bluuebunny/crossref_metadata_2025 huggingface dataset:
Species differences in histamine receptors in the seminal vesicle
Authors: MacIntosh C. M. , Vohra M. M.
Published: April 2011

Histamine and specific H1- and H2-receptor agonists and antagonists in conjunction with phentolamine and (or) reserpine pretreatment were used to characterize histamine receptor(s) in the seminal vesicle of rat and guinea pig. Stimulation of H1 receptors produced a contraction whereas that of H2 receptors inhibited the contraction evoked by electrical field stimulation. The rat seminal vesicle was relatively refractory to the action of histamine and selective H1- or H2-rcceptor agonists. The evidence, however, does not preclude the presence of a small population of H2 receptors in this preparation. The guinea pig seminal vesicle contained both H1 and H2 receptors but the H1 receptors were dominant. The presence of H2 receptors in the guinea pig seminal vesicle could be demonstrated either with histamine after blockade of the dominant H1 receptor (mepyramine) or with dimaprit, a selective H2-receptor agonist.In a previous study, we reported that the mouse seminal vesicle contained an inhibitory H2 receptor but was virtually devoid of an excitatory H1 receptor. Data from that study and the present one indicate that there are marked qualitative and quantitative differences in the distribution of the two types of histamine receptors in the seminal vesicles of different species.
Pressor effect of tonin in anephric animals
Authors: Schiffrin E. L. , Garcia R. , Gutkowska J. , Boucher R. , Genest J.
Published: April 2011

Tonin was injected intravenously to normal rats without effect on blood pressure. Twenty-four hours after bilateral nephrectomy, tonin produced a dose-dependent pressor effect in rats which was abolished by the angiotensin antagonist [Sar1-Ala8]-angiotensin II. Vascular response to angiotensin II was slightly increased after nephrectomy. Plasma angiotensin II increased significantly after injection of tonin and disappeared biexponentially with a half-life of <1 min for the fast component and 9 min for the slow component. The change in plasma angiotensin II correlated with the elevation in mean blood pressure. No difference in inhibitory power of plasma on tonin activity could be shown between intact and nephrectomized rats. In vitro, the initial velocity of generation of angiotensin II by tonin acting on plasma increased after addition of semipurified rat renin substrate and was significantly greater in plasma of nephrectomized rats. In nephrectomized rabbits, but not in intact ones, a dose-dependent pressor effect was produced by tonin. These data demonstrate the in vivo production of angiotensin II by tonin in an animal model with elevated substrate levels. Together with the in vitro data, these results suggest a role for substrate concentration in the expression of tonin enzymatic activity in vivo.
Dietary linoleic acid and salt-induced hypertension
Authors: Macdonald Murray C. , Kline Robert L. , Mogenson Gordon J.
Published: April 2011

Male Wistar rats chronically fed a low level (0.41%) of linoleic acid (LA) in the diet as supplied by 5% olive oil developed a significant elevation of systolic blood pressure as compared with rats fed either a medium (4.2%) or high (9.4%) level of dietary LA. Chronic excess intake of NaCl (3.75% in the diet) was associated with a significant elevation of blood pressure on all three diets but a low level of LA in the diet exaggerated the salt-induced hypertension. The results suggest that inadequate dietary LA may result in an increase in systolic blood pressure regardless of the sodium content of the diet.
Tissue fractionation studies on the relationship between an atrial natriuretic factor and specific atrial granules
Authors: Bold Adolfo J. de
Published: April 2011

Mammalian atrial cardiocytes contain storage granules, the specific atrial granules, which morphologically resemble granules found in polypeptide hormone producing cells. The number of these granules may be altered by manipulation of water–electrolyte balance in experimental animals hinting at a role for atrial granules in the regulation of such balance. It has been recently shown that rat atrial muscle contains a factor referred to as atrial natriuretic factor. This factor induces a very powerful diuretic and natriuretic response when injected into nondiuretic assay rats. The present investigations were carried out to determine whether there exists any relationship between atrial natriuretic factor and specific atrial granules. Using a tissue fractionation procedure for the isolation of purified rat atrial granules, it was found that the highest relative purification of natriuretic factor was obtained in granule-rich subfractions. This finding suggests that the specific atrial granules may be a storage site for atrial natriuretic factor.
Role of acidosis in the protein wasting of fasting in the rat and the rabbit
Authors: Hannaford Maureen C. , Goldstein Marc B. , Josse Robert G. , Halperin Mitchell L.
Published: April 2011

The purpose of these experiments was to determine if augmented renal ammoniagenesis in chronic metabolic acidosis could increase the negative nitrogen balance during prolonged fasting. To explore this question, rats and rabbits were fasted for up to 10 days because acidosis would markedly augment ammonium excretion in the rat but not in the rabbit. Since the ketoacidosis of fasting was mild in both species (< 2 mM) and ketonuria virtually absent, a hydrochloric acid load was given to stimulate renal ammoniagenesis. Under these conditions, nitrogen balance was significantly more negative during acidosis in the rat but not in the rabbit. This increment in nitrogen excretion appeared as ammonium with no detectable difference in urea nitrogen excretion. Therefore, it appears that if more nitrogen is excreted as ammonium, net protein breakdown increases to furnish the substrate for ammoniagenesis rather than reducing the excretion of the other nitrogenous waste component urea. The implications of these findings will be discussed.
Evidence against a role for lipoxygenase-derived products of arachidonic acid in the lamb ductus arteriosus
Authors: Coceani F. , Jhamandas V. M. , Bodach E. , Labuc J. , Olley P. M. , Borgeat P.
Published: April 2011

