with intracerebroventricular cannulae. Muscimol significantly attenuated the response to bilateral carotid occlusion and completely abolished reflex vasodilatation. These results suggest that GABA agonists and analogs may regulate blood pressure centrally and, through an interaction with the central nervous system, may attenuate baroreceptor reflexes.
Alterations in ventilation and gas exchange during exercise-induced carbohydrate depletion
Authors: Green H. , Houston M. , Thomson J. , Reid P.
Published: April 2011

The relationships between ventilation [Formula: see text], oxygen consumption [Formula: see text], and carbon dioxide production [Formula: see text] during work were studied in four trained males during exercise-induced carbohydrate depletion. Repeated bouts of heavy treadmill exercise (6 min at 95% [Formula: see text]max) were performed once per hour for 24 h in order to promote a shift in energy substrate from carbohydrate to fat. Measurements of [Formula: see text] and [Formula: see text] recorded during each minute indicated that [Formula: see text] was unaffected by the number of runs, whereas [Formula: see text] showed a progressive reduction which amounted to 24% during the final run. A corresponding decline of 19% was observed in the respiratory exchange ratio. No significant change in [Formula: see text] occurred between any of the runs. It is concluded that during heavy, repeated, muscular exercise, reductions in [Formula: see text], strongly suggestive of an increased fat oxidation, are not accompanied by a corresponding change in ventilation.
Neck muscle and trigeminal input to the upper cervical cord and lower medulla of the cat
Authors: Abrahams V. C. , Anstee G. , Richmond F. J. R. , Rose P. K.
Published: April 2011

Experiments on chloralose-anaesthetized cats have shown that low-threshold neck muscle afferents project to laminae IV and V in the dorsal horn of the upper cervical cord, to lamina VI including the region which encompasses the central cervical nucleus, as well as to extensive regions of the ventral horn. At posterior medullary levels projections also exist to laminae IV, V, and VI of the spinal nucleus of V (although those to lamina IV are circumscribed), to the deep layers and lateral margin of the cuneate nucleus, and to the inferior olive. These projections are both from low- and high-threshold afferents. Evidence of a functional relationship between the trigeminal and neck muscle afferent system was found both in the upper cervical cord and lower medulla. About 40% of units in both regions receive a convergent input and when convergence could not be demonstrated, prior stimulation of one modality in some instances affected the responsiveness of the unit to the other modality. A motor role was found for some trigeminal afferent projections to the upper cervical cord. Trigeminal afferents consistently activated antidromically identified motoneurons of splenius, biventer cervicis, and complexus.
Correction of end-plate potentials and currents for nonlinear summation
Authors: Quastel D. M. J.
Published: April 2011

When transmitter substance acts to increase ionic conductance of a subsynaptic membrane, the resulting potential change is not linearly related to the conductance change. Peak potential changes (v) were computed for an equivalent circuit corresponding to the neuromuscular junction: the postsynaptic cell was simulated as a 'cable' with distributed capacitance and the conductance change was made to fall exponentially from an initial peak. For this model it was found that the quantity v/(1 − vE−1 a−1) is very nearly proportional to peak synaptic conductance, where E is the difference between synaptic equilibrium potential and membrane potential, and a is close to unity. That is, Martin's relation remains applicable even when the synaptic conductance is brief. The same equation holds, but with reduced a, when recording is nonfocal and (or) when the rate of decline of the synaptic conductance change is increased by the change of potential that it induces. Therefore, exact correction of end-plate potentials for nonlinearity is not possible. However, for recording that is close to focal and v/E less than 20%, there should be little error in the above 'correction' using a = 1 − 0.00135E, where E is expressed in millivolts. In the case of a 'point' voltage clamp, the recorded current is equal to the synaptic current only if the clamping electrodes are placed exactly focally, which may be technically impossible. Otherwise, the relation between recorded current and conductance is similar to that between v and conductance: nonlinearity may be quite large even when a clamp is very nearly focal, when synaptic conductance is large.
Age-dependent changes in the response of the lamb ductus arteriosus to oxygen and ibuprofen
Authors: Coceani F. , White E. , Bodach E. , Olley P. M.
Published: April 2011

Circular strips of ductus arteriosus from lambs of gestational age between 90 and 144 days (term 147 days) were studied in vitro at low (8–16 torr (1 torr = 133.322 Pa)) and high (426–622 torr) [Formula: see text]. Potassium- and oxygen-induced contractions increased with the gestational age and attained a maximum at term. At low [Formula: see text], ibuprofen, a blocker of prostaglandin synthesis, produced a dose-dependent contraction of the ductus at all ages and enhanced the potassium-induced contraction of the immature ductus (90–124 days). Both effects were relatively greater in the 103- to 107-day gestational group. At that age, ibuprofen also potentiated the oxygen-induced contraction. These findings, while confirming that a prostaglandin is involved in ductus patency, indicate that the prostaglandin-relaxing mechanism becomes functional at an early stage of gestation and reaches maximal activity before term. The existence of an active, prostaglandin-mediated relaxation in the preterm ductus may account, in part, for the reduced responsiveness of the vessel to oxygen. It is confirmed that ibuprofen and other nonsteroidal antiinflammatory drugs are well suited for the management of the premature infant with patent ductus arteriosus.
Failure to reverse cholera toxin induced intestinal secretion by agents which decrease mucosal cAMP
Authors: Forsyth G. W. , Hamilton D. L. , Scoot A. , Goertz K. E. , Kapitany R. A.
Published: April 2011

