bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of intramuscular pH oscillations in the isolated perfused rat heart by different interventions
Authors: Yates J. C. , Kleinberg I. , Khatter J. C. , Hoeschen R. J. , Das P. K. , Dhalla N. S.
Published: April 2011

Changes in the intramuscular pH oscillations were examined by the use of an antimony electrode upon perfusing the isolated rat heart under different experimental conditions. The pH oscillations were decreased upon perfusing the hearts with Na+- or Ca2+-free medium and increased upon perfusing with K+-free medium. Increasing the temperature of perfusion medium from 25 to 40 °C or omitting glucose from the perfusing medium decreased the magnitude of oscillations. On the other hand, complete interruption of the perfusion flow resulted in an increase in the amplitude of pH oscillation. An initial increase followed by a decrease in the pH oscillation was seen when hearts were perfused with medium containing lactic acid at pH 6.6. These results suggest that pH oscillations reflect fluctuations in myocardial metabolism.
Intracellular divalent cations and neuronal excitability
Authors: Krnjević K. , Lamour Y. , MacDonald J. F. , Nistri A. , Puil E. , Werman R.
Published: April 2011

Intracellular injections of Mg into cat spinal motoneurones have a depolarizing action, associated with a fall in input conductance, and depression of the postspike hyperpolarizing after-potential (a.h.p.) as well as its underlying conductance increase. There is also an increase in excitability, sometimes leading to outright discharge, and a change in the current–firing relation: the normal primary range is largely abolished and the firing appears to have the characteristics of the normal secondary range. Intracellular effects of Mg are thus mainly opposite to those of Ca, possibly owing to competition at sites where Ca activates K channels. Intracellular injections of Mn also tend to depress the a.h.p. but have relatively little effect on resting potential and conductance, or action potentials. Co also depresses the a.h.p. but has a more pronounced depolarizing action, and produces particularly strong depression of action potentials. By contrast intracellular Sr tends to raise the membrane conductance and has a mild hyperpolarizing effect. During the injection of Sr, a.h.p's are depressed but this is followed by a rebound of increased a.h.p. amplitude and conductance. Unlike the other divalent cations tested, Sr strongly depressed excitatory postsynaptic potentials. In most respects Sr appears to behave like Ca.
Distribution and metabolism of adrenocorticotropin in the rat
Authors: Normand Maurice , Lalonde Josee
Published: April 2011

The time course of plasma bioactive adrenocorticotropin (ACTH) concentrations measured following two rapid injections of the hormone at doses of 7.5 and 22.5 mU/100 g, iv, and one infusion over a period of 80 min at a rate of 1.3 mU/min per 100 g, to male Sprague–Dawley rats whose endogenous release of ACTH had been blocked, leads to the conclusion that the hormone is distributed in two compartments. Indeed, the rapid fall of plasma ACTH concentrations in the early minutes following either the injections or the stop of the infusion is followed by a much slower phase. There is no significant difference between the measurements and the two-compartment model outputs. The model represents, on the average, the mean values of the measurements plus or minus 1 standard error for the single injections and plus or minus 1.2 standard error for the infusion.
The role of the cholinergic systems in the central control of thermoregulation in rats
Authors: Lin M. T. , Chen F. F. , Chern Y. F. , Fung T. C.
Published: April 2011

Systemic and central administration of methacholine (a synthetic choline derivative) both produced dose-dependent decreases in rectal temperature in rats at all the ambient temperatures studied. Both at room temperature (22 °C) and in the cold (8 °C), the hypothermia in response to methacholine application was brought about by both a decrease in metabolic heat production and an increase in cutaneous circulation. In the heat (29 °C), the hypothermia was due solely to an increase in respiratory evaporative heat loss. Furthermore, the methacholine-induced hypothermia was antagonized by central pretreatment of atropine (a selective blocker of cholinergic receptors), but not by the central administration of either 6-hydroxy-dopamine (a relative depletor of catecholaminergic nerve fibers) or 5,6-dihydroxytryptamine (predominately a serotonin depletor). The data indicate that activation of the cholinergic receptors within brain with methacholine decreases heat production and (or) increases heat loss which leads to hypothermia in rats.
Modes of rouleaux formation of human red blood cells in polyvinylpyrrolidone and dextran solutions
Authors: Sewchand Lionel S. , Canham Peter B.
Published: April 2011

The mechanics by which normal human erythrocytes join on a plastic cover slip into two cell doublets and larger aggregates of rouleaux were studied microscopically. Polyvinylpyrrolidone (PVP-360) or dextran (DX-70 or DX-110) were used as the rouleau agents. The minimum concentration of the rouleau-inducing agents required to form doublets was 1 g/L for PVP-360 and 5 g/L for the DXs. Three modes of interaction were observed in Ringer's solution with PVP or DX, cresting and flipping (involving no intercellular sliding) and a sliding mode of doublet formation (involving less gravitational work and less cellular deformation). The sliding mechanism occurred in suspensions with the lower concentrations of the rouleau agent but was also observed when geometric constraints prevented the nonsliding interaction of larger groups of cells in the higher concentrations of the rouleau agent. The technique provides a sensitive index for studying the combined effect of cellular flexibility and intercellular adhesion. Significant changes were observed for reduced membrane surface charge or reduced ionic calcium.
Effect of cholecystokinin, secretin, and gastric inhibitory polypeptide on insulin release from the isolated perfused rat pancreas
Authors: Pederson Raymond A. , Brown John C.
Published: April 2011

