bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of chronic alcohol consumption on myocardium catecholamine concentration in rats
Authors: Rossi Marcos A.
Published: April 2011

In this study, the catecholamine levels of the myocardium in both well-nourished and malnourished alcohol-fed rats were examined. Alcohol has been administered to rats for 16 weeks. Rats fed a diet containing alcohol corresponding to 40% of total caloric intake and inadequate amounts of calories and nutrients showed increased levels of noradrenaline in the heart whereas the controls did not (alcohol-fed rats, 0.888 ± 0.050 μg/g wet tissue weight; controls, 0.668 ± 0.025 μg/g). In addition an increase in heart ratio (gram heart weight/kilogram body weight) could be also observed (alcohol-fed rats, 3.17 ± 0.10; controls, 2.65 ± 0.05). However, between well-nourished rats fed alcohol as 35% of the caloric intake and pair-fed controls there were no differences in catecholamine concentration (alcohol-fed rats, 0.729 ± 0.068 μg/g; pair-fed controls, 0.738 ± 0.069) and heart ratio (alcohol-fed rats, 2.84 ± 0.15; pair-fed controls, 2.75 ± 0.09). From these results, it is concluded that chronic consumption of alcohol induces an increase in myocardium noradrenaline concentration and heart hypertrophy only when it is associated with malnutrition, i.e., alcohol by itself does not alter either of these parameters. Moreover, it can be speculated that continued exposure to high levels of catecholamine may play a role in the development of myocardial hypertrophy.
Differential sensitivity of regional vascular beds in the dog to low-dose prostacyclin infusion
Authors: Einzig Stanley , Rao Gundu H. R. , White James G.
Published: April 2011

The effect of low-dose prostacyclin (PGI2) infusion on abdominal organ, regional central nervous system, and regional myocardial blood flow distribution was studied in 14 open-chested, anesthetized dogs. Blood flow was measured using the radioactive microsphere technique and left atrial (LA) injection of 15-μm spheres. Continuous LA PGI2 infusion (25–35 ng/kg per minute) significantly (P < 0.05 to P < 0.005) increased renal cortical (+13%), splenic (+20%), small intestinal (+41%), large intestinal (+54%), fundic mucosal (+53%), and antral mucosal (+65%) blood flows whereas pancreatic, gallbladder, and hepatic (arterial) flow remained unchanged. Within the central nervous system blood flow increased in the medulla (+18%) and cerebral cortical gray matter (+17%) but was unchanged in the cervical spinal cord, pons, dorsal thalamus, cerebellum, caudate nucleus, and cerebral white matter. Atrial and ventricular myocardial blood flows and masseter muscle blood flow were unchanged during PGI2 administration. Thus blood flow changes are variable between and within regional vascular beds during low-dose PGI2 infusion in the dog.
Ultrastructural study of guinea pig tracheal smooth muscle and its innervation
Authors: Jones Thomas R. , Kannan Mathur S. , Daniel Edwin E.
Published: April 2011

The ultrastructure of guinea pig tracheal smooth muscle and its innervation was studied by transmission electron microscopy. Smooth muscle cells were arranged into bundles separated by collagen and connective tissue cells. Gap junctions were found only rarely between adjacent smooth muscle cells. Bundles of axons (predominantly unmyelinated) were seen on the periphery of the muscle bundles. Some penetrated deep into the bundles and a few made close neuromuscular contacts (< 20 nm). Such a spatial arrangement of nerves and smooth muscle suggests a potential for nervous control and limited myogenic activity. Axon profiles containing small agranular vesicles characteristic of cholinergic nerves and small granular vesicles characteristic of adrenergic nerves were seen in close association with airway smooth muscle and with one another. Some large granular vesicles were associated with varicosities of both nerve types. Quantitative studies demonstrated a preponderance of cholinergic over adrenergic nerve profiles in both upper and lower segments. Varicosities, characteristic of adrenergic nerves, were observed more frequently in upper compared with lower segments; however, observed differences were not significant. The morphological findings are consistent with the control functions exerted by cholinergic and adrenergic nerves but provide no basis for control by nonadrenergic inhibitory nerves.
Potentiation and inhibition of nicotinic effects on striated muscle by the tetramine disulfide benextramine
Authors: Benfey B. G. , Brasili L. , Melchiorre C. , Belleau B.
Published: April 2011

In low concentrations (0.3-3 μM) the tetramine disulfide benextramine (BHC; N,N′-bis[6-(o-methoxybenzyiamino)-n-hexyl]cystamine) potentiated the contracture of the isolated frog rectus abdominis muscle caused by acetylcholine but in the presence of physostigmine or in a higher concentration (10 μM) it inhibited it. Benextramine only inhibited the contracture caused by carbachol or butyrylcholine. The all-carbon analog of benextramine only inhibited the effect of acetylcholine. The inhibitory effects of benextramine and its carbon analog were noncompetitive and readily reversible but the potentiating effect of benextramine was not readily reversible.
A reevaluation of the refractory period following the estrogen-induced luteinizing hormone surge in the rhesus monkey
Authors: Weick Richard F.
Published: April 2011

A refractory period of 6-8 days following the estrogen-induced luteinizing hormone (LH) surge in the rhesus monkey has been reported, the estrogen having been applied as injections of estradiol benzoate. This was reinvestigated using Silastic capsules filled with estradiol-17β. Mature intact female rhesus monkeys were given two successive exposures to estrogen, each of 48 h duration. In one experiment the second exposure started 4 days after the capsules were first implanted (2 days after removal), in the second experiment, 3 days after implantation (1 day after removal). LH surges were seen in response to both estrogen treatments in both experiments. The results suggest that a period of exposure to relatively low estrogen levels is required before a second LH surge can be elicited. This period of time can be as short as 24 h.
Diurnal variation of thermal resistance in rats
Authors: Isobe Y. , Takaba S. , Ohara K.
Published: April 2011