The effects of leukotrienes, the leukotriene antagonist FPL55712 (sodium 7-(3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-2-hydroxypropoxy)-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate), and inhibitors of arachidonate lipoxygenase and cyclooxygenase (compound BW755C, 3-amino-1-(m-(trifluoromethyl)-phenyl)-2-pyrazoline; ETYA, 5,8,11,14-eicosatetraynoic acid) were studied in an isolated preparation of ductus arteriosus from mature foetal lambs. Leukotrienes (LT) C4 and D4 produced a modest relaxation of the ductus but only at the highest concentrations tested (10−7 to 10−6 M) and under hypoxic conditions ([Formula: see text], 6–9 Torr (1 Torr = 133.322 Pa)). LTB4 had no effect at any concentration tested. BW755C (10−6 to 10−5 M) and FPL55712 (10−5 M) contracted the hypoxic ductus; however, their action was abolished by pretreatment of the tissue with the cyclooxygenase inhibitor indomethacin (2.8 × 10−6 M). Indomethacin-treated preparations were also unresponsive to ETYA 3 × 10−5 M. The contraction of hypoxic tissues to either BW755C or FPL55712 increased further upon raising the oxygen tension of the medium ([Formula: see text] 591–691 Torr). These findings indicate that leukotrienes and allied compounds formed from lipoxygenase-catalysed reactions do not contribute to prenatal patency of the ductus and are unlikely to have a role in its closure at birth. It is also confirmed that prostaglandin E2 is essential for keeping the vessel patent in the foetus.
Trophic effects of cholecystokinin octapeptide on the pancreas of the Syrian hamster
Authors: Pfeiffer C. J. , Chernenko G. A. , Kohli Y. , Barrowman J. A.
Published: April 2011

Repeated subcutaneous injections of cholecystokinin octapeptide (CCK-OP) to Syrian golden hamsters for 10 days elicited a marked trophic effect on the pancreas, characterized by increased pancreatic weight and increased RNA/DNA ratios with an enhanced content of amylase in the pancreas in treated hamsters. These responses were observed after relatively small doses (100–300 ng CCK-OP ∙ day−1 ∙ 100 g body weight−1) of the hormone over a 10-day period. Although there was a small increase in total pancreatic DNA there was no definite evidence of hyperplasia in response to CCK-OP. DNA synthesis, as measured by histoautoradiography of tritiated thymidine labelled tissues, was increased in pancreatic acinar and islet cells, but not in ductal cells. This investigation, therefore, demonstrates a trophic action of CCK on the pancreas of the hamster similar to that reported for the rat and this may have relevance in studies of carcinogenesis since the hamster is an established species for studying pancreatic cancer.
Effect of pentobarbital anesthesia and surgery on the control of arterial pressure and mesenteric resistance in cats: role of vasopressin and angiotensin
Authors: McNeill J. Robert , Pang Catherine C. Y.
Published: April 2011

We compared the effects of pentobarbital-induced anesthesia and major surgery (laparotomy) on the mesenteric resistance vessels and arterial pressure of cats. Intravenous infusion of sodium pentobarbital (30 mg/kg over 30–60 min) into conscious and unrestrained cats caused only a small increase in superior mesenteric arterial conductance and a small fall in femoral arterial pressure. In contrast to the effects of pentobarbital, major surgery caused marked mesenteric vasoconstrictor and pressor responses. Under these conditions, acute hypophysectomy and infusion of [Sar1,Ala8]angiotension II (saralasin) caused mesenteric conductance and arterial pressure to return towards presurgery control values. The results suggest that the high arterial pressure and constricted state of the mesenteric bed seen in acute experiments appears to be related to surgical stress rather than pentobarbital-induced anesthesia and that both the vasopressin system and the renin–angiotensin system appear to play important roles in the control of arterial presure and the mesenteric resistance vessels under these conditions.
Evidence for on–off control of heat dissipation from the tail of the rat
Authors: Young A. A. , Dawson N. J.
Published: April 2011

Anterior hypothalamic temperature, tail vasoactivity, and tail heat loss were observed in unanaesthetised rats resting at an ambient temperature that was varied between 25 and 35 °C between experiments, but was held constant within an experiment. Vasodilation and vasoconstriction at the tail were qualitatively detectable by the appearance and disappearance of temperature differences between the tail surface overlying the ventral arterial supply, and the lateral venous drainage. Vasodilation detected this way was an abrupt singular event (being either on or off), and preceded subsequent exponential changes in tail surface temperature and heat loss. Within the ambient temperature range of 29–33 °C, the following sequence occurred in a 20-min cycle, despite the noncycling constant environmental and metabolic heat loads: tail vasodilation – 0.2 to 0.4 °C fall in hypothalamic temperature – tail vasoconstriction – 0.2 to 0.4 °C rise in hypothalamic temperature. This behaviour, consistent with the limit-cyclic behaviour of some nonlinear controllers, as well as the abrupt two-state nature of vasoactivity at the rat tail, provides evidence that the mechanism can be described by an on–off control model. In addition, angiography suggests that vasoconstriction rather than countercurrent heat exchange provides the major barrier to core to tail heat flow during the "off" phase.
Ethanol effects on the olivocerebellar system
Authors: Sinclair J. G. , Lo G. F. , Harris D. P.
Published: April 2011