The actions of gastric inhibitory polypeptide (GIP) on insulin release from the isolated perfused rat pancreas were compared with those of pure secretin and cholecystokinin (CCK). At dose levels physiologically achievable for GIP (1 ng/mL perfusate), infusions of CCK stimulated significant insulin release both on a weight (1 ng/mL) and a molar (770 pg/mL) basis. Although 50% as potent as GIP on a weight basis and 43% as potent on a molar basis, the insulin response to CCK was multiphasic and sustained for the duration of the infusion. The action of CCK, like that of GIP, was glucose dependent yielding no significant insulin release at a low perfusate glucose concentration (80 mg/dL). Irrespective of perfusate glucose concentration or dose (1 or 5 ng/mL), secretin failed to stimulate significant release of insulin from the perfused pancreas. It was concluded that secretin is ineffective as an incretin and that a physiological role for CCK in an enteroinsular axis awaits accurate measurement of circulating levels of immunoreactive CCK.
Ca2+ utilization in guinea pig ileal longitudinal smooth muscle in response to a series of muscarinic agonists
Authors: Rosenberger L. B. , Triggle D. J.
Published: April 2011

45Ca uptake associated with the mechanical responses to a series of muscarinic agonists including carbachol, cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide, and three related 1,3-dioxolanes, including full and partial agonists, has been measured. Generally good agreement is found between the dose–response curves for 45Ca uptake and mechanical response, indicating that the processes of 45Ca entry, believed to be mediated through Ca2+ channels, and contractile response are closely linked. Consistent with this, partial agonists show (relative to full agonists) a reduced 45Ca uptake. The dose–response curves for carbachol-mediated contractile response and 45Ca uptake are compared with available literature data for carbachol action in the guinea pig ileal smooth muscle including binding, depolarization, and phosphatidylinositol turnover.
Cholesterol turnover in miniature swine with a portacaval shunt
Authors: Huang Yung-Sheng , Lussier-Cacan Suzanne , Bidallier Maurice , Tsay Liang-Huei , Rheault Marcel J. , Davignon Jean
Published: April 2011

Plasma cholesterol turnover was studied in sham-operated and portacaval-shunted miniature swine following an intravenous injection of labeled cholesterol. The specific radioactivity – time curves for periods of 6–7 weeks and 11–13 weeks were analyzed in both groups by a digital computer according to a two-pool and a three-pool model. In this study, the three-pool model generally provided a better fit to the observed data than did the two-pool model. The half-lives of the first and second exponents were significantly decreased in the shunted animals, indicating an elevated turnover of cholesterol. It is suggested that increased hepatic degradation of cholesterol was responsible for the hypocholesterolemic effect of the shunt in our study.
Comparison of pharmacological effect of adiphenine and physiological stimulation by luteinizing hormone releasing hormone on luteinizing hormone release by rat anterior pituitaries in vitro
Authors: Fevre M. , Jordan D. , Tourniaire J. , Mornex R.
Published: April 2011

The mechanism of action of adiphenine on in vitro rat anterior pituitary LH release was studied and compared with that of the physiological stimulator luteinizing hormone releasing hormone (LH-RH) on LH release. The comparative study showed that adiphenine and LH-RH were able to increase medium LH concentration in a dose-dependent manner and had similar time courses of action between 1 and 4 h incubation. However, there were several main differences between the effects of adiphenine and LH-RH. The adiphenine action was not calcium dependent, was inhibited in a high K+ medium concentration, and was substituted after energy depression. It is concluded that adiphenine probably acts near the ultimate steps of the LH release pathway and could be a useful pharmacological tool for studying the mechanism of LH release.
In vitro response of enzyme-dispersed rat intestinal villus and crypt cells to hormones
Authors: Hoffman Alan G. D. , Kuksis Arnis
Published: April 2011

Villus and crypt cells isolated from rat jejunal tissue by an improved enzymatic procedure were tested for their ability to respond to hormonal stimulation using several metabolic tracers. Incubation with cyclic AMP, theophylline, isoproterenol, and epinephrine resulted in 20–70% increases in incorporation of D-glucosamine into glycoproteins. The newly formed material was largely (90–95%) recovered from the medium, apparently as a result of active secretion, because tests for cellular leakage and breakage failed to account for it. The above hormones and pharmacological agents as well as glucagon, insulin, and Cortisol, however, failed to modify the rate of incorporation of acetate and glucose into the total cellular lipids of the isolated crypt and villus cells. Likewise, segments of intestinal tissue, although readily responding with increased incorporation of D-glucosamine (50–100%), failed to demonstrate any effect of added hormones on the incorporation of acetate even when lipogenesis was stimulated by addition of glucose or fructose. These findings are in agreement with certain previous studies with intact intestinal tissue in vivo and in vitro, and attest to the suitability of the enzyme-dispersed cells for metabolic studies.
Verapamil-induced changes of muscle culture acetylcholinesterase
Authors: Patterson Gary T. , Cisson C. Michael , Entrikin Richard K. , Wilson Barry W.
Published: April 2011

