bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal Vasoconstriction following Diuretic-Induced Volume Depletion: Role of Angiotensin and Vasopressin
Authors: McNeill J. Robert
Published: April 2011

Intravenous administration of furosemide, ethacrynic acid, or chlorothiazide induced intestinal vasoconstriction in pentobarbital-anesthetized cats. The vasoconstrictor response following furosemide was prevented by nephrectomy or by replacement of urinary losses, indicating the response was dependent upon the volume-depletion produced by the drug. The intestinal vasoconstriction following furosemide was not reduced in animals subjected to acute intestinal denervation, adrenalectomy, and hypophysectomy. Similarly the response was not reduced in animals subjected to intestinal denervation and adrenalectomy, and administered SQ20881, an inhibitor of angiotensin-converting enzyme. However, administration of SQ20881 to hypophysectomized animals completely abolished the vasoconstriction even when the intestinal innervation and adrenal glands remained intact. The results suggest that the renin–angiotensin system and the vasopressin system play major roles in the mechanism of the intestinal vasoconstriction following diuretic-induced volume depletion and that the sympathoadrenal system plays little role in this response.
The Effect of Intravenous Infusions of Angiotensin and Noradrenaline on Systolic Blood Pressure and Critical Opening Pressure of Tail Vessels in Conscious Rats
Authors: Darke A. C.
Published: April 2011

A spectroscopic technique for the measurement of systolic blood pressure and critical opening pressure of tail vessels in conscious rats is described. The values for systolic blood pressure obtained by this indirect technique were compared with those obtained by direct recording from a cannulated carotid artery. The correlation between the two sets of measurements was highly significant and the regression coefficient was very close to unity. In a separate series of experiments the effects of intravenous infusions of angiotensin or noradrenaline on the critical opening pressure of tail vessels were investigated in conscious ganglion-blocked rats. Both drugs produced dose-dependent increases in critical opening pressure and systolic blood pressure. This contrasts with the situation in the human finger where angiotensin has been shown to produce a decrease in critical opening pressure, indicating relaxation of a least some of the vessels in the finger, while at the same time producing an overall increase in digital vascular resistance.
Drug-Induced Porphyrin Biosynthesis—XII. Levels of Cytochrome P-450 in Chick Embryo Liver following Administration of Allylisopropylacetamide and Propylisopropylacetamide
Authors: Krupa V. , Creighton J. C. , Freeman M. , Marks G. S.
Published: April 2011

Allylisopropylacetamide caused a decrease in the level of chick embryo liver cytochrome P-450 1 h after administration, followed by an elevation above control levels at a later time period. Propylisopropylacetamide on the other hand did not produce an early decrease in cytochrome P-450 but produced an elevation of cytochrome P-450 at a later time period. Since propylisopropylacetamide is an inducer of δ-aminolevulinic acid synthetase activity and porphyrin accumulation in chick embryo liver, it was concluded that a loss of cytochrome P-450 is not a prerequisite for ALA-synthetase induction as is thought to be the case in rats.
Mechanism of Inhibition of Smooth Muscle Tension in Guinea-Pig Taenia Coli by Ouabain
Authors: Bose D.
Published: April 2011

Ouabain produced an increase in tension in the guinea-pig taenia coli which was abolished in the presence of high extracellular potassium. On the other hand the delayed inhibitory response of ouabain could only be abolished by the removal of extracellular sodium. The mechanism of inhibition of contraction by ouabain appears to be due to elevation of intracellular sodium concentration.
Responses to and Termination of Action of Prostaglandins in Vascular Tissue of the Rabbit
Authors: Kalsner Stanley
Published: April 2011