The feasibility of reducing intestinal secretion by the use of agents which decrease intestinal mucosal cAMP concentration has been investigated in the weanling pig and the rabbit. Three different agents for decreasing mucosal cAMP concentration were studied. The cyclic nucleotide phosphodiesterase activator, imidazole, significantly reduced mucosal cAMP concentrations only in the weanling pig. Intraluminal 2′-deoxyadenosine-3′-AMP inhibited adenylate cyclase and caused a decrease in mucosal cAMP concentration in both the pig and the rabbit. The introduction of the heat-stable enterotoxin of Escherichia coli into pig jejunal segments also gave lowered mucosal cAMP concentrations. While these three agents effectively reduced cAMP concentrations in intestinal mucosa, they were ineffective in reducing the net fluid secretory effects of cholera toxin. Secretion caused by cholera toxin apparently persists independent of the temporary changes in cAMP concentration which can be induced by pharmacological agents.
Brain benzodiazepine levels following intravenous administration of [3H]diazepam: Relationship to the potentiation of purinergic depression of central nervous system neurons
Authors: Skolnick Phil , Paul Steven M. , Marangos Paul J.
Published: April 2011

Levels of [3H] benzodiazepine were measured in rat cerebral cortex following intravenous injection of [3H]diazepam using a dose and time schedule reported to elicit a marked potentiation of the depressant effects of iontophoretically applied 5′-AMP to rat cerebral cortical neurons. The levels of [3H]benzodiazepine obtained strongly suggest (i) that blockade of adenosine uptake as a mechanism for this potentiation is not consistent with the potency of diazepam as an inhibitor of adenosine uptake in vitro, and (ii) that a potentiative interaction of adenosine and diazepam may reflect the binding of these compounds to benzodiazepine receptors.
The reliability of rates of glucose appearance in vivo calculated from single tracer injections
Authors: Allsop John R. , Wolfe Robert R. , DiStephano III Joseph J. , Burke John F.
Published: April 2011

The rate of appearance of unlabelled glucose was calculated from changes in plasma glucose specific radioactivity after a single intravenous injection of labelled glucose and compared with the actual constant infusion rate of unlabelled glucose into an anaesthetized dog with all sources of endogenous glucose production surgically removed. The mean steady-state rate of appearance of unlabelled glucose calculated from the area under the specific radioactivity versus time curve was 7% higher than the actual infusion rate (n = 4), but the difference was not statistically significant. The variability in the rate calculated in this manner was, however, greater than the variability we have reported with rates determined from a primed constant infusion of tracer. Using 15- to 60- or 60- to 120-min specific radioactivity data the mean rate of appearance of glucose, calculated on the assumption of a one-pool model for glucose turnover in vivo, was approximately 60% higher than the actual infusion rate. The results also indicate that it is possible to construct multi-pool models, but it is difficult to equate specific physiological events with the individual terms of the multi-exponential equation which describes the changes in plasma glucose specific radioactivity.
Separate hypoglycaemic thresholds for gastric acid and pepsin secretion following insulin or posterior hypothalamic stimulation
Authors: Webber D. E. , Morrissey Shelagh M.
Published: April 2011

The level of hypoglycaemia required to elicit gastric secretion of acid and pepsin was studied in urethane-anaesthetized rats. Hypoglycaemia was induced by intravenous injection of insulin or by electrical stimulation of the posterior hypothalamus. In each case the blood glucose values below which gastric secretion was stimulated were significantly higher for pepsin than for acid secretion. This consistently resulted in the onset of pepsin secretion in advance of the onset of acid secretion. These observations suggest that the production of the different components of the gastric juice was under the influence of either separate hypothalamic glucoreceptors, or a single set of glucoreceptors able to respond selectively to different blood glucose levels.
The effects of prolonged chilling upon in vitro Ca2+ accumulation, influx, and growth hormone release in rat adenohypophysis
Authors: Milligan John V. , Kraicer Jacob
Published: April 2011