Pectoral muscle of 11-day-old normal chick embryos was cultured for 7 days and then treated with verapamil for up to 48 h to test the hypothesis that verapamil affects acetylcholinesterase (ACHE) activity. Cellular ACHE activity increased, activity released into the medium decreased, and net activity decreased with increasing concentrations of verapamil up to 30 μg/mL. Neither protein synthesis nor total cell protein content changed with concentrations of 1–30 μg of verapamil/mL. One hundred micrograms of verapamil per millilitre was toxic to cultures. To determine the effect of verapamil on newly synthesized ACHE, 30 μg of it per millilitre was added to cells treated with diisopropylphosphorofluoridate (DFP). During recovery from DFP, the amount of newly synthesized ACHE released into the medium was increased threefold. Cellular leucine incorporation, total cell protein, and creatine phosphokinase activity were unaffected by the presence of verapamil during cellular recovery from DFP. The results indicate that verapamil has a direct effect on skeletal muscle cells by specifically decreasing net synthesis of ACHE and (or) inhibiting its release from the cell.
Structure–activity studies on substance P
Authors: Couture R. , Fournier A. , Magnan J. , St-Pierre S. , Regoli D.
Published: April 2011

A complete series of analogues of substance P (SP) in which L-Ala was used to replace the natural residues one by one, and the C-terminal free acid SP, were synthesized and tested in order to study the relationships between chemical structure and biological activities. All compounds were tested for their hypotensive effect on the rat blood pressure and for their myotropic activities on the guinea pig ileum, the rabbit anterior mesenteric vein, and the rat vas deferens.The results indicate that the first five residues from the amino end and Gly9 can be replaced by L-Ala without change of hypotensive or myotropic activities, but the substitution of the residues from the carboxyl end (Met11, Leu10, Phe8, and Phe7) with L-Ala brings about variable losses of affinity. All analogues maintain full intrinsic activity in the guinea pig ileum; [Ala10]-SP and [Ala11]-SP maintain more than 80% of intrinsic activity in the mesenteric vein, the other analogues being full agonists; moreover, [Ala7]-SP and [Ala 8]-SP show a weaker hypotensive potency than all other compounds. The effect of SP is not modified by an inhibitor of the converting enzyme (YS 980), but that of SP free acid is either potentiated (rabbit mesenteric vein, rat vas deferens) or not modified (rat blood pressure, guinea pig ileum).The findings presented in this paper are discussed in terms of structure–activity relationships. However, no clear indication has emerged as to the identity of the active group(s) or on a possible distinction between the molecular sequences or groups involved in binding or in stimulation of receptors by SP.
Inhibition of neuronal noradrenaline uptake by angiotensin II in the rat mesentery
Authors: Jackson Edwin K. , Campbell William B.
Published: April 2011

In the isolated perfused rat mesentery, angiotensin II (3 × 10−9 M) in subpressor doses enhanced the vasoconstrictor responses to noradrenaline by 9.6 ± 1.4 mmHg. However, in mesenteries obtained from rats chemically sympathectomized with 6-hydroxydopamine, angiotensin II was without effect. Treatment of mesenteries with the noradrenaline neuronal uptake blockers desmethylimipramine (10−10 M), protriptyline (10−10 M), or cocaine (10−6 M) potentiated responses to noradrenaline by 3.8 ± 0.84, 3.7 ± 0.67, and 5.5 ± 0.26 mmHg, respectively. Angiotensin II alone or in combination with either desmethylimipramine, protriptyline, or cocaine potentiated the noradrenaline responses to a similar extent. On the other hand, corticosterone (1.5 × 10−6 M), an extraneuronal uptake blocker, enhanced noradrenaline responses by 4.3 ± 1.4 mmHg, and this enhancement was additive with the potentiation produced by cocaine and (or) angiotensin II. We conclude that angiotensin II in subpressor doses acts presynaptically to block selectively the neuronal uptake of noradrenaline without any appreciable effect on extraneuronal uptake.
Recent studies of the actions of cholinomimetic drugs on adrenergic nerves and their implications for the cholinergic link hypothesis
Authors: Jayasundar S. , Vohra M. M.
Published: April 2011

This review analyzes the results of recent studies of the actions of cholinomimetic drugs on adrenergic nerve terminals and their implications for the cholinergic link hypothesis. Thus far, evidence suggests that the only possible action of endogenous acetylcholine (ACh) present near noradrenaline (NA) stores is an inhibition of the release of NA from the adrenergic nerve terminals and that NA is released only when the action of acetylcholinesterase in inhibited. Nicotinic agents have been shown to act on adrenergic nerve terminal membranes, a finding that casts doubt on the proposed intraneuronal cholinergic sites for the action of endogenous ACh. Evidence also indicates that the mode of adrenergic neurone blocking action of bretylium and guanethidine is independent of the proposed cholinergic process in NA release. Current findings do not support the proposal that nicotinic agents in higher concentrations interfere with adrenergic neurotransmission. It is therefore concluded that nicotinic agents, in causing the release of NA from adrenergic nerve terminals, are merely exhibiting a pharmacological action and not mimicking the physiological function of ACh, as proposed by the cholinergic link hypothesis.
Antipyrine metabolism in man: simultaneous determination of norantipyrine and 4-hydroxyantipyrine in urine by gas chromatography
Authors: Inaba T. , Fischer N. E.
Published: April 2011

A gas chromatographic method was developed to determine metabolites of antipyrine, norantipyrine (NORA), and 4-hydroxyantipyrine in urine using p-methylated NORA as internal standard. This method requires no derivatization and has ample sensitivity to determine these metabolites in urine after ingestion of antipyrine, a compound widely used as a hepatic probe of drug oxidation.
Effects of fasting on the diuretic response and disposition of furosemide in rats
Authors: Chakrabarti Saroj K. , Brodeur Jules
Published: April 2011