Ethanol (1.5 g/kg i.v.) was found to decrease spontaneous complex spike (CS) activity in cerebellar Purkinje cells in urethane anaesthetized rats while not changing the threshold required to evoke a CS by juxtafastigial stimulation. Thus ethanol does not decrease CS activity by an action at the climbing fibre – Purkinje cell synapse. Tremor induced by harmaline (5 mg/kg i.v.) in unanaesthetized animals was markedly antagonized by ethanol (0.5–2.0 g/kg i.v.) in all animals tested. However, in nine urethane-anaesthetized animals, ethanol markedly reversed the effects of harmaline on Purkinje cells in only two cases and partially reversed the effects in another four cells. Thus, the depressant effects of ethanol on the inferior olive is not totally responsible for the blockade of the harmaline tremor but would account for the decrease in spontaneous CS activity.
Evidence that L-sucrose is resistant to hydrolysis catalyzed by jejunal brush border enzymes
Authors: Dinda P. K. , Beck I. T. , Szarek Walter A. , Hay George W. , Ison Edward R. , Vyas Dolatrai M.
Published: April 2011

The sucrase–isomaltase complex of the intestinal brush border membrane (BBM) catalyzes the hydrolysis of sucrose. The stereospecificity of this enzyme, however, is not known. To investigate this, BBM of hamster jejunum was incubated with D-sucrose or L-sucrose, and the reaction mixture was analyzed using a gas–liquid chromatograph. It was found that D-sucrose was hydrolyzed to its monomers, but L-sucrose remained unhydrolyzed. It is concluded that the sucrase–isomaltase of intestinal BBM of hamster jejunum does not hydrolyze L-sucrose and therefore this enzyme is stereospecific.
Influence of bilateral nephrectomy on selected gastrointestinal bacteria in the rat
Authors: Grunewald Katharine K. , Mitchell Jr. George E. , Tucker R. E. , Langlois Bruce E. , Bruckner Geza G.
Published: April 2011

A series of experiments was designed to investigate the influence of acute renal failure on selected gastrointestinal bacteria. Sprague–Dawley male rats were bilaterally nephrectomized to induce acute renal failure, with sham-operated animals serving as controls. After 48 h animals were sacrificed and the stomachs, upper and lower small intestines, ceca, and colons were excised and subjected to microbial analyses. Lactobacilli and streptococci including enterococci, were 1–2 log counts higher in the stomachs of anephric rats than those of sham-operated controls; lactobacilli were increased similarly in the upper small intestines of these animals. Coliforms including Escherichia coli, and Proteus were 1–2 log counts higher in the lower small intestine of anephric rats than those of sham-operated rats. The decreased gastric pH, increased cecal pH, hypothermia, and delayed gastric emptying observed in nephrectomized rats could partly explain the different microfloras in these animals.
The determination of the instantaneous velocity of axonally transported organelles from filmed records of their motion
Authors: Koles K. J. , McLeod K. D. , Smith R. S.
Published: April 2011

A computational procedure is described for obtaining reproducible, low noise estimates of the instantaneous velocity of axonally transported organelles. Axonally transported organelles were detected in myelinated nerve fibers from Xenopus laevis by dark-field microscopy. The motion of the organelles was recorded on motion picture film at 3 frames/s, and the position of organelles travelling in the retrograde direction was obtained as a pair of x (axial) and y (transverse) coordinates at each 0.33-s interval. The trend in organelle movement with time was calculated for each of the series of x and y coordinates by linear regression. This trend was removed from the measurements of x and y to yield sets of trend-free displacements. The trend yielded a measure of the mean velocity of the organelle in each of the two orthogonal directions. Power spectra of the deviations in x and y about the trend were calculated. For 133 particles studied, 99% of the power in the trend-free deviations occurred at frequencies below 0.3 Hz. The peak power in the x and y deviations occurred at a frequency of 0.1 Hz or less. Positional deviations about the trend were treated with a discrete 21-term differentiating filter that attenuated frequencies above 0.3 Hz. Instantaneous velocities for the organelles were obtained by adding the result of the band-limited differentiation to the appropriate estimates of mean velocity. The 21-term method was compared with a commonly used 2-term approximation to a differentiator and was shown to produce velocity estimates with about one order of magnitude less error. Estimates of organelle velocity obtained with the 21-term method indicate that saltatory particle motion may be viewed either as a smooth variation of particle velocity with respect to time or as an irregular, or discontinuous, variation of velocity with respect to particle position.
Inhibition of gastric H+ secretion, K+-ATPase and K+-phosphatase by estradiol in vivo and in vitro
Authors: Limlomwongse L. , Piyachaturawat P.
Published: April 2011

The effect of estrogen on the gastric acid secretion and H+-transporting enzymes, K+ -ATPase and K+-phosphatase, were investigated in the rat. The maximum H+ secretory rate in response to 1 mM histamine was significantly reduced (P < 0.05) in both the isolated gastric mucosa obtained from the rats treated with estradiol in vivo for 7 days and the mucosa directly incubated in vitro with estradiol. The inhibitory effect on the gastric enzyme activities in vitro showed a dose-dependent pattern of a noncompetitive type. The result suggested that estradiol may have a direct action on the gastric H+ secretion by inhibiting the H+ transport enzyme activities.
Some aspects of porphyrin neurotoxicity in vitro
Authors: Riopelle R. J. , Kennedy J. C.
Published: April 2011