The exposure of rat adenohypophysial tissue to iced media for periods of 30–60 min causes accumulation of Ca2+ by the tissue and an increased "basal" release of growth hormone into the media. The Ca2+ permeability following the chill, estimated from the uptake of 45Ca2+ by the tissue at 37 °C, is unchanged by the exposure to iced media. This suggests that the accumulation of Ca2+, which occurs during the chill, may be due simply to decreased efflux of Ca2+. The insensitivity of 45Ca2+ influx to the increased cellular content is readily explained if Ca2+ is rapidly sequestered after it has entered the cell. Our previous investigations snowed an increase in 45Ca2+ uptake (permeability) associated with hormone release which had been induced by elevated K+ or by partially purified releasing factor. We used tissue that had been chilled during collection. Our studies here indicate that our previous observations of increased uptake are qualitatively correct despite the cellular accumulation of Ca2+ that must have occurred before exposure to the secretagogues. The release of hormone seems to be related to the absolute cytoplasmic concentration of Ca2+ and release will occur in any circumstance that increases this concentration. The source of Ca2+ is not critical.
Effects of phentolamine on thermoregulatory functions of rats to different ambient temperatures
Authors: Lin M. T. , Chandra Andi , Fung T. C.
Published: April 2011

The effects of both systemic and central administration of phentolamine on the thermoregulatory functions of conscious rats to various ambient temperatures were assessed. Injection of phentolamine intraperitoneally or into a lateral cerebral ventricle both produced a dose-dependent fall in rectal temperature at room temperature and below it. At a cold environmental temperature (8 °C) the hypothermia in response to phentolamine was due to a decrease in metabolic heat production, but at room temperature (22 °C) the hypothermia was due to cutaneous vasodilatation (as indicated by an increase in foot and tail skin temperatures) and decreased metabolic heat production. There were no changes in respiratory evaporative heat loss. However, in the hot environment (30 °C), phentolamine administration produced no changes in rectal temperature or other thermoregulatory responses. A central component of action is indicated by the fact that a much smaller intraventricular dose of phentolamine was required to exert the same effect as intraperitoneal injection. The data indicate that phentolamine decreases heat production and (or) increases heat loss which leads to hypothermia, probably via central nervous system actions.
Changes in subcellular membranes in rat heart perfused with diethyl ether
Authors: Taam Gina M. L. , Takeo Satoshi , Panagia Vincenzo , Ziegelhoffer Attila , Dhalla Naranjan S.
Published: April 2011

Alterations in contractile force as well as heart sarcolemmal, microsomal, and mitochondrial activities were investigated by perfusing rat hearts with different concentrations (0.5–1.5% (v/v)) of ether for 2 min. Contractile force of the perfused heart was depressed by 0.5–1.0% ether and completely abolished by 1.25–1.5% ether. The contractile force recovered fully upon reperfusion when the hearts were preperfused with 0.5–0.75% ether but the recovery was partial in hearts preperfused with 1.0–1.25% ether. The hearts preperfused with 1.5% ether did not recover their ability to generate contractile force upon reperfusion. The Na+–K+-ATPase activity of sarcolemma obtained from hearts perfused with 0.75–1.0% ether was higher than the control value. The sarcolemmal Na+–K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, calcium binding, and adenylate cyclase activities were decreased in hearts perfused with 1.5% ether and these activities were further decreased upon reperfusion. The microsomal calcium binding and uptake activities were depressed in hearts perfused with 1.0–1.5% ether and these changes were irreversible. The mitochondrial calcium binding and uptake activities as well as oxidative phosphorylation activity were also depressed in hearts perfused with 1.0–1.5% ether; however, irreversible damage was seen in hearts perfused with 1.5% ether. Electron microscopic examination showed occasional vacuolization of mitochondria in hearts perfused with 1% ether and swelling of sarcoplasmic reticulum and mitochondria as well as damage to myofilaments were seen in hearts perfused with 1.5% ether. These results suggest the involvement of alterations in subcellular membrane system in the cardiotoxic actions of ether.
Endogenous pyrogen release by fetal sheep and pregnant sheep blood leukocytes
Authors: Kasting N. W. , Veale W. L. , Cooper K. E.
Published: April 2011

These experiments were undertaken to determine if fetal blood leukocytes are capable of producing endogenous pyrogen (EP), as neither the fetal nor newborn lamb can produce a fever in response to bacterial endotoxin. Maternal leukocytes were also tested for their ability to produce EP as the near-term pregnant sheep cannot produce a fever in response to bacterial endotoxins or EP. The results demonstrate that both fetal and near-term maternal leukocytes can produce EP, thus supporting experimental evidence that the inability of the newborn and near-term mother to become febrile is due to a process other than lack of EP production.
Stereospecific augmentation of hippocampal pyramidal cell responses by morphine is dependent on their position on the input–output curve
Authors: Corrigall W. A. , Linseman M. A.
Published: April 2011

The effect of morphine (0.5–50 μM) was examined on CA1 field potentials in the transverse hippocampal slice. Morphine consistently produced an augmentation of orthodromic evoked activity in stratum pyramidale (population spike) manifest as (i) a shift to lower threshold of the entire input–output curve for the neurons which was naloxone reversible near threshold only, and (ii) generation of an additional population spike whose amplitude was proportional to the position of the sampled response on its input–output curve, and which was fully naloxone reversible. Both effects were stereospecific. The phenomena were not accompanied by simultaneous changes in potentials in the dendritic regions (population excitatory postsynaptic potential) of CA1, and only the second effect was observed during antidromic activation of the pyramidal cells. The results indicate the importance of assessing full input–output characteristics of drug effects.
The actions of praziquantel and 1-methyladenine in guinea pig ileal longitudinal muscle
Authors: Jim K. , Triggle D. J.
Published: April 2011