The influence of fasting on the relationship between the disposition and diuretic effect of furosemide was studied in rats. Fasting consisted of withholding solid food, but not water, for a period of 16 h before administering furosemide (10 mg/kg, sc) or a saline vehicle. Normally fed animals also received furosemide or the vehicle. Fasting did not modify the diuretic or the natriuretic effect (per 100 g body weight) of furosemide. The distribution of total furosemide in plasma or tissues was not affected by fasting. On the other hand, fasting which produced increasing amounts of endogenous free fatty acids in plasma and kidneys increased the concentration of free furosemide in fasting plasma but not in fasting kidney or liver of rats. The in vitro binding constant of furosemide to physiological concentrations of plasma proteins was decreased from the control value by a factor of 6.5 as a result of fasting. Neither unchanged furosemide nor its metabolite in the urine was affected by fasting. Incubation of kidney cortex tissue slices with furosemide both in the presence and absence of free fatty acid indicated an inhibition of furosemide uptake in a manner closely parallel to inhibition by probenecid. Thus, failure to observe a more pronounced diuretic and saluretic effects of furosemide in fasted rats, in spite of higher concentration of free plasma furosemide, might be due to the inhibitory effect of endogenous free fatty acids and (or) other endogenous substances on the uptake of furosemide by renal tubular cells although some homeostatic control mechanisms related to fasting could also be involved.
The effects of repeated doses of indomethacin on fetal rabbit mortality and on the patency of the ductus arteriosus
Authors: Harris W. H.
Published: April 2011

The effects on fetal mortality and on the patency of the ductus arteriosus of several doses of indomethacin administered at different frequencies to pregnant rabbits were studied. The data show that the number of intrauterine deaths was related to both the dose and frequency of indomethacin administration. However, the degree of constriction of the ductus arteriosus of the dead fetuses was approximately the same, regardless of the dose or the frequency of drug administration. Therefore, the smaller doses may have caused constriction of the ductus for a sufficiently short period of time as not to be lethal in all cases whereas the constriction produced by the larger doses would be of greater duration and more likely to cause death. Although both maternal and fetal plasma concentrations of drug were elevated, there were litters in which no fetal deaths occurred. As the Cesarean sections were performed at various times after the last maternal injecion of drug, there was no evidence of a relationship between the dose of drug and the plasma concentrations. However, the fetal plasma concentrations of indomethacin were consistently higher than that of the doe, suggesting that the monitoring of only maternal plasma concentrations of some drugs may be a poor index of the amount of drug in the fetal circulation.
An unexpected increase in pituitary sensitivity to gonadotropin releasing hormone after treatment with porcine follicular fluid (inhibin) in immature hemicastrate rats
Authors: Wilkinson M. , Moger W. H. , Selin Liisa K.
Published: April 2011

Porcine follicular fluid (PFF) contains a factor (inhibin or folliculostatin) which is reported to selectively inhibit the secretion of follicle-stimulating hormone (FSH) from the anterior pituitary gland. Chronic treatment of hemicastrate immature rats with PFF is able to partially inhibit the FSH-mediated hypertrophy of the remaining testis. However, the pituitaries from PFF-treated rats are paradoxically very sensitive to stimulation with gonadotrophin-releasing hormone (GnRH) and secrete significantly more FSH than control glands. Furthermore, this increased sensitivity results in a large increase in luteinizing hormone (LH) secretion. These observations suggest that under certain circumstances PFF is not selective for FSH and that it surprisingly stimulates rather than inhibits gonadotrophin secretion.
Investigations into the mechanism of morphine and ethanol inhibition in the guinea pig ileum longitudinal muscle strip
Authors: Clement John G.
Published: April 2011

It has been noted that the analgesic property of ethanol bears a marked resemblance to that of morphine. The purpose of this study was to determine if the mechanism of action of morphine and ethanol was similar using the guinea pig ileal longitudinal muscle strip (GPI-LMS). Ethanol (35–260 mM) depressed the twitch response and the acetylcholine- (ACh-), KCl-, and BaCl2-induced contractions to the same extent while having no significant effect on the binding of [3H]quinuclidinyl benzilate ([3H]QNB) to muscarinic receptors. Morphine (53–530 nM) inhibited the twitch response and to a lesser extent BaCl2- and KCl-induced contractions while having no significant effect on either ACh-induced contractions or the binding of [3H]QNB to muscarinic receptors. Naloxone and increased [Ca2+] reversed the inhibitory effects of morphine but not ethanol. Ethanol appears to inhibit a site after interaction of ACh with the receptor. Mechanism of inhibition of BaCl2 response is also different as naloxone and increased [Ca2+] reverse morphine but not ethanol inhibition. Ethanol inhibition in GPI-LMS does not involve the opiate receptor.
Effects of isoproterenol on insulin and glucagon secretion in rats treated chronically with isoproterenol
Authors: Rousseau-Migneron Suzanne , Nadeau André , Tancrède Gilles
Published: April 2011