Effects of photoperiod on heat resistance were studied in 88 rats by observing their survival times in a hot environment (42.5 °C). Prior to the experiments individual rats were exposed to a given heat (42.5 °C) at a definite time of day and a "predicted survial time" in a given heat in individual rats was obtained. Rats were then divided into eight groups (with nine rats in each group) so as to ensure intergroup homogeneity regarding their predicted survival time and were exposed to heat at different times of day (every 3 h) until they were exhausted.It was found that the heat resistance varied with the time of day. In the eight groups kept under a normal light–dark cycle (L, 0700–1900; D, 1900–0700), heat resistances were observed to be significantly higher in the light phase than in the dark phase. Lethal body temperature was not correlated with the heat resistance. In two other groups (n = 8) kept under conditions reversed from the normal lighting cycle, resistance was higher in the nighttime (corresponding to the light phase when the rats were kept in the reversed lighting cycle) than in the morning (corresponding to the dark phase), these changes being accompanied by a phase shift of the diurnal changes in body temperature.
Effect of heavy metals and lanthanum on sugar transport in isolated guinea pig left atria
Authors: Bihler I. , Hoeschen L. E. , Sawh P. C.
Published: April 2011

The effect of heavy metals on sugar transport in fully resting guinea pig left atria was studied by measuring the tissue–medium distribution of 3-methylglucose. Basal sugar transport was increased significantly by all heavy metals tested (Co2+, Ni2+, Zn2+, Mn2+ (2 mM)) and by La3+ (0.05 mM) but 1 mM La3+ had no effect. The stimulation of sugar transport by insulin, hyperosmolarity, K+-free medium, or 10−5 M ouabain was strongly antagonized by Ni2+, Zn2+, and La3+ but was unaffected by Co2+ and Mn2+. The heavy metals did not affect intracellular Na2+ and K+, whether in the basal state or when the Na+ pump was depressed by ouabain or K+-free medium. The data suggest that Ca2+ antagonistic ions may affect sugar transport both by inhibiting Ca2+ influx and by competing with Ca2+ for specific binding sites presumably involved in the regulation of sugar transport.
Effects of rate of blood flow on fractional extraction and on uptake of infused noradrenaline by brown adipose tissue in vivo
Authors: Foster David O. , Depocas Florent , Zaror-Behrens Gloria , Frydman M. Lorraine , Lacelle Suzanne
Published: April 2011

The rate of blood flow (Q) to interscapular brown adipose tissue (IBAT) and the arteriovenous difference in plasma noradrenaline (NA) across the tissue were measured in warm-acclimated (WA) or cold-acclimated (CA) rats during infusion of NA at doses of 1–12.5 ng min−1 g−0.74 (approximately 0.2–2.7 μg min−1 kg−1) and in the period of steady calorigenic response associated with steady concentration of NA in arterial plasma (ANA). ANA was linearly related to the dose of NA. Calorigenic response, percentage of cardiac output to IBAT, and Q per gram of IBAT were sigmoid functions of ANA and at their maxima were about 2.5 times greater in CA than in WA rats. The rate of uptake of NA by IBAT increased with ANA and Q, each of which had a major influence on rate, but the coefficient of extraction of NA by the tissue (ENAIBAT) declined. Measurements in rats given a dose of propranolol that partially inhibited the NA-induced increase in Q to IBAT indicated that the decline in ENAIBAT was attributable primarily to the increase in Q rather than to increasing saturation of uptake mechanisms. Diffusion-limited extraction of NA is the probable basis for the effect of Q on ENAIBAT. Possible implications of flow-dependent extraction of NA in studies involving measurements of the uptake of exogenous NA by tissues or organs are discussed.
The dog common carotid artery: a sensitive bioassay for studying vasodilator effects of substance P and of kinins
Authors: Couture R. , Gaudreau P. , St-Pierre S. , Regoli D.
Published: April 2011

In order to develop a sensitive pharmacological preparation which would allow the measurement of the inhibitory effects of kinins and substance P (SP) in vascular smooth muscles, several large arteries of the dog were studied in vitro. The common carotid artery was found to be one of the most sensitive preparations to SP and kinins. When contracted with low concentrations of noradrenaline (between 3.0 × 10−8 and 3.0 × 10−7 M), this artery responds to SP (6.5 × 10−11 − 6.5 × 10−9 M) and bradykinin (BK) (8.1 × 10−11 − 9.1 × 10−8 M) with relaxations that are proportional to the concentrations of the two peptides. SP and BK appear to exert their relaxant effects through the activation of specific receptors as the exposure of the common carotid artery to concentrations of [Leu8]-angiotensin II, propranolol, methysergide, cimetidine, or atropine sufficient to inhibit the effects of the corresponding agonists do not affect the relaxing effect of SP and BK. [Leu8]-des-Arg9-BK (1.0 × 10−s M), indomethacin (2.8 × 10−5 M), and lioresal (4.7 × 10−5 M) are also inactive. When the dog common carotid artery is desensitized with high concentrations of SP, BK, eledoisin, and physalaemin a cross-desensitization is observed only between SP and physalaemin. These results support the conclusion that SP and kinins act on different receptors. The order of potency of kinins is the following: BK = [Tyr(Me)8]-BK > des-Arg9-BK, suggesting that the receptor for kinins is of the B2 type. The order of potency of peptides related to SP is SP > C-terminal 4-11 > C-terminal hexapeptide 6-11, similar to that observed in other vascular preparations.The results summarized in this paper indicate that the dog common carotid artery is a preparation sensitive to SP and BK and useful for studying the relaxant effect of these two peptides on vascular smooth muscles.
Erythrocyte life-span in dystrophic hamsters
Authors: Toffelmire E. B. , Boegman R. J.
Published: April 2011