Praziquantel (10−4 M) and 1-methyladenine (5 × 10−4 M) produced mechanical responses in guinea pig ileal longitudinal smooth muscle that were approximately 20% of those produced by muscarinic receptor stimulation. These responses were insensitive to tetrodotoxin and atropine but were dependent upon the extracellular concentration of Ca2+ and were abolished by D 600 at a concentration (10−6 M) which abolished the Ca2+-dependent muscarinic responses. Thus, praziquantel and 1-methyladenine may act as modulators of Ca2+ channel function in guinea pig ileal muscle.
Water content, water turnover, and water half-life during cold acclimation in the rhesus monkey
Authors: Oddershede IB R. , Elizondo Reynaldo S.
Published: April 2011

The purpose of this study was to examine the effects of cold acclimation on the dynamics of body water in primates. Six male rhesus monkeys were acclimated for 35 days at 6 °C. Water turnover rate (WTR), biological half-life (t1/23H2O), and total body water (TBW) were estimated by the tritium dilution method. A reduced water intake during the 1st week of cold acclimation was associated with a decrease in water balance (total water input minus WTR). Both drinking and total water input were decreased throughout the cold exposure. WTR was significantly decreased during the last 3 weeks of cold exposure in spite of an increased caloric consumption, which, in a thermoneutral environment, generally is associated with an increased WTR. Biological half-life for tritium showed a significant average increase during the cold stress. TBW in relation to body weight was increased during the first 2 weeks of cold exposure and had decreased to its lowest level by day 22. Calculations of TBW were independent of whether the radioactive decay curve was obtained over short (minutes) or long (days) time intervals and independent of the degree of acclimation. The major adjustments in water content and water metabolism occurred within 2 weeks of continuous cold exposure at 6 °C. The data suggest that the rhesus monkey may be an adequate primate model for studies of body fluid adjustments induced by chronic cold exposure in primates in general, including man.
The effect of several α-adrenoceptor antagonists on the response to histamine in various tissues
Authors: MacLeod K. M. , Krueger C. A. , Smith D. , Iwanow D. M. , Cook D. A.
Published: April 2011

The effect of various α-receptor antagonists on the histamine-induced response of guinea pig ileum, guinea pig heart, and rabbit portal vein have been studied. In guinea pig ileum, an H1 receptor system, phenoxybenzamine and dibozane are effective antagonists, phentolamine is a weak antagonist, azapetine is without antagonist effect, and tolazoline is a weak agonist. In the H2 system of guinea pig right ventricle, phentolamine and azapetine are antagonists, phenoxybenzamine and dibozane are inactive, and tolazoline is an agonist. All antagonists except tolazoline block the histamine response in portal vein which is believed to be mediated by a receptor of low selectivity. Tolazoline is an agonist in portal vein.
The in vivo uptake of [3H]isoprenaline by the chick embryonic heart and liver
Authors: Oštádal B. , Babický A. , Kopoldová J.
Published: April 2011

Seven-day-old embryos received 3.7 × 105 Bq (10 μCi) of [3H]isoprenaline (IPRO) hydrochloride intraamnially. The capacity of myocardial and liver tissue for taking up administered catecholamine increased rapidly during the first 10 min after administration. The peak concentration (disintegrations per minute per milligram) in the heart, however, was significantly lower as compared with the liver. Thereafter the uptake in both organs markedly decreased and reached its lowest values between 15 and 30 min. From then on, the concentration of the tritium-labelled compound increased again and 6 h after administration it attained the second peak in both organs. This value was more than five times higher in the liver as compared with the myocardium.Radiometric evaluation of chromatograms from myocardial and liver extracts has revealed that IPRO is rapidly metabolized to 3-O-methyl IPRO. The proportion of this fraction in both organs represents approximately 40% of total radioactivity as early as 5 min after administration.The time course of IPRO uptake indicates that the following factors may participate in the development of cardiac and hepatic lesions: (a) IPRO immediately after administration, and (b) subsequently its toxic metabolites.
Elasticity of ligated carotid arteries of rabbits with and without a cholesterol-rich diet
Authors: Lim Koon Ong , Terpin Teresa , Roach Margot R.
Published: April 2011

Elasticity of carotid arterial segments of rabbits proximal and distal to an induced ligation was examined. In the presence of both ligation and hypercholesterolemia, longitudinal distensibility was decreased while circumferential distensibility increased. The decrease in longitudinal distensibility was attributed to a decrease in the slack of collagen while the increase in circumferential distensibility was attributed to an increase in the slack of collagen as well as a decrease in the elastances of elastin and collagen. Cholesterol alone was found not to affect the elasticity, while ligation acting alone slightly decreased the circumferential distensibility while leaving the longitudinal distensibility unchanged. High serum cholesterol was also found to accelerate intimal proliferation in regions near the ligature. Some intimal proliferation was seen near the ligature, but this could not be quantitated as the sections were too short for pressure fixation. If intimal proliferation is a precursor of atherosclerotic lesions, then formation of these lesions might be accelerated near occluded regions and maybe also in regions of disturbed blood flow when high serum cholesterol is present.
Absence of effect of somatostatin on the guinea pig gallbladder
Authors: Poitras Pierre , Yamada Tadataka , Walsh John H.
Published: April 2011