Using a dissociated primary sensory neuron culture system, it is observed that some naturally occurring porphyrins produce dose-dependent neurotoxicity as measured by neuron death and by inhibition of the neurite outgrowth induced by Nerve Growth Factor (NGF). However, the porphyrin precursor δ-aminolcvulinic acid (δ-ALA) is not toxic up to millimolar concentrations within a 30-h time period. Two synthetic porphyrins, tetraphenylporphine sulfonate (TPPS) and hematoporphyrin derivative (HPD), have also been shown to be toxic in vitro.Cultures and cocultures of isolated populations of neurons and glia of central and peripheral nervous system origin may prove advantageous in the study of porphyrin influences on the intact nervous system. This in vitro assay system can complement in vivo paradigms and may be useful for rapid quantitative screening for neurotoxicity of radiation sensitizers including the synthetic porphyrins and other chemotherapeutic agents.
A comparison of some pharmacological effects of naloxone and N-methylnaloxone in mice
Authors: Ramabadran K. , Suaudeau C. , Jacob J. J. C.
Published: April 2011

The effects of N-methylnaloxone following subcutaneous and intracerebroventricular administrations on nociception were investigated using the hot plate technique. Unlike naloxone, subcutaneous administration of N-methylnaloxone did not enhance the nociceptive reactions. In contrast, intracerebroventricular injection of N-methylnaloxone produced antinociception and tremor. Compared with naloxone, N-methylnaloxone was very weak in precipitating the signs of abstinence in mice rendered acutely dependent on morphine. Two factors, poor penetration into the central nervous system and steric hindrance, might render N-methylnaloxone very weak and hence both these factors must be taken into consideration while analyzing the effects following quaternary derivatives of opioid antagonists.
Central injections of spiperone and GABA: attenuation of angiotensin II stimulated thirst
Authors: Jones D. L. , Mogenson G. J.
Published: April 2011

This study investigated the effects of injecting spiperone or γ-aminobutyric acid (GABA) into the brain on drinking induced by angiotensin II injected into a lateral cerebral ventricle of the rat. Injections of 12.5 pM of angiotensin II elicited water intakes averaging 10 mL in 15 min with latencies of less than 3 min. Spiperone, a dopamine antagonist injected into the nucleus accumbens produced dose-dependent reductions in water intake and number of laps while increasing the latency to drink. Injections of GABA into the ventral tegmental area produced dose-dependent reductions in water intake and number of laps without altering latency to drink or lap volume. GABA injected into the globus pallidus reduced drinking in a manner similar to that described for spiperone injected into the nucleus accumbens when angiotensin II was the dipsogenic agent but was totally without effect on drinking induced by carbachol injections. These results indicate that a proposed neuronal circuit composed of GABA input to ventral tegmental area neurons, dopamine input from the ventral tegmental area to nucleus accumbens neurons, and subsequent GABA input from the nucleus accumbens to globus pallidus neurons may interact with the goal-directed behaviour, drinking, elicited by central angiotensin II administration. Further, they provide evidence that this neuronal circuit may be part of a functional interface for response initiation.
Metabolic effects of two frequencies of short-term surface electrical stimulation on human muscle
Authors: Houston Michael E. , Farrance Brian W. , Wight Robyn I.
Published: April 2011

The acute effects of two different frequencies of electrical stimulation on the metabolism of the vastus lateralis muscle were studied in young male and female adults. The quadriceps muscle group of one leg was stimulated for 60 min using surface electrodes that delivered square pulses of 0.6 ms duration, either continuously at 10 Hz (n = 5) or intermittently (n = 5) at 50 Hz (12 s stimulation, 48 s recovery). Biochemical analyses revealed no significant differences in glycogen or metabolite concentrations between the two conditions. Muscle lactate and citrate concentrations were increased (p < 0.05) for both conditions, but ATP and CP concentrations were not significantly changed from rest values after stimulation. Glycogen concentrations decreased (p < 0.05) by 24.6 and 29.1 mmol glucose units/kg after 60 min of 50 Hz and 10 Hz stimulation, respectively. Muscle fibres were identified as slow twitch (ST) and fast twitch a and b (FTa and FTb) on the basis of myofibrillar ATPase activity. Estimates of glycogen depletion in different fibre types using histochemical techniques revealed that FTa and FTb fibres had lower glycogen contents than ST fibres after 10 Hz stimulation whereas glycogen was moderately reduced in approximately 50% of all fibre types following 50 Hz stimulation. The modest changes observed in muscle metabolism following 60 min of stimulation were less than has been noted following traditional exercise, and suggest that only some of the muscle fibres were activated in the stimulated muscles at the depth where biopsy samples were removed.
Trophic effects of chronic bethanechol on pancreas, stomach, and duodenum in rats
Authors: Morisset Jean , Jolicoeur Lyne , Caussignac Yves , Solomon Travis E.
Published: April 2011

Rats received a daily injection of 2, 6, or 12 mg kg−1 bethanechol for 7 or 14 days. Pancreatic weight and content of protein, amylase, and chymotrypsinogen were increased in a dose and time dependent fashion by bethanechol. After 14 days of treatment with the highest dose, pancreatic weight and total pancreatic DNA content increased to 1.18 times control (P < 0.05) while protein increased to 1.25, amylase to 1.85, and chymotrypsinogen to 1.72 times control. There was a slight increase in oxyntic gland area weight in bethanechol-treated rats, but content of DNA, protein, and pepsinogen were not changed. Bethanechol had no effect on duodenal weight or content of DNA, protein, or maltase. Acute administration of 12 mg kg−1 bethanechol increased circulating gastrin levels for at least 4 h in unanesthetized rats. We conclude that long-term treatment with a cholinergic agonist produces pancreatic hyperplasia and increases protein and enzyme content. Under the conditions of this study, no effects were seen on oxyntic gland area of stomach or duodenum.
Effects of dietary cholesterol level and type of dietary carbohydrate on hepatic and plasma sterols in the gerbil
Authors: Andersen D. B. , Holub B. J.
Published: April 2011