[3H]Diisopropylfluorophosphate was used to label erythrocytes from normal and dystrophic hamsters. The mean erythrocyte life-span in dystrophic animals was 57.3 ± 1.6 days whereas in normal animals it was 50.1 ± 1.6 days.
Effect of vanadate on rat myometrium plasma membrane enzyme activities
Authors: Grover A. K. , Jones T. R. , Daniel E. E.
Published: April 2011

Vanadate inhibited K+-activated and K+-activated ouabain-sensitive p-nitrophenyl phosphatases of rat myometrium at nanomolar concentrations. The vanadate concentrations required for 50% inhibition were 220 ± 30 nM for the K+-activated component of this enzyme and 200 ± 30 nM for the K+-activated ouabain-sensitive component. Micromolar concentrations of vanadate inhibited acid and alkaline p-nitrophenyl phosphatases. ATP-dependent Ca uptake by the plasma membrane vesicles was not inhibited by 10 nM – 1 mM vanadate. Mg2+-ATPase was also not affected. Thus K+-activated and K+-activated ouabain-sensitive p-nitrophenyl phosphatase activities of the plasma membrane were most sensitive to inhibition by vanadate. Preliminary experiments demonstrated that similar to ouabain, vanadate inhibited potassium-induced abolition of spontaneous contractile activity of isolated rat myometrium in K-free Krebs. This effect of vanadate is consistent with vanadate inhibition of K+-activated ouabain-sensitive p-nitrophenyl phosphatase.
Effects of gestation and lactation on rat gastric fundus
Authors: Jolicoeur L. , Asselin J. , Morisset J.
Published: April 2011

This study evaluated the effects of gestation and lactation on stomach growth in rats. Constant increases were observed in gastric fundus weight during pregnancy and lactation, with a maximum obtained after 3 weeks of lactation. This increase in tissue weight was not associated with hyperplasia of the gastric fundus as in no instance did total DNA contents from mated females differ significantly from those of the unmated controls. Mild hypertrophy, as evidenced by significant increases in cellular mass and RNA and protein concentrations, was observed during late lactation. Gastrin might be responsible for these modest changes in the gastric fundus.
Peripheral vascular responses during acute anemia
Authors: Chapler C. K. , Stainsby W. N. , Lillie M. A.
Published: April 2011

Peripheral vascular responses during acute anemia were studied in 19 anesthetized dogs. In one study (n = 9) hindlimb weight and venous pressures were measured prior to and during acute anemia produced by isovolemic dextran-for-blood exchange. In another series of five control and five anemic dogs (hematocrit = 14 ± 1% (mean ± SE)), flow to the limb was occluded and arterial and venous pressure changes in the occluded limb were measured as an index of neurally mediated alterations in limb vasomotor tone. Following reduction of the hematocrit to 14 ± 0.3%, hindlimb weight decreased by an average of 10.0 g (P < 0.01) at 15 min and 12.8 g (P < 0.01) at 30 min of anemia. The decrease in limb weight was associated with a rise (P < 0.01) in limb venous pressure. There was also a relatively greater degree of vasomotor tone in the occluded hindlimb of anemic dogs as compared with control animals. Although both arterial and venous pressures decreased in an occluded hindlimb following the production of anemia, the decreases in vascular pressures were significantly less than those observed in control experiments. It was not possible to distinguish between tone changes in arteries and veins because of the presence of arteriovenous anastomoses. The data show that a peripheral-to-central blood volume translocation occurred in acute anemia which would increase venous return. Further, the results strongly suggest that the volume translocation was a result of an increase in venomotor tone.
Brain distribution and kinetics of desipramine in the rat
Authors: Hrdina P. D. , Dubas T. C.
Published: April 2011

Pharmacokinetics and regional as well as subcellular brain distribution of desipramine (DMI) were investigated in male rats after single and repeated intraperitoneal administration. After a single dose DMI enters brain rapidly, accumulates with increasing the dose, and attains concentrations about 20 times those seen in plasma. After repeated administration peak plasma and brain levels were 2.7 and 3.7 times, respectively, higher than after a single dose. No significant regional differences were found in brain distribution or disappearance half-lives of the drug. After chronic treatment the drug was preferentially retained in the P2 fraction of brain homogenate; this may reflect the critical portion of drug bound to sites responsible for its pharmacological action.
High-affinity uptake of choline in slices of rat cerebral cortex: effects of antidepressant and anticholinergic drugs
Authors: Jones R. S. G.
Published: April 2011

The high-affinity uptake of choline by rat cerebral cortical slices was inhibited by high concentrations (10–100 μM) of the tricyclic antidepressant drugs imipramine, desipramine, and iprindole in vitro. However the nontricyclic antidepressant viloxazine did not affect choline uptake even at a concentration of 1000 μM. None of the drugs had any effect on choline uptake by cortical slices when administered intraperitoneally (5, 10, 25 mg/kg) 30 min before sacrifice. Several anticholinergic drugs were tested for effects on in vitro uptake of choline. Hemicholinium-3 was a potent inhibitor of choline uptake but atropine, hexamethonium, and tubocurarine had no effect even at high concentrations (1000 μM).
The response of few-fiber carotid chemoreceptor preparations to almitrine in the dog
Authors: Bisgard Gerald E.
Published: April 2011