The effect of somatostatin (GH-RIH) on cholecystokinin octapeptide (OP-CCK) or acetylcholine (ACh) induced contraction of the guinea pig gallbladder was evaluated in vitro. GH-RIH failed to inhibit the muscle contraction induced by OP-CCK or ACh. To correlate with the in vitro results, the effect of GH-RIH on OP-CCK induced contraction of the gallbladder was evaluated in the guinea pig in vivo. GH-RIH did not affect the OP-CCK induced contraction of the gallbladder. Our results suggest that GH-RIH does not have direct inhibitory effect on the contraction of the guinea pig gallbladder induced by OP-CCK or ACh.
Prostaglandin E2 catabolism in the spinal nerve roots of the cat
Authors: Bishai I. , Coceani F.
Published: April 2011

Catabolism of prostaglandin (PG) E2 was studied in homogenates of spinal cord and spinal nerve roots of the cat. Spinal roots enzymatically converted PGE2 to a product (metabolite I) with the chromatographic mobility of 15-keto-PGE2. Little metabolic degradation occurred in the spinal cord; however, incubation of PGE2 with combined spinal cord and nerve root tissue yielded a second metabolite (metabolite II) in addition to metabolite I. Metabolite II was identified as 15-keto-13,14-dihydro-PGE2. These results prove that spinal nerve roots, unlike the spinal cord, contain 15-hydroxyprostaglandin dehydrogenase (15-PGDH) which is the major and rate-limiting enzyme in the inactivation of prostaglandins. The location and functional significance of 15-PGDH in peripheral nerves remain to be elucidated.
Observed differences in dextran and polyvinylpyrrolidone as rouleaux-inducing agents
Authors: Sewchand Lionel S. , Bruckschwaiger Dieter
Published: April 2011

The effectiveness of dextran fractions (Dx-500, Dx-100, Dx-70) and polyvinylpyrrolidone (PVP-360, PVP-40) in inducing aggregation of red blood cells (RBC) was studied in a nonflowing environment. The Dx fractions, at low concentrations, induced aggregation of human RBC but failed to do so at high concentrations (concentrations greater than 70 g/L). The effect was different on RBC from animal species (cat and rabbit); aggregation increased steadily with the Dx concentration and there was no critical concentration beyond which Dx failed to induce aggregation. The PVP was found to be very effective, at all concentrations, in inducing aggregation of RBC from both human and the animal species. These results have a twofold significance: (1) they suggest that Dx and PVP, both neutral polymers, interact differently with the human RBC membrane; and (2) the association of Dx with the human RBC membrane is different from that with cat and rabbit RBC membranes.
Enhanced vascular reactivity to various vasoconstrictor agents following pinealectomy in the rat: role of melatonin
Authors: Cunnane Stephen C. , Manku Mehar S. , Oka Masatsugu , Horrobin David F.
Published: April 2011

The mesenteric vascular bed preparation of control and pinealectomized (PX) male Wistar rats was used to examine vascular reactivity to two concentrations each of norepinephrine, serotonin, angiotensin, and potassium. Vasoconstrictor responses to 50- and 100-ng injections of norepinephrine and 0.5- and 1.0-μg injections of serotonin were 30–40% higher in preparations from PX rats. Responses to 100 ng but not to 50 ng of angiotensin were also significantly higher in preparations from PX rats. Responses to 1.5- and to 3.0-mg injections of potassium did not differ significantly in either case. In vivo injection of 20 μg of melatonin 3 h prior to dissection of the preparation, or in vitro perfusion of 20 ng melatonin per millilitre of buffer completely reversed the increased vascular response to all vasoconstrictor agents tested in the PX preparations, but had little effect in control preparations. Also observed in PX rats was a significant increase in blood pressure, serum sodium, and increased body and heart weight. Arterial wall sodium was also elevated in PX rats. These changes may be relevant to the increased vascular reactivity of PX rats. The increased vascular responsiveness of PX rats may be specific for agents that stimulate calcium release from intracellular stores (norepinephrine, angiotensin) rather than those that stimulate calcium influx from extracellular fluid (potassium). Melatonin lack may be the cause of the vascular changes in the PX rats as both in vivo and in vitro it lowered the vasoconstrictor effects of the agents tested, but only in PX rats; it had no significant effect in the control rats.
Effects of different opiate agonists on melanocyte-stimulating hormone release: in vivo and in vitro studies
Authors: Celis M. E.
Published: April 2011