The influence of dietary cholesterol and type of carbohydrate on the level of free cholesterol, esterified cholesterol, and the type of cholesteryl esters in the liver of the Mongolian gerbil, Meriones unguiculatus, was studied by a series of experiments. Semipurified diets were fed in which the level of cholesterol was comparable to human intakes (0.1% by weight) or higher (0.5%) and the carbohydrate source was starch or sucrose or a mixture thereof. All diets were devoid of bile acid and contained relative amounts of carbohydrate, protein, fat, and type of fat which approached human intakes in North America. Free cholesterol levels in liver were 60–140% greater and 15–30% greater when diets were supplemented to contain sterol levels of 0.5 and 0.1%, respectively, whereas hepatic cholesteryl ester levels were 11- to 23- fold greater and 2- to 3-fold greater, respectively. Levels of cholesterol (both free and esterified) in plasma were 175–725% greater in animals consuming 0.5% dietary cholesterol and 30–105% greater in gerbils ingesting 0.1% cholesterol as compared with levels in gerbils fed a basal (unsupplemented) diet. The type of dietary carbohydrate had a moderate influence on cholesterol levels in liver and plasma when dietary cholesterol was supplied at 0.5%. The percent contribution of 18:1 fatty acid to the liver cholesteryl esters was greater in cholesterol-supplemented gerbils, while the proportions of 16:0 and 18:2 acids were lower. These results indicate that the gerbil is highly sensitive to low levels of dietary cholesterol in diets which are also free of bile acid, in contrast to many other species, including the laboratory rat. The present findings support the usefulness of the gerbil model for studying the influence of dietary sterol on cholesterol metabolism.
Ion transport by the pig colon: effects of theophylline and dietary sodium restriction
Authors: Argenzio R. A. , Lebo Deborah
Published: April 2011

The effect of theophylline on colonic electrolyte transport was examined in an isolated, static loop system of the pig colon. The presence of theophylline abolished the net absorption of Na and water and increased the net secretion of HCO3. The net absorption of Cl or acetate was unaffected. In pigs adapted to a saltfree diet, the net absorption of Na was increased twofold from that observed in pigs fed the normal diet; however, the basal rate of net HCO3 secretion was unchanged. In the presence of theophylline, the saltfree diet restored net Na absorption to control levels, whereas the theophylline-induced increase in the rate of net HCO3 secretion was sustained. Results suggest that the relative rates of net Na and HCO3 transport are partially controlled by independent systems and indicate that normal rates of net absorption can be restored in the presence of a parallel secretory process.
Coronary artery compliance in the dog
Authors: Klassen G. A. , Wong A. Y. K.
Published: April 2011

Measurement of left anterior descending coronary arterial pressure, phasic coronary flow, and intramyocardial pressure in an open-chest dog provided data, which when entered into the computer model of the coronary circulation, permitted calculation of coronary artery compliance and resistance during systole and diastole. Resting in vivo compliance averaged 0.21 × 10−3 mL/mmHg (1 mmHg = 133.322 Pa) while systolic resistance averaged 4.05 mmHg∙min−1∙mL−1 and during diastole 2.06 mmHg∙min−1∙mL−1. Left stellate ganglion stimulation or vasodilation caused minimal changes in compliance but glutaraldehyde applied to arterial wall caused a decrease in compliance. Sympathetic stimulation and vasodilation decreased both diastolic and systolic resistance. Transmural distribution of coronary flow was not significantly altered by the experimental changes in compliance and resistance.
Oxytocin action: lipid metabolism in adipocytes from homozygous diabetes insipidus rats (Brattleboro strain)
Authors: Hanif K. , Goren H. J. , Hollenberg M. D. , Lederis K.
Published: April 2011

Oxytocin, like insulin, stimulates glucose oxidation in normal rat adipocytes. Fat cells from homozygous Brattleboro rats that exhibit diabetes insipidus (HoDI animals) and that have a normal number of oxytocin receptors, however, are unable to respond to oxytocin in terms of glucose oxidation. We now report that in adipocytes from HoDI animals that are responsive to insulin, oxytocin was also unable to stimulate lipogenesis. In contrast, oxytocin like insulin was able to inhibit epinephrine-stimulated lipolysis in adipocytes from HoDI animals. Thus, in HoDI adipocytes, the results indicate that the receptor–effector system is only partially defective.
Flunitrazepam binding sites in rat diaphragm. Receptors for direct neuromuscular effects of benzodiazepines?
Authors: Wilkinson M. , Grovestine Dale , Hamilton J. T.
Published: April 2011

The evidence for direct muscle relaxant effects of benzodiazepines is controversial. We now show that a crude membrane preparation of rat diaphragm possesses binding sites for [3H]flunitrazepam (FNZ). Scatchard analysis gave a binding site density of 1689 ± 143 fmol/mg protein (Kd = 25.6 ± 2.6 nM). These sites are of the "peripheral" type since clonazepam fails to displace [3H]FNZ as effectively as R05-4864 (IC50 values: 7.5 × 10 6 M and 8 × 10−9 M, respectively). Diazepam is almost as effective as R05-4864 and potently displaces [3H]FNZ binding (IC50 = 3 × 10−8 M). We propose that the previously described effects of diazepam on rat diaphragm are mediated through high-affinity binding sites.
Effect of cholesterol feeding and gender on the response of the isolated rat heart to hypoxia
Authors: Moffat Margaret P. , Karmazyn Morris , Dhalla Naranjan S.
Published: April 2011