Almitrine, a long-lasting peripheral chemoreceptor stimulant, was given to nine dogs via intracarotid injection. Carotid chemoreceptor activity was recorded from single or few-fiber afferent nerve preparations. Doses of 10–20 μg/kg were generally sufficient to produce a brisk stimulatory response of less than 30 min duration. In four dogs decreasing arterial [Formula: see text] was found to allow a greater than additive response to almitrine. Infusions of NaHCO3 appeared to depress the response to almitrine whereas changing arterial [Formula: see text] had little effect on the carotid chemoreceptor response to almitrine. Neither dopamine infusion nor dopamine receptor blockade altered the responsiveness of the carotid chemoreceptors to almitrine.
Isometric contractile properties and instantaneous stiffness of amphibian skeletal muscle in the temperature range from 0 to 20 °C
Authors: Bressler Bernard H.
Published: April 2011

The isometric contractile properties of frog (Rana pipiens) and toad (Bufo bufo) sartorii have been studied over the temperature range from 0 to 20 °C. The isometric twitch tension was found to vary considerably between these two species and between muscles in the same species. Between 0 and 4 °C ther was very little change in maximum isometric twitch tension. Between 4 and 12 °C several muscles from frog or toad showed a potentiation of twitch tension whereas others showed a decline. Over this temperature range the toad sartorii consistently demonstrated a greater potentiation. By 12 °C a steady decline in twitch tension in both muscles was seen as the temperature approached 20 °C. The maximum isometric tetanic tension recorded between 18 and 20 °C increased fractionally to an average of 1.504 ± 0.029 (n = 4) for frog sartorii and to 1.377 ± 0.008 (n = 5) for toad sartorii. The time to peak twitch tension and the half-relaxation time decreased markedly with an increase in temperature. Moreover, the half-relaxation time was reduced by a greater proportion than the time to peak twitch tension. Measurements of instantaneous stiffness by controlled velocity releases from the plateau of isometric tetani revealed that the large increase in isometric tetanus tension as the muscle was warmed was not accompanied by a corresponding increase in the total number of active cross-bridges. The possibility that a decreased availability of intracellular Ca2+ ions at the contractile sites contributing to the fall of isometric twitch tension at elevated temperatures is discussed. The possibility exists that at elevated temperatures a change in the intrinsic-contractile ability of the muscle occurs which produces an increased tension per cross-bridge.
Early effects of glucose and oxygen deprivation on the spontaneous acetylcholine release from the myenteric plexus of the guinea pig ileum
Authors: Larson Roy E. , Martins Hilário R.
Published: April 2011

The early effects of glucose and oxygen deprivation on the spontaneous acetylcholine output from the myenteric plexus – longitudinal muscle preparation of the guinea pig ileum were studied using an incubation chamber that permitted rapid sample collection in 2-min intervals. Glucose deprivation or hypoxia resulted in a gradual decline in rate of spontaneous acetylcholine output. However, glucose deprivation plus hypoxia caused an acceleration in acetylcholine output within 10–15 min, which attained a rate seven times greater than observed under normal conditions. Recovery of low resting rates was obtained by reintroduction of oxygen and glucose into the bath medium. Neither morphine (2.7 × 10−5 M) nor tetrodotoxin (1.6 × 10−6 M) prevented the increase in acetylcholine output induced by energy deprivation. The substitution of Ca2+ by Mg2+, in the presence of EGTA, greatly reduced the acetylcholine output induced by energy deprivation. However, a small transitory output of acetylcholine was observed under these conditions which was resistant to tetrodoxin and not affected by depolarizing amounts of K+. The transitory output was repeatable by reintroduction of glucose and oxygen to the Ca2+-free medium with subsequent return to conditions of hypoxia and glucose deprivation.These results suggest that energy deprivation initially stimulates normal acetylcholine secretion by (a) increasing Ca2+ influx across the plasma membrane and (b) mobilizing an intracellular Ca2+ pool. This implies that processes involved in maintenance of normal low transmitter release are more sensitive to energy lack than the neurosecretion process itself.
Urinary zinc in relation to other cations and flow during volume expansion and intravenous chlorothiazide
Authors: Watkins Don W. , Antoniou Lucy D. , Shalhoub Robert J.
Published: April 2011

Urinary excretion of zinc, sodium, potassium, and calcium was studied in anesthetized dogs under conditions of volume expansion by saline infusion and volume expansion plus chlorothiazide administration. Zinc excretion was positively correlated to the fractional water excretion, as well as to the excretion of the other cations, during volume expansion. Chlorothiazide administration during volume expansion increased the zinc, sodium, and potassium excretion without changing that of calcium. The enhanced zinc excretion during chlorothiazide diuresis was equal to that expected on the basis of the increase in fractional water excretion alone. The urinary concentration of zinc appeared inversely related to the urine flow rate, reaching a minimum below that of the plasma ultrafilterable zinc concentration. The ratio of the clearance of zinc to that of sodium was 0.28, indicating a greater degree of net reabsorption for zinc than for calcium. These findings suggest that zinc and sodium reabsorption may be inhibited to a similar degree at chlorothiazide-sensitive sites in the tubule. Furthermore, the zinc reabsorptive mechanism seems capable of lowering urinary zinc concentration below that of ultrafiltrate and appears related in some way to sodium reabsorption.
Effect of oral propranolol on the anaerobic threshold and maximum exercise performance in normal man
Authors: Hughson Richard L. , MacFarlane Barbara J.
Published: April 2011