The capacity of vascular tissue to terminate the action of prostaglandins E1, E2, and F2α was investigated after contractions in rabbit aortic strips. The oil-immersion technique was used to eliminate diffusion of agonist from the tissue in order to focus on intrinsic pathways of disposition. Aortic strips contracted in Krebs solution by moderate concentrations of PGE1 E2, and F2α maintained a steady level of response undiminished during a 60 min period of oil immersion. Relaxation occurred promptly after return to Krebs solution. In contrast, strips contracted by noradrenaline relaxed rapidly in oil, reflecting the presence of efficient intrinsic processes of inactivation for catecholamines. It is concluded that aortic tissue lacks any intrinsic mechanism capable of reducing the concentrations of PGE1, E2, and F2α involved in the response of the intact preparation. Based on the present findings it appears that the actions of these prostaglandins are terminated by diffusion out of the tissue and under in vivo conditions this is followed probably by metabolism at distant organs such as the lungs and liver.
Catecholamine Binding and the Turnover Number of Adenylate Cyclase
Authors: Bär H. P.
Published: April 2011

Critical review of recent [3H]catecholamine/adenylate cyclase binding data reveals that turnover numbers of adenylate cyclase, obtained by dividing the specific activity by binding activity, are unreasonably low (0.000074–1.67 s−1). Unless unusual assumptions are made, this supports the idea that the observed binding is unrelated to cyclase-associated β-adrenergic receptors.
Antagonism of Hydrochlorothiazide-Induced Elevations in Plasma-Renin Activity by Methyldopa in Conscious Renal-Hypertensive Dogs
Authors: Sweet Charles S. , Wenger Herbert C. , O'Malley Theresa A.
Published: April 2011

Hydrochlorothiazide, 2.5 and 10 mg/kg per day, was administered alone and in combination with methyldopa, 200 mg/kg per day, and changes in plasma-renin activity and mean arterial blood pressure were measured in conscious hypertensive dogs during a 7-day treatment period. Hydrochlorothiazide did not lower mean arterial blood pressure although there was a substantial increase in plasma-renin activity. When methyldopa was administered in combination with hydrochlorothiazide, a significant decline in both blood pressure and plasma-renin activity was observed. Since methyldopa was hypotensive only when coadministered with hydrochlorothiazide, the results suggest that antihypertensive effects of methyldopa in the diuretic-treated dog may depend in part on suppression of renin release.
Excitation–contraction coupling in heart. XIX. Effect of hypoxia on calcium transport by subcellular particles in the isolated perfused rat heart
Authors: Lee S. L. , Balasubramanian V. , Dhalla N. S.
Published: April 2011

To examine the role of changes in calcium transport by subcellular particles in the pathogenesis of contractile failure due to oxygen lack, both mitochondrial and microsomal fractions were obtained from the isolated hypoxic rat hearts and their calcium binding and uptake abilities were determined by the Millipore filtration technique. The contractile force decreased by about 40, 60 and 70% of the control within 5, 10 and 30 min respectively, of perfusing the heart with hypoxic medium containing glucose. In hearts perfused for 10 min with hypoxic medium containing glucose, calcium binding and uptake by the microsomal fraction decreased significantly. However, mitochondrial calcium binding, but not uptake, decreased significantly on perfusing the hearts with hypoxic medium containing glucose for 20 to 30 min when the microsomal calcium transport was markedly depressed. Reduction in contractile force, calcium binding and uptake by the microsomal fraction as well as calcium binding by mitochondria of hearts made hypoxic for 30 min recovered towards normal upon reperfusion with control medium for 15 min. On the other hand, omitting glucose from the hypoxic medium significantly decreased calcium binding by mitochondrial and microsomal fractions within 10 min of perfusion in comparison to the control and accelerated the effects of hypoxia upon contractile force and microsomal calcium uptake. In contrast to the hypoxic hearts, the mitochondrial calcium uptake decreased significantly and the magnitude of depression in the microsomal calcium binding was appreciably greater in hearts made to fail to a comparable degree upon perfusion with substrate-free medium. The observed defects in calcium transporting properties of microsomal and mitochondrial membranes appear secondary to the contractile failure in hypoxic hearts.
Effect of 6-hydroxydopamine on diet-induced hyperlipidemia and atherosclerosis in the rat
Authors: Lelorier J. , Tremblay M. , Champlain J. de , Gattereau A. , Davignon J.
Published: April 2011