To better understand the mechanism(s) whereby chronic adrenaline treatment rendered rats less susceptible to the hyperglycemic effect of this catecholamine sharing both α- and β-adrenergic activities, a similar treatment was done with isoproterenol, a pure β-adrenergic agonist (300 μg/kg daily for 28 days). The dynamics of plasma glucose, insulin, and glucagon were studied in unanesthetized control and treated rats during an isoproterenol infusion (0.75 μg kg−1 min−1), an acute intravenous glucose load (0.5 g/kg), or the simultaneous administration of both agents. Chronic treatment with isoproterenol did not modify the basal glucose and glucagon levels but it greatly diminished the insulin values (40.1 ± 3 vs. 59.6 ± 3.6 μU/mL, p < 0.01). In both groups, the isoproterenol infusion produced an increase in glucose concentration which was associated with a prompt rise in insulin levels; however, the glucose and insulin elevations were significantly lower in the isoproterenol-treated rats than in the control animals (p < 0.01). Despite these glucose and insulin increases, plasma glucagon concentrations similarly rose during the first 15 min of infusion in both groups, followed by a return to their basal levels. During the intravenous glucose tolerance test, the plasma glucose, insulin, and glucagon responses showed similar patterns in both groups of rats; however, during the concomitant isoproterenol infusion, the treated rats showed a better glucose tolerance than their controls. Similarities with results obtained with adrenaline treatment suggest that adaptation to the hyperglycemic effect of both catecholamines may be mediated by desensitization at the β-receptor level; furthermore, such a modification may lead to an increase in the sensitivity to insulin.
Responses of rabbit renal artery to histamine: receptor type and temperature dependence
Authors: Cook D. A. , Iwanow D. M.
Published: April 2011

The effects of histamine on spiral strips of rabbit renal artery have been recorded. Histamine causes dose-dependent contractions of this preparation which are not antagonized by the H2 receptor blocking agent metiamide, but which are blocked by the H1 antagonist diphenhydramine. The p42 for the latter agent is similar to that observed at 37 °C in intestinal smooth muscle. No evidence of a relaxant population of H2 receptors was encountered.Unlike that of intestinal smooth muscle, the response of strips of renal artery becomes progressively diminished at temperatures below about 20 °C, and the effect of reduced temperature on receptor subtype is thus more difficult to assess. It appears, however, that there is no change in type from the H1 receptor observed at 37 °C and thus the temperature-dependent transformation which has been reported previously does not occur in all H1 systems.
Convulsive and hypothermic effects of vasopressin in the brain of the rat
Authors: Kasting N. W. , Veale W. L. , Cooper K. E.
Published: April 2011

Arginine vasopressin (AVP) was administered into the lateral cerebral ventricles of rats to assess its effects when given directly into the brain. AVP (1.0 μg) caused an immediate sharp decrease in body temperature. Behaviorally, AVP caused short pauses of immobility and staring upon the first injection but the same dose caused myoclonic–myotonic convulsions upon the second injection 2 days later. Thereafter, as little as 10 ng of AVP caused seizures.
The quasistatic elastic properties of longitudinal strips of the canine aorto–iliac bifurcation
Authors: Siu Peter I. S. , Roach Margot R.
Published: April 2011

The quasistatic elastic properties of the abdominal aorta, external iliac artery, and their junctional area in 10 mongrel dogs were measured.Arterial strips were excised with a double-bladed cutter. The strips contained roughly equal lengths of abdominal aorta and external iliac artery, with a width which included half the circumference of the aorta and the whole of the iliac artery. Each tissue strip was divided into three regions, i.e., abdominal aortic region, bifurcation region, and external iliac region. An India ink grid was painted on each region for measurement of the elongation in each region during stretching. Uniaxial tensile stress at a strain rate of 0.08 min−1 was applied to each strip until it raptured, using an Instron machine. Pictures were taken before and during stretching. Test results were presented in the form of specimen loading versus time on the chart recorder. From these data, values of stress and strain were then calculated and plotted.The external iliac region was most extensible, especially at low tensile stress, the bifurcation was next, and then the abdominal aortic region. The initial modulus of the bifurcation (6.42 × 105 dyn/cm2 per 100% elongation; 1 dyn = 10 μN) was found to be lowest of any of the three arterial regions. Statistical analysis indicated that there was a significant difference between the initial modulus of the external iliac artery (9.58 × 105 dyn/cm2 per 100% elongation) while the difference was insignificant between abdominal aorta (7.49 × 105 dyn/cm2 per 100% elongation) and external iliac artery, even though histological studies showed that the abdominal aorta has a higher number of elastic lamellae per millimetre of wall thickness. This led to the speculation that the state and arrangement of the elastic lamellae in the bifurcation region make that area less able to resist distension, or that the elastic fibres have a weaker anchorage to the collagen in that region. There was, however, a progressive and significant decrease in the final modulus from the abdominal aorta (10.55 × 107 dyn/cm2 per 100% elongation) through the bifurcation (6.48 × 107 dyn/cm2 per 100% elongation) to the external iliac artery (4.77 × 107 dyn/cm2 per 100% elongation). This leads to the conclusion that the collagenous fibres were "strung" most closely in the abdominal aorta, least in the external iliac artery, and between in the bifurcation region.The torsional shearing strains which developed in the arterial strips under longitudinal loading varied from 0 to 0.048, and were much smaller than the corresponding longitudinal strains of 0 to 1.0. Therefore, the shearing strains which developed under loading were neglected. End effects due to the clamps were also found to play an insignificant role.
Motor reflexes of stomach elicited by phenyldiguanide in the rat
Authors: Rao K. S.
Published: April 2011