The effect of propranolol on the anaerobic threshold was studied in six healthy male volunteers. The subjects exercised on a cycle ergometer in a progressive exercise test to exhaustion with propranolol or no drug. Power output was increased by 30 W every 2 min. Propranolol caused a significant reduction of heart rate by 20–45 beats per minute at all power outputs. In light and moderate exercise, no differences in oxygen uptake, ventilation, or blood lactate were observed in the propranolol and no-drug tests. The anaerobic threshold was not different between the no-drug (2.32 ± 0.19 L O2/min, mean ± SD) and the propranolol (2.83 ± 0.27 L O2/min) tests; however, the heart rate at the anaerobic threshold was significantly lower in the propranolol (143 ± 13 beats per minute) than the no-drug (187 ± 9 beats per minute) tests. Above the anaerobic threshold, oxygen uptake was similar at a given power output but it reached a lower peak value (p < 0.02) in the propranolol (3.16 ± 0.16 L O2/min) versus the no-drug (3.64 ± 0.39 L O2/min) tests. It was concluded that propranolol caused no change in the anaerobic threshold in this specific progressive exercise protocol. The results suggest that a training intensity for endurance exercise based on the anaerobic threshold does not need to be modified for subjects on propranolol medication.
Antagonism of presynaptic adenosine receptors by theophylline 9-β-D-riboside and 8-phenyltheophylline
Authors: Clanachan A. S.
Published: April 2011

Theophylline 9-β-D-riboside and 8-phenyltheophylline were evaluated as presynaptic adenosine receptor antagonists in the rat vas deferens in vitro. Stimulation of presynaptic adenosine receptors, which results in an inhibition of the twitch response to electrical field stimulation, was achieved with 2-chloroadenosine, an adenosine analogue that appears not to be a substrate for the adenosine transport system. The presynaptic inhibitory action of 2-chloradenosine was antagonized by theophylline (10 and 100 μM) and by 8-phenyltheophylline (10 μM) but not by theophylline 9-β-D-riboside (100 μM). It is concluded that the addition of a ribose moiety to theophylline does not enhance the antagonist potency of the molecule but actually renders the compound inactive. However, 8-phenyltheophylline is approximately three times more potent than theophylline at presynaptic adenosine receptors.
Cardiovascular responses to intracisternal administration of nicotine in rats
Authors: Kubo Takao , Misu Yoshimi
Published: April 2011

The administration of nicotine into the cisterna magna evoked a delayed depressor effect with an initial pressor effect in anaesthetized rats. The depressor response was accompanied by a bradycardia. The cardiovascular effects of nicotine were abolished after intracisternal administration of hexamethonium but not after atropine given via the same route. Intravenous administration of methylatropine abolished the bradycardic response to nicotine but did not affect the blood pressure responses. The pressor effect of nicotine was abolished by intravenous administration of phenoxybenzamine. The cardiovascular effects of nicotine injected intracisternally were abolished when the diffusion of nicotine onto an area around the area postrema was interrupted using a polyethylene tube. In contrast, nicotine applied to the area produced a marked pressor–depressor response. It is concluded that the cardiovascular responses to intracisternal administration of nicotine result from the activaiton of central nicotinic receptor sites that may be present around the area postrema.
The effect of 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene on caffeine-induced contractures of skeletal muscle
Authors: Rahwan Ralf G. , Gerald Michael C.
Published: April 2011

It has been previously postulated that 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene (pr-MDI) exhibits calcium antagonistic properties with an intracellular site of action. The present investigation further substantiates this hypothesis by providing evidence that pr-MDI inhibits caffeine-induced contractures (which are mediated by intracellular calcium) of the isolated rat hemidiaphragm skeletal muscle both in the presence and in the absence of extracellular calcium.
Evidence for pattern generator control of the effects of spindle afferent input during rhythmical jaw movements
Authors: Goldberg Louis J. , Chandler Scott H.
Published: April 2011

The following recordings were made during spontaneous rhythmic jaw movements in the anesthetized guinea pig: jaw movement in the vertical plane, electromyograms from the digastric muscle (a jaw opener), and intracellular recordings from motoneurons and spindle afferent fibers of the jaw-closer muscles.The rapid jaw-opening phase of these rhythmic movements is characterized by a marked increase in activity in the spindle afferent fibers of the jaw-closer muscles and a coincident pronounced hyperpolarization of the membranes of the jaw-closer motoneurons.It is proposed that the excitatory spindle afferent input evoked by passive stretch of the jaw-closer muscles resulting from a centrally programmed contraction of the jaw-opener muscles impinges upon closer motoneurons that have been hyperpolarized as part of the central program. The hyperpolarization inhibits the motoneurons and nullifies the effect of the spindle afferent input thereby assuring relaxation of the closer muscles and an unimpeded rapid jaw-opening movement.
The mechanism of the bronchoconstriction induced by unilateral orthodromic stimulation of the carotid sinus nerves
Authors: Biggs D. F. , Peterson M. A.
Published: April 2011