The effects of Leu-enkephalin, Met-enkephalin, and β-endorphin on melanocyte-stimulating hormone (MSH) secretion were studied in vivo and in vitro. The three opioid peptides release MSH. In vitro this release is dose dependent for Met-enkephalin between 10 and 1000 ng/mL and for Leu-enkephalin between 10 and 100 ng/mL. β-Endorphin releases MSH at the low concentration of 1 ng/mL and the effect is dose dependent between 1 and 100 ng/mL. Naloxone reverses this effect. In vivo the three petptides release MSH.
Subcellular Ca2+ transport le different areas of dog heart
Authors: Dhalla N. S. , Sulakhe P. V. , Lee S. L. , Singal P. K. , Varley K. G. , Yates J. C.
Published: April 2011

Calcium transport and ATPase activities were determined in the heavy microsomal and mitochondrial fractions isolated from the left and right atria as well as ventricles of dogs. Ultrastructural distribution of these organelles in different areas of the myocardium was also examined. Calcium binding, calcium uptake, and calcium ATPase activities of the atrial microsomes were lower than those of the ventricles. On the other hand, mitochondrial calcium binding and uptake activities in the right atrium were higher than those in other areas. The mitochondrial total ATPase activities in the atria were also higher than those in the ventricles. Mitochondrial as well as microsomal yields from ventricles were significantly higher. Size and number of mitochondria in the ventricles were greater whereas no striking difference in the distribution of sarcoplasmic reticulum was apparent in different areas of the heart. Poorly developed calcium transport functions in the atrial microsomes may be one of the factors responsible for the generation of lower contractile force in this tissue in comparison with the ventricle.
Myocardial perfusion abnormalities in carbon monoxide poisoned dogs
Authors: Einzig Stanley , Nicoloff Demetre M. , Lucas Jr. Russell V.
Published: April 2011

The effect of carbon monoxide inhalation on the regional distribution of right and left ventricular myocardial blood flow was studied in 12 closed-chest anesthetized dogs. Dogs were exposed to a nonhypoxic mixture of oxygen (21–40%) and carbon monoxide (1.5–2.0%) for 10 min. Myocardial blood flow was measured (15-μm radionuclide-labeled spheres) during control conditions, and 10 and 60 min following discontinuation of carbon monoxide corresponding to carboxyhemoglobin levels (COHb) of 41.6 ± 2.8 and 26.5 ± 1.6% (mean ± SE), respectively. At a COHb level of 26.5%, right and left ventricular blood flows were increased to approximately 1.8–1.9 times the control values (1.06 ± 0.10 vs. 0.64 ± 0.08 mL/min per gram and 1.72 ± 0.12 vs. 0.91 ± 0.07 mL/min per gram, respectively, P < 0.002). At a COHb level of 41.6%, both right and left ventricular vascular beds were maximally or near maximally dilated as right ventricular and left ventricular myocardial blood flow values were increased approximately fivefold. The right and left ventricular subendocardial-subepicardial flow ratios were reduced at both COHb levels (P < 0.05). Thus, in addition to the global myocardial hypoxia that occurs following elevation of the COHb level, relative subendocardial underperfusion is a component of carbon monoxide poisoning in the intact dog.
The effects of ethanol on cerebellar Purkinje cells in naive and alcohol-dependent rats
Authors: Sinclair J. G. , Lo G. F. , Tien A. F.
Published: April 2011

In urethane-anaesthetized rats, ethanol (1.5 g/kg, i.v.) increased the rate of discharge of cerebellar Purkinje cells, increased their regularity of discharge, and reduced or eliminated the climbing fibre evoked bursts. Most of the neurones responding in this manner exhibited an acute tolerance to the drug. Another group of rats was made alcohol dependent by feeding them for 2 weeks on a diet containing ethanol (12.5–16.5 g/kg per day). Ethanol produced similar but reduced effects on Purkinje cells of these animals.
Influence of streptomycin on spontaneous activity of clusters of cultured cardiac cells from neonatal rats
Authors: Payet M. D. , Bkaily G. , Schanne O. F. , Ruiz-Ceretti E.
Published: April 2011

In clusters of trypsinized ventricle cells from neonatal rats which exhibit slow response action potentials, streptomycin in concentrations from 0.17 to 5.5 mM significantly inhibits the beating rate. Microelectrode experiments performed at a concentration of 5.5 mM revealed a reduction in the slope of diastolic depolarization from 149 to 53 mV/s whereas the maximum diastolic potential depolarized from −42.4 to −33.6 mV which entailed a decrease in overshoot and maximum rate of rise of the action potential. We conclude that the decrease of the slope of diastolic depolarization mainly determines the slowing of the beating rate and that streptomycin interferes with the pacemaker mechanism usually associated with the slow response.
β-Endorphin-induced prolactin secretion is mediated by suppression of release of newly synthesized hypothalamic dopamine
Authors: Loon Glen R. Van , Souza Errol B. De , Ho Doris , Shin S. H.
Published: April 2011