Intragastric pressure (IGP) as an index of gastric motor activity was used to investigate gastric motor responses elicited by phenyldiguanide (PDG) in rats under pentobarbitone anaesthesia. Phenyldiguanide injected into the atrium produced an inhibitory gastric motor response whereas an aortic injection resulted in an increase in IGP. Intracarotid injections were without effect. Atropine reduced the response to atrial PDG but not to aortic PDG. Cervical vagotomy abolished the response to both atrial and aortic PDG. Guanethidine and spinal transection abolished the response to atrial PDG only. It is concluded that PDG acts by stimulation of nonmedullated vagal afferents. The efferent pathway for PDG-evoked gastric relaxation is through sympathetic nerves and the efferent system for gastric contraction involves a noncholinergic, nonadrenergic excitatory mechanism.
The sarcomere length – isometric tension diagram of the toad Bufo bufo sartorius
Authors: Bressler Bernard H.
Published: April 2011

The sarcomere length – isometric tension diagram has been determined for the toad Bufo bufo sartorius using a laser diffraction technique to measure the sarcomere width. The sarcomere width at l0 was found to be 2.37 μm. At lengths shorter than l0 this whole muscle exhibits a steeper decline in tension than single fibres. This discrepancy in the shape of the tension–length diagram between single frog fibres and whole toad sartorii may be due to a difference in the magnitude of the internal force which appears only at short lengths.
Activation of prorenin by proteases from polymorphonuclear leukocytes
Authors: Cybulsky A. V. E. , Cox D.W. , Osmond D. H.
Published: April 2011

Inactive renin (prorenin) can be activated by certain proteases in human blood, of which a possible source in vivo is polymorphonuclear leukocytes (PMNs). We extracted enzyme from PMNs using methods established for the recovery of neutral and acid protease fractions, and tested their effectiveness on plasma prorenin in vitro. Neutral protease preparations, possessing mainly chymotrypsin and elastase activity, produce no activation of prorenin. Exogenous pancreatic α-chymotrypsin does activate plasma prorenin, but less effectively than trypsin. From the quantity of PMNs extracted for neutral protease, and its failure to activate prorenin, we deduce that this enzyme preparation, like exogenous chymotrypsin, is qualitatively unimportant. In contrast, the extracted PMN acid protease fraction, believed to be rich in cathepsin D, exhibited high prorenin activating ability, suggesting both quantitative and qualitative importance. The low pH requirement of this acid protease (near pH 4.0), together with its inactivity at neutral pH, argues against an important systemic role in the conversion of prorenin. However, it may contribute to systemic activation in partnership with other enzymes, or else play a specialized local role in situations where PMN concentration and activity increase, and the pH is on the acid side.
Regional blood flows and cardiac output distribution in rats during acute anemia or polycythemia
Authors: Ackermann U. , Veress A. T.
Published: April 2011

Radioactively labelled microspheres (15 μm diameter) were used to measure cardiac output (CO) distribution and blood flows in spleen, kidneys, and skeletal muscle before and after normovolemic anemia or polycythemia in anesthetized rats. Hematocrits were changed from 45 to 33% or from 45 to 59% by an exchange transfusion of homologous plasma or packed cells. Anemia was accompanied by a 39% increase in CO while polycythemia showed a 25% decrease. Following hemodilution the spleen as well as skeletal muscle received greater than normal fractions of CO and in each the flow increase was greater than expected from the fall in viscosity. The renal fraction of CO was unchanged. Following hemoconcentration "greater-than-normal" fractions of CO were distributed towards spleen and kidney. In these tissues the changes in flow were significantly greater than the change in resistance due to viscosity. Skeletal muscle flow changes appeared to have been due mostly to increased viscosity. These observations imply that during acute, isovolemic changes in hematocrit, the flow changes of individual vascular beds cannot be explained by viscosity changes alone but the importance of nervous control or of local metabolic factors remains to be investigated.
Effect of fasting on Na-K-ATPase activity in rat small intestinal mucosa
Authors: Murray D. , Wild G. E.
Published: April 2011

The effect of fasting on mucosal Na-K-ATPase activity in various regions of rat small intestine was investigated. Fasting (17-48 h) was associated with a consistent decrease in specific and total activity of Na-K-ATPase in the jejunum, the levels tending to rise more distally. No effect on the specific activities of Mg-ATPase or alkaline phosphatase was found. Fasting was also associated with increased adrenocortical activity and with decreases in mucosal mass, protein content, and histological dimensions of the jejunum, no similar changes being found in the distal small intestine. Glucose ingestion prevented the decrease in jejunal enzyme activity associated with fasting and elevated levels in the mid and terminal small intestine of fed animals. These effects suggest that Na-K-ATPase activity in small intestinal mucosa may be, in part, inducible.
Adenosine receptor activation in human fibroblasts: nucleoside agonists and antagonists
Authors: Bruns Robert F.
Published: April 2011

Adenosine (ED50 15 μM) causes a 50-fold increase in intracellular cyclic AMP in the VA13 human fibroblast line. A total of 128 nucleosides was tested as agonists and antagonists. Eight classes of compounds were found: full agonists (14 compounds), weak agonists (20), high-efficacy partial agonists (16), low-efficacy partial agonists (7), competitive inhibitors (11), noncompetitive inhibitors (3), partial agonist - noncompetitive inhibitors (3), and inactive compounds (54). The noncompetitive inhibitors antagonized the responses to adenosine, isoproterenol, and prostaglandin E1 and thus may have been adenylate cyclase inhibitors. The most potent noncompetitive inhibitor, 2′,5′-dideoxyadenosine, was a partial inhibitor, reducing the response to isoproterenol by only 77% even at very high concentrations. The most potent agonists, partial agonists, and pure antagonists had apparent affinities of about 5 μM. Although all positions were important for affinity at the adenosine receptor, only the 3′- and 5′-positions and to a much lesser extent the 6- and 8-positions had an effect on efficacy. The receptor tolerated bulky groups at the 6-position of adenosine, had an ethyl-sized "pocket" near the 5′-position, and had little bulk tolerance towards modifications at other positions. Among the full agonists, only one 5′-derivative and one 2-position derivative had higher apparent affinity than adenosine. Studies with conformationally restricted agonists and antagonists showed that adenosine must be in the anti conformation in order to bind to the receptor.
The effects of four platelet inhibitors on human platelets using two adhesiveness test systems
Authors: McIntyre B. A. , Philp R. B.
Published: April 2011