Unilateral stimulation of carotid sinus nerve afférents at 2 and 4 V produced pulse duration-dependent reflex bronchoconstriction which was unaffected by midcervical, bilateral vagotomy. The bronchoconstriction consisted of two pharmacologically distinct components. One component was blocked by atropine or atropine methiodide, the other was blocked by either mepyramine or disodium cromoglycate. Combinations of atropine or atropine methiodide with mepyramine or disodium cromoglycate completely eliminated bronchoconstrictor responses to nerve stimulation. These data indicate that two separate bronchoconstrictor reflexes, possibly resembling serotonin- and diazoxide-induced reflex bronchoconstnction are activated by stimulation of afferent fibers in the carotid sinus nerves.
Fetal and maternal estrogen concentrations throughout pregnancy in the sheep
Authors: Challis John R. G. , Patrick John E.
Published: April 2011

Because of the possible importance of estrogens in events of early pregnancy, and in fetal lung maturation and parturition, we have measured unconjugated estrone (E1) and estradiol (E2) concentrations in amniotic fluid (AF) and allantoic fluid (ALF) from pregnant sheep, and have compared these values with estrogen concentrations in the fetal and maternal plasma. Samples were collected under acute conditions of general anaesthesia or from chronically catheterized animals during late pregnancy. E1 always exceeded E2 in AF and ALF. On days 100 to term, the concentrations of E1 sulphate in AF and ALF greatly exceeded those of E1 but decreased towards term. E1 was elevated in AF on day 50, decreased to day 100, and in chronic preparations increased significantly before birth, at the time of the prepartum rise in E1 in maternal and fetal plasma. E1 in ALF was higher than in AF on days 50 and 100, but no consistent pattern of E1 in ALF with gestation was established, due in part to substantial interanimal variation. Similar concentrations of E2 were found in AF and ALF. In AF, E2 rose significantly before birth, with a similar time course to the prepartum rise in E2 in maternal and fetal plasma. In early pregnancy, the ratio E1/E2 in umbilical cord blood was higher than in all other compartments. We conclude (1) there is evidence for estrogen production in early pregnancy (day 50), favouring E1; (2) E1 predominates over E2 in the fetal as well as maternal compartment, although its concentration in amniotic and allantoic fluid is substantially less than E1S; (3) parturition is preceeded by rising concentrations of E1 and E2 in AF as well as in maternal and fetal plasma; and (4) this increase probably reflects rising fetoplacental production and may indicate increasing estrogen availability to the fetal membranes, uterine and fetal tissues around the time of birth.
Prolonged inhibition of pressor response to vasopressin by a potent specific antagonist, [1-(β-mercapto-β,β-cyclopentamethylenepropionic acid) 2-(O-methyl)tyrosine]arginine-vasopressin
Authors: Pang Catherine C. Y. , Leighton Kenneth M.
Published: April 2011

The specificity, the potency, and the duration of action of [1-(β-mercapto-β,β-cyclopentamethylenepropionic acid) 2-(O-methyl)tyrosine]arginine-vasopressin [d(CH2)5Tyr(Me)AVP] to antagonize pressor responses to arginine vasopressin (AVP) was examined in pentobarbital-anaesthetized rats. Injection of the compound (4 μg∙kg−1 i.v.) prevented pressor responses to i.v. infusions of supramaximal doses of AVP, but not to i.v. infusions of another peptide, angiotensin II (Ag II). The antagonism of AVP persisted for at least 3 h. Since i.v. injection of the compound in the absence of exogenous administration of AVP did not cause any change in the arterial pressure of rats, it appears that the compound is devoid of agonistic pressor activity. The results show that d(CH2)5Tyr(Me)AVP is a potent and a specific antagonist of pressor responses to AVP.
Evaluation of surgical denervation of the liver in cats
Authors: Lautt W. Wayne
Published: April 2011

Bilateral carotid arterial occlusion was used as a means of reflexly activating hepatic sympathetic nerves in cats anesthetized with pentobarbital. The resultant hepatic arterial constriction was used as an index of effective surgical denervation of the liver in situations where the hepatic arterial blood pressure was held constant or was allowed to rise parallel with the systemic blood pressure. Cutting the anterior nerve plexus (around the common hepatic artery) produced a highly variable but incomplete reduction in the constrictor response to carotid occlusion. The remainder of the constrictor effect was abolished only when the posterior plexus and hepatic ligaments were also cut. Thus, vascular resistance in the hepatic artery is controlled by both the anterior and posterior hepatic plexuses but the contribution of each plexus varies considerably from animal to animal. This must be considered in any experiments that use, or have used, denervation or stimulation of the hepatic nerves.
Relative sensitivity of the canine sines node and atrioventricular node to acetylcholine
Authors: Musgrave G. E. , Branch C. E. , Beckett S. D.
Published: April 2011

This study was undertaken to evaluate the relative sensitivity of the canine sinus and atrioventricular (AV) nodes to acetylcholine (Ach). A dose-dependent increase in both A–A and R–R intervals occurred when Ach (5–320 μg/kg) was injected into the left ventricle of both conscious and anesthetized dogs. Comparison of the ED50 values for Ach (derived by weighted nonlinear least squares regression analysis of the dose-dependent changes in the A–A and R–R intervals) revealed the AV node to be 1.9-fold more sensitive to the effect of Ach than the sinus node in the conscious dogs and 3.3-fold more sensitive than the sinus node in the anesthetized group. The results imply that the greater sensitivity of the AV node to Ach is, at least in part, responsible for the occasional second degree block commonly observed in clinically normal dogs.
Tetrodotoxin-resistant release of ATP from guinea-pig taenia coli and vas deferens during electrical field stimulation in the presence of luciferin-luciferase
Authors: White Thomas , Potter Pamela , Moody Catherine , Burnstock Geoffrey
Published: April 2011