Intracisternal administration of synthetic human β-endorphin in rats increased plasma prolactin. This effect of β-endorphin is blocked completely by parenteral administration of the dopamine receptor agonist, apomorphine. Increasing availability of brain dopamine with the monoamine oxidase inhibitor, pargyline, blunted the effect of β-endorphin on plasma prolactin. Although the effect of apomorphine could have been mediated either in the hypothalamus or directly on pituitary, the action of pargyline could not have occurred in pituitary, thus providing support for the hypothesis that β-endorphin-induced prolactin secretion is mediated in brain and furthermore through a dopaminergic mechanism. Additional support for both aspects of this hypothesis is provided by the finding that decreasing availability of dopamine with the dopamine synthesis inhibitor, α-methyltyrosine, potentiated the effect of β-endorphin to increase plasma prolactin concentration.Furthermore, this potentiation by α-methyltyrosine of β-endorphin-induced prolactin secretion was evident at a time when mediobasal hypothalamic dopamine concentration had not yet decreased. Because the storage pool of dopamine does not appear to have been altered at this time, these data suggest that lack of newly synthesized hypothalamic dopamine potentiated the effect of β-endorphin to increase plasma prolactin. It seems probable that inhibition of release of newly synthesized (and preferentially released) tuberoinfundibular dopamine is important in mediating β-endorphin-induced prolactin secretion. Finally, intracisternal dexamethasone inhibited the synergistic effects of α-methyltyrosine and β-endorphin on prolactin secretion, perhaps by an action on hypothalamic aminergic neurons.
Microinjection of ouabain into crab single muscle fibers and the mechanism of ouabain potentiation
Authors: Fujino S. , Fujino M.
Published: April 2011

In order to clarify the mechanism of the potentiating effect of ouabain on contraction, a study was made of the effect of microinjection of 1.5 μL of ouabain on contractile responses and 22Na efflux, using single muscle fibers of crab (i–iii), and the results obtained were compared with observations (iv) on frog hearts. (i) Microinjected ouabain was dissolved with distilled water or isosmotic potassium glutamate solution. In both cases, ouabain remarkably potentiated both contraction evoked electrically and contractures induced by potassium or caffeine. (ii) Microinjected ouabain increased only the size of a contracture (water-induced contracture) which appeared immediately after the microinjection of distilled water into the fibers, reserpine increased only the duration of the contracture, and caffeine increased both the size and the duration of the contracture. (iii) In crab fibers equilibrated previously with 22Na-containing crab saline solution, extracellularly applied ouabain inhibited both contraction and 22Na efflux from the fibers whereas intracellularly applied ouabain markedly enhanced contraction without a change in the 22Na efflux, (iv) In frog hearts, extracellularly applied ouabain showed a positive inotropic action which was accompanied by occupation of a considerable cellular space by [3H]ouabain and not by a decrease in 22Na efflux. From these results, we concluded that for the appearance of ouabain potentiation the drug must get into the cell and that the potentiation was elicited independent of ouabain-induced inhibition of Na-K-ATPase activity in the muscle. Furthermore, a possible mechanism of the potentiating effect of ouabain on contraction was discussed.
Influence de l'administration aiguë ou chronique de l'éthanol sur la réponse pharmacologique à la méthaqualone
Authors: Rousseau Micheline , Rousseau Jean-Jacques , Brodeur Jules
Published: April 2011

This study was undertaken to investigate the influence of ethanol given either acutely or chronically on the pharmacological response to methaqualone. In order to define the mechanism(s) responsible for the interaction between ethanol and methaqualone, a study was also conducted on the influence of ethanol on microsomal activity, as well as on the disappearance curves of methaqualone in blood and brain. Although acute administration of ethanol (4 g/kg, orally) leads to a progressive inhibition of microsomal enzyme activity towards methaqualone, this is not accompanied by a prolongation of the sleeping time to the hypnotic. Under these conditions animals given both ethanol and methaqualone regain their righting reflex at higher brain concentrations of methaqualone than those given methaqualone only; this can be interpreted as being an acutely acquired tolerance phenomenon resulting from exposure to ethanol. Chronic ingestion (7 and 14 days) of 6% ethanol dissolved in an aqueous solution of 10% dextrose shortens the sleeping time to methaqualone provided the animals have access to ethanol until the administration of methaqualone. Once again, under these conditions, the concentrations of methaqualone in blood and brain at awakening are more elevated in pretreated animals than in control ones. These results suggest the development of a functional tolerance state as a result of ethanol pretreatment. Chronic ingestion of dextrose leads to inhibition of microsomal enzyme activity, yet this is not sufficient to prevent the appearance of a tolerance phenomenon.
Intracerebroventricular injection of sympathomimetic drugs inhibits both heat production and heat loss mechanisms in the rat
Authors: Lin M. T. , Chandra A. , Chern Y. F. , Tsay B. L.
Published: April 2011