The effects of the nonsteroidal anti-inflammatory drugs acetylsalicylic acid (ASA), naproxen (Naprosyn®, Syntex), and ibuprofen (Motrin®, Upjohn) and of the phosphodiesterase inhibitor VK 774 upon adhesion of human platelets to collagen fibers and to glass beads were compared after incubation with drug at two concentrations for 5 and 10 min. ASA significantly (p < 0.05−0.01) inhibited platelet adhesion to collagen fibers at the two concentrations (2.65 × 10−4 and 5.05 × 10−4 M) and after 5- and 10-min incubations. Naproxen inhibited adhesion significantly (p < 0.05−0.02) at the lower concentration (2.38 × 10−4 M) and at both incubation times. Ibuprofen did not significantly inhibit adhesion to collagen fibers. VK 774 significantly (p < 0.05−0.005) inhibited platelet adhesion to collagen fibers at both concentrations (2.38 × 10−4 and 4.54 × 10−4 M) and at both incubation times. ASA (1 × 10−3 M) produced slight but statistically significant (p < 0.05) inhibition of platelet adhesion to glass beads. Ibuprofen and naproxen (1 × 10−3 M) did not significantly inhibit adhesion in this test. VK 774 (1 × 10−3 M), however, significantly [Formula: see text] inhibited platelet adhesion to glass beads, to a greater extent than to collagen fibers. Naproxen (375 mg) was given orally in a single dose to five volunteer subjects. Bleeding time was doubled (p < 0.02) 2 h later and slightly but not significantly prolonged 24 h later. The second wave of platelet aggregation in response to ADP and adrenaline was completely blocked in all subjects 2 h after medication and still absent in one subject 24 h after medication, and higher concentrations of ADP and adrenaline were required to induce the second wave of aggregation in the remaining four subjects (4.2 × 10−6 M ADP and 5.6 × 10−5 M adrenaline in control period and 9.6 × 10−6 M ADP and 11.1 × 10−5 M adrenaline following drug administration). Collagen-induced aggregation was markedly inhibited 2 h after medication. These findings are in contrast with previously reported results with ibuprofen and suggest that naproxen induces greater impairment of hemostasis than does ibuprofen.
Substrate supply and function of isolated venous smooth muscle under anoxia and metabolic inhibition
Authors: Cremer-Lacuara M. G. , Lacuara J. L. , Cuneo M. Fiol de , Ruiz R. D.
Published: April 2011

The contractile recoverability of isolated portal veins made hypodynamic by removal of glucose from the perfusion medium by diverse exogenous substrates was studied. It was found that glucose, mannose, pyruvate, lactate, acetate, and butyrate readily restored contraction.The effects of anoxia and metabolic inhibitors were also investigated. Both anoxia and dinitrophenol abolished spontaneous activity within 10 min. Fluoroacetate markedly depressed contractility (−60.9 ± 2.8% at 10 min), the reduction being essentially similar in medium with or without glucose. 2-Deoxy-D-glucose (2-DG) in glucose medium reduced contractility only slightly whereas in the absence of glucose it drastically inhibited contraction (−76% at 10 min and −97% at 40 min).Intracellular ATP was significantly reduced by anoxia and fluoroacetate in medium with or without glucose and by 2-DG only in substrate-free medium. However, ATP depletion showed no clear correlation with the extent of contractile depression.These findings indicate a strong dependence for mechanical activity in this vein on aerobic metabolic pathways. But, from the results with 2-DG, it is suggested that an adequate glucose metabolism might be of importance for functional processes other than contraction itself.
Alterations induced by alloxan-diabetes and starvation on functional activity of the rat portal vein perfused in vitro
Authors: Cuneo M. Fiol de , Cremer-Lacuara M. G. , Ruiz R. D. , Lacuara J. L.
Published: April 2011

The levels of isometric developed tension (IDT) in portal veins from starved and diabetic rats in glucose medium were of the same magnitude but significantly reduced compared with veins from normal rats. Glucose removal led to contractile depression, more marked in starved veins (−74%; p < 0.001 vs. diabetics and normals). Addition of glucose, pyruvate, acetate, lactate, or butyrate counteracted this depression in all groups but in diabetics butyrate significantly stimulated IDT over controls whereas in starved veins lactate overcame IDT reduction only partially.Added insulin significantly enhanced contractile recovery with glucose in normal and diabetic preparations but was ineffective in starved veins.Glycogen content was significantly lower in diabetics; however, in no group did changes occur in incubated veins as compared with unincubated ones. Glycerol production was significantly higher in diabetic veins.It would appear that, although experimental diabetes induces a shift to fatty acid utilization, aerobic glycolysis and mitochondrial respiration are somehow preserved as reflected by the IDT recovery with pyruvate or lactate.
Liver lipid metabolism and effect of cholesterol-lowering agents in the hyperlipidemia induced in rats by implantation of the pituitary-derived MtT-F4 tumor
Authors: Huang Yung-Sheng , Asselin Michel , Gianoulakis Christina , Lis Martin , Chrétien Michel , Davignon Jean
Published: April 2011