Guinea-pig taenia coli was superfused with medium containing luciferin-luciferase at 25 °C in order to directly detect the release of ATP. The resting lone of the tissue increased during the first 2–10 min of superfusion and then fell to a low level where spontaneous activity ceased. Under high tone conditions during the first 2–10 min of exposure to luciferin-luciferase, in the presence of atropine and guanethidine, ATP was released and the taenia coli relaxed when stimulated at 2–4 Hz, 70 V, 0.3-ms pulses for 15 s. Variable and continuous changes of tone made it difficult to test whether relaxation and release of ATP were tetrodotoxin sensitive. Field stimulation of preparations showing low tone after the initial exposure to luciferin-luciferase also resulted in ATP release. The muscle usually contracted during stimulation, even in the presence of atropine. Release was not due to movement of the muscle, since the release preceded the movement of the tissue and contraction with acetylcholine failed to release ATP. Neither release nor the contractile response of the tissue were blocked by tetrodotoxin (3 × 10−6 M), suggesting that under these conditions the release of ATP originated from the muscle or possibly directly from nerve terminals. A qualitatively similar release of ATP was also observed when desheathed guinea-pig vas deferens was field-stimulated electrically in the presence of luciferin-luciferase. Tetrodotoxin did not block ATP from this tissue either, but unlike the taenia coli, it did abolish the contractile response, which was not affected by luciferin-luciferase during the 1st h of exposure. It is concluded that in the presence of luciferin-luciferase the field-stimulation induced release of ATP observed in guinea pig taenia coli or vas deferens was not mediated by propagation of action potentials in nerve.
Adrenergic activity in arteries of spontaneously hypertensive rats
Authors: Zsotér Thomas T. , Sirko Steve , Wolchinsky Camille , Kadar Dezso , Endrenyi Laszlo
Published: April 2011

This study compares the uptake and release of [3H]norepinephrine and residual 3H content in the tail artery of 7- to 9-week-old and 16- to 18-week-old spontaneously hypertensive rats (SHR) and age matched normotensive Wistar Kyoto rats (WKR). The composition of the 3H overflow from the artery, analyzed with column chromatography, revealed similar proportion of norepinephrine and in metabolites, namely normetanephrine, O-methylated deaminated products, dihydroxy-phenylglycol, and dihydroxymandelic acid in SHR and WKR. [3H]Norepinephrine was retained however in greater proportion in vessels of young and older SHR than in WKR.
Phenothiazines inhibit adenosine uptake by rat brain synaptosomes
Authors: Phillls J. W. , Wu P. H.
Published: April 2011

Phenothiazine (chlolpromazine, trifluoperazine, thioridazine, and fluphenazine) are potent inhibitors of the rapid uptake of adenosine by rat cerebral cortical synaptosomes. Other antipsychotics with fewer sedative side effects (clozapine, pimozide, haloperidol) were weaker inhibitors of adenosine uptake. It is hypothesized that inhibition of adenosine uptake is a significant factor in the sedative, antianxiety, and analgesic actions of the phenothiazines.
Thallous ion activation of p-nitrophenylphosphatase of rat myometrium plasma membrane
Authors: Grover A. K. , Frederickson M. , Daniel E. E.
Published: April 2011

Addition of thallous ion (Tl+) inhibited the spontaneous mechanical activity of rat myometrium in K-free Krebs solution with an I50 value of 30 μM. The corresponding value for I50 for similar inhibition by addition of K+ was 150 μM. Tl+ as well as K+-activated p-nitrophenylphosphatase (PNPPase) of isolated rat myometrium plasma membrane vesicles. Half maximal activation was caused by 0.47 mM Tl+ or 1.6 mM K+. Maximal enzyme activities obtained using Tl+ and K+ were comparable. The Km values for the substrate p-nitrophenylphosphate using Tl+ (1.24 mM) and K+ (1.46 mM) were also similar. Activation by either ion was inhibited by ouabain, Na+, inorganic phosphate, and vanadate (V + 5). The results suggest that Tl+ can substitute for K+ for activation of the Na–K pump of rat myometrium plasma membrane.
Catecholamines and the cephalic phase of gastric secretion
Authors: Etzel K. , Wisecarver J. , Magee D. F.
Published: April 2011

Methoxamine, an α-adrenergic agent, and isoproterenol, a β-adrenergic agent, significantly augmented indirect vagally stimulated (intravenous 2-deoxy-D-glucose) acid and pepsin secretion from the main stomachs of conscious dogs. Heidenhain pouch secretion in the same dogs was unaffected.
The influence of "nonmyoplasmic" sodium on the measured value of the sodium efflux from barnacle muscle
Authors: Menard M. R. , Hinke J. A. M.
Published: April 2011

In single striated muscle cells of the giant barnacle Balanus nubilus, the sodium content of the myoplasm was measured with an intracellular microelectrode, and the total sodium content of the cell was measured by flame photometry, during immersion of the cells in sodium-free solution. The sodium content of the myoplasm declined slowly but steadily from ca. 10 mmol/kg water to ca. 4 mmol/kg water during immersions lasting up to 16 h. The "nonmyoplasmic" sodium content of the cells, defined as the sodium content after subtraction of the sodium in the extracellular (sorbitol) space and in the myoplasm, declined rapidly from ca. 15 mmol/kg water to ca. 3 mmol/kg water during the first 30 min of immersion in sodium-free solution, but remained constant thereafter. The rapidly lost portion of the nonmyoplasmic sodium (ca. 12 mmol/kg water) was ascribed to the extracellular space but the location of the inexchangeable portion was not discovered. The behavior of the efflux of 22Na which was loaded into the myoplasm by microinjection was consistent with this interpretation. It was concluded that the nonmyoplasmic sodium does not have an appreciable influence on the measured value of the sodium efflux from the myoplasm of barnacle muscle cells.
Epicardial coronary venous pressure
Authors: Armour J. A. , Klassen G. A.
Published: April 2011