The effect of hypoxic perfusion on isolated hearts from male and female rats fed either a control or 2% cholesterol supplemented diet was studied. Initiation of hypoxia produced a rapid decline in rate of hearts from either male or female animals irrespective of diet regimen. However, hearts from male rats fed a control diet exhibited a significantly higher (P < 0.01) resting rate during normoxic perfusion when compared with hearts from cholesterol-fed animals. Hypoxia also produced a rapid loss of myocardial contractile force and this effect was influenced by neither diet treatment nor animal gender. Similarly, there was little change in time to peak height of developed tension due to diet. Contracture development during hypoxic perfusion was significantly higher in hearts from female rats fed a cholesterol-supplemented diet compared with hearts from control diet fed female animals, whereas no changes were observed due to diet in hearts from male animals. Coronary resistance was increased as a result of hypoxic perfusion. In hearts from cholesterol-fed male rats this effect was substantially attenuated. Conversely, cholesterol supplementation resulted in a higher (P < 0.05) coronary resistance in hearts from female animals either during normoxic or the early period of hypoxic perfusion. Prostacyclin synthesis as measured by immunoreactive 6-keto-PGF1α efflux did not differ between hearts from either male or female rats during normoxic perfusion. Hypoxia significantly reduced 6-keto-PGF1α efflux from hearts of cholesterol-fed male rats whereas it produced no effect in any other treatment category. Our results demonstrate a substantial contribution of dietary cholesterol and animal gender in the response of the isolated rat heart to hypoxic perfusion.
Binding of [3H]des-Arg9-BK to rabbit anterior mesenteric vein
Authors: Barabé J. , Babiuk C. , Regoli D.
Published: April 2011

Binding studies of [3H]des-Arg9-BK have been performed on pieces of rabbit anterior mesenteric veins. Kinetic studies have permitted us to evaluate an affinity constant of 1.04 × 10−7 M, which is not so different from the apparent affinity constant determined by bioassay (1.6 × 10−7 M). Furthermore, inhibition of the binding of [3H]des-Arg9-BK with various kinins results in an order of potency of kinins very similar to that observed in the bioassay. Taken together, these results suggest that we are dealing with binding sites which might be the same as those subserving the biological action of des-Arg9-BK (pharmacological receptors). The preincubation of tissues in Krebs' solution brings about an increase of the specific binding from 0.06 pmol/mg of wet weight at time 0 to 0.75 pmol after 24 h; cycloheximide inhibits this increase for at least 6 h. Veins taken from animals treated with LPS, which have shown an increase in sensitivity compared with veins extracted from untreated animals, have a higher number of specific binding sites for [3H]des-Arg9-BK. The results support the hypothesis that the increased response of tissues to des-Arg9-BK is due to the de novo synthesis of receptors for kinins in some experimental and pathological conditions.
Effects of kinins on isolated blood vessels. Role of endothelium
Authors: Regoli D. , Mizrahi J. , D'Orléans-Juste P. , Caranikas S.
Published: April 2011

Bradykinin (BK) and des-Arg9-BK were used to determine whether the stimulatory and inhibitory actions of the kinins in various isolated vessels require the presence of endothelium and may be mediated by arachidonic acid metabolites. It was found that the presence of intact endothelium is required only for the relaxation of the dog common carotid artery in response to bradykinin. Stimulatory actions of both BK and des-Arg9-BK in arterial (rabbit aorta) and venous (rabbit jugular and mesenteric vein) smooth muscle do not require the presence of endothelium. Inhibition of the arachidonic acid cascade at various levels affects the relaxing action of acetylcholine (rabbit aorta and dog common carotid artery) while being inactive against both the relaxing (dog common carotid artery) and contractile actions (rabbit aorta, rabbit jugular and mesenteric veins) of bradykinin and des-Arg9-BK. Inhibitors of the arachidonic acid cascade also do not affect the inhibitory action of isopropylnoradrenaline on the rabbit aorta. The present results indicate that stimulant actions of kinins in isolated vascular smooth muscles do not require the presence of endothelium. Endothelium is required for the inhibitory actions of acetylcholine and bradykinin but not for that of isopropylnoradrenaline on the dog carotid artery. Moreover, the inhibition of arachidonic acid metabolism only affects the response of isolated vessels to acetylcholine. The present results suggest that several mechanisms may be involved in the inhibition of vascular tone by vasodilators.
Insulin and glucagon response during hemorrhage induced hyperglycemia
Authors: Lautt W. Wayne , Martens Elizabeth S. , Légaré Dallas J.
Published: April 2011