The effect of 6-hydroxydopamine (6-OH-dopamine) and of a cholesterol rich diet on the plasma and aortic cholesterol of female rats were studied. Both the diet and the 6-OH-dopamine produced an important increase in plasmatic and aortic cholesterol. A synergistic effect of these two treatments was observed on the plasma but not on the aortic cholesterol. The mechanism by which 6-OH-dopamine produces hypercholesterolemia and an increase in aortic cholesterol remains to be explained.
Muscle fiber capacity in low conductivity solution
Authors: Loo D. , Vaughan P. C.
Published: April 2011

A method is described for computing the effective capacity of muscle fibers, C = Q/V where Q is the charge stored, and V is the membrane potential, using a standard two-microelectrode, constant current injection technique. The method is used to compare physical (or effective) capacity of frog muscle fibers bathed in a low conductivity, 2.5 mM K+ solution, with circuit-theory derived quantities in the same cells and in control fibers. No differences can be discerned and it is concluded that low conductivity of physiological solutions, per se, does not significantly reduce the length constant of frog muscle transverse tubules.
The perifused isolated left atrium: a preparation for studies on sugar transport in the myocardium
Authors: Sawh P. C. , Bihler I.
Published: April 2011

A procedure is described for the in vitro perifusion of the rat left atrium by recirculating medium through the atrial cavity and around the tissue, and for making the left atrium completely quiescent using surgical methods. The main advantage of this preparation is that it provides direct data on metabolic and transport processes in resting myocardium. Its use is illustrated by data on the time course, concentration dependence, insulin sensitivity and chemical specificity of the sugar transport system; in all these respects the resting left atrium resembles resting skeletal muscle.
Influence of the degree of hydrolysis of beef tallow on its absorption in the young pig
Authors: Swiss Lynn D. , Bayley H. S.
Published: April 2011

Beef tallow was hydrolyzed to produce a series of fats with 3, 10, 20, 46, and 100% free fatty acids, which were incorporated at the level of 10% into semipurified diets. These diets along with a low-fat control diet were each fed to five piglets from 10 to 22 days of age. Tridodecyl glycerol ether was used as an indicator of fat absorption. Feces samples were collected between 19 and 22 days of age and the pigs were killed to allow samples of digesta to be collected. Analysis of feces and digesta allowed the progress of fat absorption to be monitored through the digestive tract. The corrected absorbability of the total lipid was between 88 and 93% for the partially hydrolyzed tallows, but was only 75% for the completely hydrolyzed tallow. The oleic acid was well absorbed (95–99%) in all the diets; palmitic and stearic acids were also well absorbed in the intact and partially hydrolyzed tallow (82–84% and 63–77%, respectively, for the palmitic and stearic acids), but their absorption was impaired in the completely hydrolyzed tallow (62% and 38%, respectively, for the palmitic and stearic acids).The flow of fatty acid through the digestive tract showed that the small intestine is the major site of fat uptake. Comparison of the amounts of fatty acids in the ileal digesta and in the feces showed that there was no change in the total amount of fat in the digesta as it passed through the large intestine.
The composition of lipids in intestinal digesta of young pigs receiving diets containing tallow and tallow fatty acids
Authors: Swiss Lynn D. , Horney F. D. , Bayley H. S.
Published: April 2011

Three semipurified diets containing a low level of fat or 10% of either beef tallow or beef tallow free fatty acids were fed to young pigs. Jejunal digesta was sampled 1.5, 2.5, 3.5, and 4.5 h after feeding by aspiration through tubes leading from the jejunal lumen to the exterior. The samples were forced through Millipore filters (1 × 10−7 m pore size) to separate aqueous phase and oil phase lipid. The total and aqueous phase lipid was separated into triglyceride, monoglyceride, and free fatty acid, and the fatty acid composition of each fraction determined. The concentration of aqueous phase lipid was not influenced by diet, although the concentration of the oil phase lipid was generally higher for the addition of fat to the diets; the increase was greater for the beef tallow free fatty acid diet than for the beef tallow diet. Free fatty acids were the predominant component of the aqueous phase lipid along with some monoglyceride and traces of triglyceride. The major component of the oil phase lipid was free fatty acid but there were appreciable concentrations of triglyceride and monoglyceride. These must have been derived from endogenously secreted lipid in the case of the tallow fatty acid diet. Thus, the lower digestibility of completely hydrolyzed beef tallow than of conventional beef tallow was not due to an absence of monoglyceride in the intestinal lumen. The proportion of stearic acid in the jejunal digesta was greater than in the dietary lipid, whereas there were lower proportions of palmitic and oleic acids in the jejunal digesta than in the diet; the effect being most pronounced for the tallow free fatty acid diet. The ratio of oleic to palmitic acid in the aqueous phase was less than in the lipid phase suggesting preferential uptake of oleic acid from the micelle by the intestinal mucosa.
Uptake of ATP by liver and kidney in vitro
Authors: Chaudry Irshad H. , Sayeed Mohammed M. , Baue Arthur E.
Published: April 2011