The effects of intracerebroventricular (i.c.v.) injections of sympathomimetic drugs on thermoregulatory functions in conscious rats maintained at low (8 °C), moderate (22 °C), and high (30 °C) ambient temperatures were assessed. Norepinephrine, tyramine, and ephedrine each produced hypothermia at ambient temperature (Ta) 8 °C and hyperthermia at Ta 22 and 30 °C. At Ta 8 °C, the hypothermia in response to norepinephrine, tyramine, and ephedrine was due to decreased metabolic rate (M) whereas at Ta 22 °C the hyperthermia was due to cutaneous vasoconstriction. At Ta 22 °C, the hyperthermia in response to norepinephrine and tyramine was due to cutaneous vasoconstriction whereas the hyperthermia in response to ephedrine was brought about by increased M (due to behavioral excitation). Intracerebroventricular injection of epinephrine produced hypothermia followed by hyperthermia at Ta 8 and 22 °C. The hypothermia was due to decreased M whereas the hyperthermia was due to cutaneous vasoconstriction and increased M. At Ta 30 °C, epinephrine led to a reduction in cutaneous temperature and hyperthermia. Furthermore, i.c.v. administration of phenylephrine produced a decreased M and hypothermia at Ta, 8 °C and an increased M (due to behavioral excitation) and hyperthermia at Ta 30 °C. At Ta 22 °C, phenylephrine produced hyperthermia (due to cutaneous vasoconstriction and increased M) preceded by hypothermia (due to decreased M). Moreover, the temperature effects induced by norepinephrine were antagonized by pretreatment with the adrenoceptor antagonist phentolamine. In general, the data indicate that activation of central adrenoceptors with sympathomimetic drugs inhibits both heat production and heat loss mechanisms in the rat.
Effects of intracerebroventricular injection of d-amphetamine on metabolic, respiratory, and vasomotor activities and body temperatures in the rat
Authors: Lin M. T. , Chandra A. , Chern Y. F. , Tsay B. L.
Published: April 2011

Systemic and central administration of d-amphetamine both produced dose-dependent hypothermia in the rat at ambient temperature (Ta) 8 °C. The hypothermia was brought about solely by a decrease in metabolic heat production. However, at both Ta 22 and 30 °C, d-amphetamine produced hyperthermia accompanied by behavioral excitation. The hyperthermia was due to cutaneous vasoconstriction and increased metabolic heat production (due to behavioral excitation) at Ta 22 °C, whereas at Ta 30 °C the hyperthermia was due to cutaneous vasoconstriction, decreased respiratory evaporative heat loss, and increased metabolism (due to behavioral excitation). Furthermore, both the thermal and the behavioral responses induced by d-amphetamine were antagonized by pretreatment with intracerebroventricular administration of 6-hydroxydopamine (a depletor of central catecholaminergic nerve fibers). The data indicate that, by eliminating the interference of behavioral responses induced, d-amphetamine leads to an alteration in body temperature of rats by decreasing both metabolic heat production and sensible heat loss, probably via the activation of central catecholaminergic receptors.
Unidirectional block in Purkinje fibers
Authors: Waxman Menashe B. , Downar Eugene , Wald Robert W.
Published: April 2011

Three methods of inducing focal conduction disturbances in free-running sheep Purkinje fibers (symmetric and asymmetric focal cooling and asymmetric focal crushing) were explored in 50 preparations. Complete unidirectional block was induced in only a minority of symmetrically cooled preparations whereas the asymmetric lesions generated this conduction disturbance in 80–85% of preparations. The block was more stable when induced by crushing than by asymmetric cooling but was more readily reversible with the latter. The direction of block coincided with the least abrupt gradient in the intensity of the lesion (82–94%), was reversible upon reorientation of the cooling lesion, and was independent of anatomic orientation or pre-existing asymmetries of conduction. The models of unidirectional block described in this paper may be useful in the elucidation of the mechanism of asymmetric conduction disturbances and in studies of the mechanism of action of antiarrhythmic drugs.
The catecholamine precursor L-3,4-dihydroxyphenylalanine inhibits both heat production and heat loss mechanisms in the rabbit
Authors: Lin M. T.
Published: April 2011

The effects of the catecholamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) on the thermoregulatory responses of conscious rabbits to different ambient temperatures (Ta) (2, 22, and 32 °C) were assessed. Intravenous administration of L-DOPA alone, intravenous administration of L-DOPA plus R04-4602 (a peripheral decarboxylase inhibitor), and intraventricular administration of L-DOPA or norepinephrine all produced a hypothermia at Ta 2 °C. The hypothermia was due to a decrease in metabolic heat production (M). On the other hand, L-DOPA or norepinephrine produced both behavioral excitation and hyperthermia at both Ta 22 and 32 °C. At Ta 22 °C, the hyperthermia was due to decreased ear skin blood flow (EBF) and slightly increased M (due to behavioral excitation) whereas at Ta 32 °C the hyperthermia was due to decreased EBF, decreased respiratory evaporative heat loss, and slightly increased M (due to behavioral excitation). Further, the temperature effects induced by L-DOPA were antagonized by pretreatment with 6-hydroxydopamine (a relative depletor of catecholaminergic nerve fibers) but not with haloperidol (a relative blocker of dopaminergic receptors). The data indicate that activation of central adrenergic receptors via the endogenous release of norepinephrine with L-DOPA inhibits both heat production and heat loss mechanisms in the rabbit.