Rapid hemorrhage to 50 mmHg (1 mmHg = 133.322 Pa) in the pentobarbital-anesthetized cat leads to severe hyperglycemia which declines only slightly by 90 min of hemorrhage. Insulin levels decline to less than one-half of control levels and remain low throughout, despite the hyperglycemia. Glucagon levels decline at 15 min but are significantly elevated by 90 min. These data confirm that the hepatic glycogenosis is controlled almost entirely by hepatic sympathetic nerves and adrenal secretions with no role for elevated glucagon levels at the early stages in hemorrhage. Hepatic denervation leads to lesser insulin suppression and greater glucagon elevation at later times (45 and 90 min), suggesting that intact hepatic nerves are required for a normal pancreatic response. Hepatic sympathectomy did not produce these effects. Insulin responses remained normal, but glucagon levels were suppressed throughout the entire experiment in sympathectomized cats. The data suggest that hepatic nerves may modulate insulin and glucagon levels during hemorrhage in an unknown manner.
Effects of tertiary and quaternary derivatives of aminomethylenedioxyindenes on some experimental arrhythmias
Authors: Lynch Joseph J. , Rahwan Ralf G. , Brumbaugh Richard J. , Witiak Donald T.
Published: April 2011

The 2-n-propyl- and 2-n-butyl-3-dimethylamino-5, 6-methylenedioxyindene hydrochlorides are intracellular calcium antagonists with coronary dilating and antiarrhythmic effects against ouabain- and calcium-induced arrhythmias. In the present study, pretreatment with these tertiary methylenedioxyindenes afforded significant protection against the calcium-dependent arrhythmias induced by chloroform in mice. On the other hand, their antiarrhythmic activity against aconitine- and metha-choline-induced arrhythmias in rats (in which calcium does not play a primary etiological role) was suggestive but not impressive. The quaternary derivative, 2-n-butyl-5, 6-methylenedioxy-3-trimethylammonium iodide, which was synthesized with the expectation of being devoid of antiarrhythmic activity owing to its exclusion from the intracellular compartment, unexpectedly demonstrated greater antiarrhythmic potency than the tertiary analogues against calcium-induced arrhythmias in rats and chloroform-induced arrhythmias in mice. Like the tertiary methylenedioxyindenes, the protective activity of the quaternary analogue against arrhythmias induced by aconitine or by methacholine in rats was suggestive but not impressive. Because of the relative inactivity of the quaternary methylenedioxyindene in vitro, it is proposed that its in vivo activity may be due either to metabolic activation or to concentration in cardiac tissue in sufficient quantity to allow diffusion into cardiac cells down a concentration gradient or to alter membrane electrophysiological properties to the extent of exerting antiarrhythmic activity.
Stimulation-evoked changes in extracellular K+ and Ca2+ in pyramidal layers of the rat's hippocampus
Authors: Krnjević K. , Morris M. E. , Reiffenstein R. J.
Published: April 2011

In urethane-anaesthetized rats, ion-selective microelectrodes recorded changes in extracellular K+ and Ca2+ concentrations (Δ[K+]o and Δ[Ca2+]o in pyramidal layers of the hippocampus (mostly in area CA1), which were evoked by fimbrial – commissural stimulation. [K+]o increased linearly with frequency of stimulation up to a critical frequency, in the range of 2–5 Hz, where bursts of population spikes appeared, and then rose rapidly to reach a ceiling of 9–12 mM, During continued stimulation, [K+]o remained well above the resting level of about 3.0 mM. At the end of stimulation [K+]o returned to the base line with a half time of 4–8 s, and a minor undershoot of [Formula: see text] was detectable for 1–2 min. When stimulating at frequencies above the critical value, a sharp fall in [Ca2+]o (by an average of one-third below the mean resting level of 1.4 mM) consistently started 1–5 s after the onset of the rapid phase of Δ[K+]o. [Ca2+]o typically reached a minimum in 5–10 s and immediately started to return towards the base line. The recovery of [Ca2+]o was often accelerated by an overshoot of up to 0.3 mM; this was followed by a delayed phase of low [Ca2+]o for another 2–3 min. During prolonged stimulation at frequencies near 7 Hz, both [Ca2+]o and [K+]o fluctuated periodically, in time with the appearance and disappearance of bursts of population spikes. Comparable observations were made in area CA2 – 3 (just external to CA1); in the deeper areas of CA3, in CA4, and in the dentate gyrus, major changes in [K+]o and [Ca2+]o (as well as bursts of population spikes) were evoked only by prolonged fimbrial stimulation at higher frequencies ([Formula: see text]). Thus, although adequate repetitive stimulation of fimbrial–commissural inputs evokes sharp but opposite changes in [K+]o and [Ca2+]o, the fall in [Ca2+]o is consistently much briefer than the rise in [K+]o, presumably because of the evanescent character of postsynaptic Ca2+ spikes.
Effect of stimulating right atrial receptors on renal blood flow
Authors: Karim F. , Kaufman S. , Kappagoda C. T.
Published: April 2011

This investigation was undertaken to determine the effect of stretching the superior vena caval – right atrial (SVC–RA) junction and the right atrial appendage on blood flow to the kidney (RBF) and to establish whether any changes observed were influenced by the input from the baroreceptors in the carotid sinus. The experiments were performed on seven dogs, anaesthetized with α-chloralose. The systemic arterial (i.e., renal perfusion) pressure was held constant. At a carotid sinus pressure (CSP) of 59.0 ± 1.2 mmHg (1 mmHg = 133.322 Pa), the RBF increased from 218 ± 16.1 to 231.7 ± 18.4 mL/min per 100 g renal mass (p < 0.025). At a CSP of 88.0 ± 3.5 mmHg, the RBF increased from 230.1 ± 19.2 to 237.1 ± 19.2 mL/min per 100 g renal mass (p < 0.05). At a CSP of 137 ± 3.7 mmHg there were no significant changes in RBF. These responses were abolished by cutting (four dogs) or cooling the vagi (one dog only). In a subsidiary investigation it was shown that stretching the SVC–RA junction activated receptors in the endocardial surface of the right atrium which discharged into myelinated fibres in the vagi, having an average conduction velocity of 8.1 m/s (range 3.8–15). It is concluded that stimulation of right atrial receptors increases the RBF and that this response is influenced by the input from the barorceptors in the carotid sinus.
Endorphins mediate overshoot of substance P-induced facilitation of a spinal nociceptive reflex
Authors: Yashpal Kiran , Henry J. L.
Published: April 2011