Coronary venous pressure was measured in two sites in the canine heart. Central coronary venous pressure was that pressure recorded by a catheter in an epicardial coronary vein directed antegrade towards the coronary sinus. This pressure was 6 ± 1/0.2 ± 0.6 mmHg (1 mmHg = 133.322 Pa). Peripheral coronary venous pressure was recorded by a catheter in an epicardial vein which was directed towards the apex. It was 27 ± 5/8 ± 2 mmHg. Simultaneous measurement of peripheral coronary artery and vein pressures demonstrated similar pressure wave forms with peak pressures during systole. Peripheral coronary venous pressure was similar if measured from a side branch leading to the major epicardial veins or via a catheter placed retrograde in a major epicardial vein. Thus artifact of measurement caused by antegrade catheter placement was negligible. During norepinephrine administration, venous pressures were significantly increased. These data suggest that coronary venous pressures are higher than is generally assumed and that intramyocardial pressure has an important effect upon coronary venous pressure.
Sedimentation characteristics of noradrenergic vesicles from rat interscapular brown adipose tissue
Authors: Zaror-Behrens Gloria , Depocas Florent , Lacelle Suzanne
Published: April 2011

Rat interscapular brown adipose tissue (IBAT) was homogenized to release the noradrenergic vesicles present in its dense sympathetic innervation. The vesicles were then studied by several sedimentation techniques using noradrenaline (NA) and dopamine β-hydroxylase (DBH) as markers. Sixty-three percent of the DBH activity and 29% of the NA in homogenates (0.25 M sucrose, 5 mM Tris, pH 7.4 at 21 °C) of IBAT from 28 °C acclimated rats sedimented in the microsomal fraction (226 600 × gmax, 60 min). Differential sedimentation of the microparticulate DBH in a low-speed supernatant fraction of the homogenate indicated at least two distinct populations of microparticles with average sedimentation coefficients of 80 ± 11 and [Formula: see text] (4 °C) and containing, respectively, about 65 and 35% of the sedimentable DBH. Upon isopycnic, sucrose density centrifugation of the resuspended microsomal fraction, DBH peaked at a density of 1.091 but extended as a broad shoulder up to a density of about 1.19. During rate zonal centrifugation of the resuspended microsomal fraction on sucrose density gradients, microparticulate DBH and NA separated into slow and fast moving components. The modal density of the slow moving component upon isopycnic recentrifugation was 1.092, while the fast moving one, similarly treated, became almost equally distributed over a range of densities from 1.12 to 1.19. For the slow moving component, NA and DBH relative to protein were, respectively, 6.5 and 23 times more concentrated than in the IBAT homogenate. On the basis of its measured sedimentation characteristics, the slow moving component would correspond to vesicles having a calculted diameter of 66 nm. The data thus indicate that in IBAT, DBH and NA can be separated into two distinct populations of sedimentable particles. Whether or not these correspond to the small and large dense-cored vesicles observed by ultramicroscopy of IBAT remains to be demonstrated.
Vasodilator actions of several N-nitroso compounds
Authors: Lippton Howard L. , Gruetter Carl A. , Ignarro Louis J. , Meyer Richard L. , Kadowitz Philip J.
Published: April 2011

Recent studies have shown that N-nitroso compounds can activate arterial guanylate cyclase and relax isolated arterial smooth muscle; however, the effects of these substances on the cardiovascular system in the anesthetized cat are unknown. The present study was undertaken to compare the effects of several nitrosoguanidines and a nitrosamine, N-nitrosodimethylamine, on arterial guanylate cyclase activity, isolated arterial smooth muscle tone, and systemic vascular resistance in the anesthetized cat. Intravenous injections and infusions of the nitrosoguanidines glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) decreased systemic arterial pressure. During intravenous infusion of the nitrosoguanidines GTN and SNP, cardiac output was unchanged at the peak of the decrease in aortic pressure, indicating that the nitrosoguanidines GTN and SNP both reduced systemic vascular resistance. In addition, intraarterial injections of the nitrosoguanidines produced dose-dependent decreases in perfusion pressure in the feline mesenteric vascular bed perfused at constant flow. These substances were potent relaxants of isolated arterial smooth muscle and markedly activated arterial guanylate cyclase. In contrast, N-nitrosodimethylamine was devoid of vasodilator activity in vivo and exerted only minimal effects on isolated arterial smooth muscle tone or on arterial guanylate cyclase activity. The present data demonstrate a relationship between guanylate cyclase activation and arterial smooth muscle relaxation and suggest that the vasodilator effects on resistance vessels in vivo in response to selected N-nitroso compounds may involve such a mechanism. Although the significance of the presently reported cardiovascular responses to N-nitroso compounds is uncertain, N-nitroso compounds may represent a previously unrecognized class of substances which can be formed in the body and which possess marked vasodilator activity. It is possible that this vasodilator activity may involve the relaxation of vascular smooth muscle through activation of guanylate cyclase.