Rat liver and kidney slices were incubated at 37 °C for 1 h in 1.0 ml of Krebs–HCO3 buffer containing 10 mM glucose and one of the following: 5 mM [8-14C]ATP, 5 mM [8-14C]ADP, 5 mM [8-14C]AMP, or 5 mM [8-14C]adenosine, together with 5 mM MgCl2 Samples of the incubation medium and tissue extract were subjected to electrophoretic separation and the radioactivity present in ATP, ADP, AMP, IMP, inosine, adenosine, and hypoxanthine was counted. Extensive degradation of the added nucleotide was observed in the presence of both tissues. The concentrations of 14C-labeled ATP and ADP found in the liver and kidney indicated that these compounds were present within the cells. Evidence is presented which suggests that ATP, and to a lesser extent ADP, entered the liver and kidney as such and were not synthesized within the cell from 14C-labeled adenosine.
Evidence for an ascending inhibitory histaminergic pathway to the cerebral cortex
Authors: Sastry B. S. R. , Phillis J. W.
Published: April 2011

Previous observations from our laboratory indicate that metiamide is a specific histamine antagonist in rat cerebral cortex. In view of the recent finding that histamine levels and L-histidine decarboxylase (EC 4.1.1.22) activity in cerebral cortex decrease following disruption of the ipsilateral medial forebrain bundle (MFB), the present investigation was undertaken to examine whether iontophoretically applied metiamide antagonizes the inhibition of deep cerebral cortical neurones produced by stimulation of the MFB. In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide and oxygen, stimulation of the ipsilateral MFB or the cortical surface with iontophoretically applied histamine depressed the firing of cortical neurones. Metiamide antagonized the histamine-induced depression and reduced the duration of inhibition produced by MFB stimulation. However, it did not alter the inhibition induced by the cortical surface stimulation. These results indicate that a histaminergic pathway ascending through the MFB may inhibit rat cerebral cortical neurones.
Survival of fasted rats exposed to altitude
Authors: Myles W. S.
Published: April 2011

Rats fasted for 48–96 h before exposure were shown to have a longer survival time at 33 500 ft (1 ft = 0.305 m) simulated altitude than nonfasted controls. Although both groups become hypothermic at 33 500 ft, colonic temperatures of the fasted rats were not sufficiently lower than those of nonfasted animals to explain the difference in survival time. The injection of glucose and insulin before exposure almost completely eliminated the protection afforded by fasting, whereas glucose alone had no effect on survival. It is therefore suggested that an alteration in carbohydrate metabolism, possibly in combination with other starvation-induced changes, allowed fasted rats to survive at 33 500 ft until declining body temperatures reduced metabolic rate to a level compatible with oxygen supply.
Long-term function of isotransplanted islets of Langerhans in the diabetic rat
Authors: Greenglass E. J. , Martin J. M.
Published: April 2011