In the awake restrained rat the intrathecal administration of substance P to the lumbar spinal cord abruptly but transiently reduces reaction time in the tail-flick test. Interestingly, this hyperalgesie effect is followed by an increased response time, i.e., a hyperalgesia, which lasts less than 10 min. Administration of naloxone reduces the reaction time. It leaves the initial hyperalgesia unaltered but blocks the hypoalgesia. These results are interpreted as indicating that the initial effect of substance P is independent of any direct or indirect action mediated by opiate receptors. On the other hand, however, the antagonism of the hypoalgesia by naloxone suggests that this response is mediated via opiate receptors and, as substance P and opiates appear not to have any direct interaction at the cellular level, the endorphin-mediated hypoalgesia appears to be reflex in nature. Thus, the rebound overshoot of the response to substance P is visualized as an endorphin-mediated reflex activated by the increased transfer of nociceptive information provoked by substance P. The concept is proposed, therefore, that the transfer of nociceptive information is controlled by a servomechanism, or, in physiological terms, this transfer is under homeostatic control. Indeed, as naloxone itself reduces reaction time, it appears that an endogenous opioid is acting tonically to depress this transfer, at least under the conditions of the present experiments.
Drug-induced changes in fetal breathing activity and sleep state
Authors: Jansen Arno H. , Ioffe S. , Chernick V.
Published: April 2011

Drugs reported to stimulate fetal breathing (FB) were injected into a femoral vein of near-term fetal iambs during rapid eye movement (REM) and non-REM (NREM) sleep. The primary response to NaCN, 0.25–0.5 mg, a dose which did not flatten the electrocorticogram, was a brief burst of gasping in any sleep state. When injected during REM sleep, NaCN caused the cessation of spontaneous FB and the onset of gasping. Stimulation of FB was observed infrequently. Caffeine (10 mg) and doxapram (3 mg) frequently caused an immediate change in sleep state or arousal. The incidence of FB increased concomitantly with a change to REM sleep or wakefulness (W), but FB still ceased with the onset of NREM sleep. When administered during an episode of spontaneous FB during REM sleep, both caffeine and doxapram caused stimulation of the frequency and depth of breathing. Pilocarpine (4 mg) caused arousal and gasping followed by prolonged vigorous breathing that was dependent on intact carotid sinus nerves, Indomethacin (120 mg over several hours) did not affect sleep states but induced FB in both NREM and REM sleep. In summary, in the fetus the primary effect of NaCN is to suppress spontaneous FB and induce gasping and the effects of pilocarpine, caffeine, and doxapram are intimately related to sleep states or arousal. Indomethacin causes the conversion from episodic fetal to continuous postnatal-type breathing. These data indicate the importance of assessing fetal state of consciousness in interpreting the respiratory response to drugs.
Potent vasoconstriction of the isolated perfused rat kidney by leukotrienes C4 and D4
Authors: Rosenthal A. , Pace-Asciak C. R.
Published: April 2011

Chemically synthesized leukotriene C4, D4, and E4 have been compared for their effects on the isolated Krebs-perfused rat kidney, rat stomach strip, and guinea pig ileum. C4 was more potent than D4 or E4 at all concentrations tested in contracting the rat stomach strip and in constricting the isolated rat kidney, while D4 was more potent than C4 or E4 in contracting the guinea pig ileum. While the effect of leukotrienes on the isolated kidney was blocked dose dependantly by FPL 55712, a blocker of leukotriene action, it was not blocked by the presence of either indomethacin, a cyclooxygenase blocker, or OKY-1581, a blocker of thromboxane synthesis. These results indicate that leukotriene action in the kidney is of a direct nature and is not mediated via activation of the prostaglandin pathway, especially thromboxane A2 synthesis.
Release of intestinal diamine oxidase by histamine in rats
Authors: Wollin Armin , Navert Henri
Published: April 2011

Diamine oxidase activity was measured in the intestinal mucosa, lymph, and in the serum of rats, to determine whether histamine, a substrate of diamine oxidase, liberates this enzyme from its mucosal storage site(s). Histamine induced a sharp rise in intestinal lymph flow, lymph protein, and lymph diamine oxidase, lasting less than 1 h after the histamine injection. The rise in lymph diamine oxidase activity was dose dependent over a narrow concentration range (0.05–0.2 mmol/kg, i.v. and 0.15–0.6 mmol/kg i.d.). It did not correlate with the dose dependent increase in lymph flow or lymph protein. A single maximal intraduodenal dose of histamine caused a 41.6-fold increase in the lymph diamine oxidase activity and a 2.4-fold increase in the serum enzyme level temporarily. A second injection of histamine, 2 h after the first, resulted in a comparatively smaller increase in the lymph enzyme. The extent of the reduction was dependent on the magnitude of the first injection. The results suggest that histamine causes a limited liberation of diamine oxidase from the intestinal mucosa. The function of this enzyme release may be a protective response by the mucosa to reduce toxic levels of free histamine, either liberated by the mucosal tissue or absorbed from the intestinal lumen.