Subcutaneous implantation of the transplantable pituitary tumor MtT-F4, which secretes large amounts of prolactin, growth hormone, and ACTH, produces hyperlipidemia in less than 30 days in the Fisher 344 rat. Further characterization of this new experimental model of endogenous hyperlipidemia showed that, at the 35th day after implantation, the hypertriglyceridemia may begin to subside while the elevation of plasma cholesterol progresses. At this time, acetate incorporation by liver slices into cholesterol is increased 27-fold while incorporation into fatty acids is 9 times as high as in sham-operated rats. Three drugs, probucol, hydroxymethylglutaric acid, and clofibrate, capable of lowering plasma cholesterol in these animals, also reduced the tumor-induced effect on cholesterol synthesis by about 60%. Only the latter two drugs, however, suppressed fatty acid synthesis to a similar extent. These experiments suggest that enhanced hepatic synthesis of cholesterol is in part responsible for the tumor-induced hypercholesterolemia.
Effects of isolated heat-stable enterotoxin produced by Escherichia coli on fluid secretion and cyclic nucleotide levels in the jejunum of the weanling pig
Authors: Scoot A. , Forsyth G. W. , Kapitany R. A. , Roe W. E. , Hamilton D. L.
Published: April 2011

Fluid secretory responses and associated changes in cyclic nucleotide concentration caused by the heat-stable enterotoxin of Escherichia coli (ST) have been investigated in the jejunum of weanling pigs. Effects associated with ST treatment have been compared with the actions of cholera toxin (CT) in the same experimental model. Positive correlations were obtained for the log of the ST dose correlating with net fluid secretion and with mucosal cyclic GMP (cGMP) concentration. Net fluid secretion rates could be predicted by mucosal cGMP concentration except for a brief interval when secretion was returning to control levels following ST removal from loops. Secretion rates in this post-ST period correlated more closely with the ratio of cGMP to cAMP concentration than with cGMP levels alone. Attempts to decrease the cGMP concentration and the secretory rate by combining CT and ST treatment were not successful. We conclude that the previously observed lack of cAMP response to CT in the pig may not be due to major differences in secretory control in that species. The pig is similar to other animal models where changes in mucosal cGMP concentration are associated with net jejunal fluid secretion induced by ST.
Effect of adenosine uptake inhibition on the nature and potency of theophylline as a presynaptic adenosine receptor antagonist
Authors: Clanachan A. S. , Muller M. J.
Published: April 2011

The nature and potency of theophylline as a presynaptic adenosine receptor antagonist was investigated in rat vas deferens in vitro.Schild plots were constructed and the pA2 and the slope were determined when the presynaptic adenosine receptor agonist was (a) adenosine alone, (b) adenosine following adenosine uptake inhibition by hydroxynitrobenzylthioguanosine, and (c) 2-chloroadenosine, a potent adenosine analogue which appears not to be a substrate for the adenosine uptake system. The pA2 values for theophylline were 3.80, 4.58, and 5.61, respectively, and the slopes of the Schild plots were 0.58, 0.71, and 0.78, respectively.The variation in the apparent potency of theophylline as a presynaptic adenosine receptor antagonist is explained according to Furchgott's prediction that removal of an agonist from the vicinity of its receptor upsets the equilibrium between agonist and receptor and so may influence antagonist – receptor interactions.Because adenosine uptake varies among tissues, this process should be eliminated before attempting to compare potencies of adenosine receptor antagonists or to classify adenosine receptors by pA2 values.
Pharmacological modulation of cholinergic neurotransmission in guinea pig trachea in vitro
Authors: Jones Thomas R. , Hamilton John T. , Lefcoe Neville M.
Published: April 2011

Electrical (field) stimulation of the isolated guinea pig trachea with normal intrinsic tone produced a biphasic response which consisted of an initial (cholinergic) contraction followed by (adrenergic and nonadrenergic) relaxation. Treatment of the tissue with the prostaglandin synthetase inhibitor indomethacin (2.8–5.6 μM) removed intrinsic tone and increased the responsiveness of the tissue to stimulation of cholinergic nerves and to exogenous acetylcholine. Indomethacin-relaxed tracheae were subsequently used to study cholinergic neurotransmission because under these experimental conditions only the contractile component of the response to electrical stimulation was observed. The β adrenoceptor blocking agents dl-propranolol and sotalol and the adrenergic neuron blocking agent guanethidine produced further enhancement of the contraction to electrical stimulation at low frequency (1–10 Hz). Prostaglandin E1, l-noradrenaline, l-adrenaline, salbutamol, phenylephrine, and phentolamine selectively attenuated the contractions to electrical stimulation in concentrations which did not significantly alter the matched responses to exogenous acetylcholine. The selective depressant effect of l-noradrenaline, l-adrenaline, salbutamol, phenylephrine, and phentolamine but not prostaglandin E1 were blocked by dl-propranolol or sotalol. The present results demonstrate that responses to stimulation of cholinergic nerves were altered by (1) prostaglandins and inhibitors of their synthesis, (2) neurally released adrenergic transmitter, and (3) exogenously added β adrenoceptor agonists. The possibility that prostaglandins and adrenergic neurotransmitter may modulate cholinergic neurotransmission at both pre- and post-junctional sites is hypothesized. It is proposed that more attention should be paid to the role of cholinergic transmission and its modulation in the studies of airway smooth muscle.