Highly inbred male rats were made diabetic by subtotal pancreatectomy. After diabetes developed, the animals were transplanted with an average of 500 isolated islets, obtained from donors of the same sex and strain, into the portal vein. Groups of islet-transplanted diabetic rats were followed for periods of 3, 6, and 14 months, during which time the performance of the transplanted islets was investigated. Control animals were followed for similar periods of time. The findings obtained from each experimental group were integrated so as to provide a continuous picture of the transplanted islet's behaviour from 2 weeks to 14 months post transplantation.To assess islet performance, normal, untreated diabetic, and transplanted animals were subjected to three stimulatory tests of insulin secretion: (1) oral glucose tolerance, (2) intravenous sulfonylurea, and (3) intraperitoneal L-arginine. Normal and transplanted rats were additionally subjected to one inhibitory test of insulin secretion, diazoxide (given orally). At the end of the study, control and experimental animals were killed, and morphological investigations were performed on liver and pancreas.Isotransplantation of islets in partially depancreatized diabetic rats resulted in the reversal of the condition. The transplanted islets were found to respond to physiologic and pharmacologic controls, although the characteristics of the responses were not identical with that of the normal intact islet. The results of this study have suggested that a functional development of the transplanted islets occurs.
Evoked release from guinea pig cerebral cortex slices of endogenous 14C-labelled amino acids, labelled via D-[U-14C]glucose
Authors: Potashner S. J.
Published: April 2011

Release of endogenous amino acids labelled via D-[U-14C]glucose was compared with that of several exogenous labelled amino acids using slices of guinea pig cerebral cortex. Electrical field stimulation evoked a selective release of endogenous [14C]glutamate, [14C]aspartate, and γ-amino[14C]butyrate (14C-labelled GABA). The selectivity of release correlated well with 14C incorporation into endogenous amino acids. Calculations of the fraction of the tissue radio-activity released indicated that the selectivity was not an artifact due to differential incorporation. Because glucose in mammalian brain is metabolized almost entirely by the so-called 'large compartment', it is tentatively concluded that the releasable 'transmitter pool' of glutamate, aspartate, and GABA is located in this 'large compartment'.
Effects of chronic ethanol administration in the rat: relative dependency on dietary lipids. II. Paradoxical role of linoleate in the induction of hepatic drug-metabolizing enzymes in vitro
Authors: Joly Jean-Gil , Hétu Claude
Published: April 2011

The effect of chronic ethanol administration on the hepatic microsomal cytochrome P-450 content and activities of NADPH – cytochrome P-450 reductase (EC 1.6.2.4), benzphetamine demethylase, aniline hydroxylase (EC 1.14.14.1), and of the microsomal ethanol-oxidizing system were studied in various dietary models. When ethanol was given with linoleate as the only source of dietary lipid, the ethanol induction of these parameters was greater with diets containing 2 or 5% of total calories as linoleate than with diets containing 10% of total calories as linoleate. By contrast, when ethanol was given with high fat (35% of total calories) diets, the ethanol induction of these same parameters was slightly greater when linoleate provided 10% of total calories than when it provided 3% of calories. The apparent effect of dietary linoleate on the induction, by ethanol, of microsomal drug-metabolizing enzymes is markedly different when linoleate is given as the only source of dietary lipid as opposed to when it is given with other dietary lipids. Thus, conclusions on the effect of ethanol on hepatic microsomal drug-biotransformation enzymes, drawn from studies with dietary models in which linoleate provides the only source of dietary lipid, cannot be extended to dietary models of more complex lipid composition. When given as the only source of lipid, 2% of total calories in linoleate appears optimal for basal activity and inductibility, by ethanol, of mixed-function oxidases.
The effect of fasting on the in vitro synthesis of amylase in rat exocrine pancreas
Authors: Vieira-Matos Ana N. , Tenenhouse A.
Published: April 2011

Immunological methods were used to study the effect of fasting on the in vitro synthesis of amylase (EC 3.2.1.1) in rat exocrine pancreas. After 72 h of fasting, the amylase enzyme activity of the pancreas and the rate of amylase synthesis were reduced 50%. No significant change in the activities of trypsin or chymotrypsin were detected. The decrease in leucine incorporation in total pancreas protein was accounted for by the decreased amylase synthesis. No change in the rate of amylase breakdown was detected. These results indicate that the rate of synthesis of amylase is controlled by food intake and is not directly related to the tissue content of enzyme.
The effect of theophylline on amine-induced cardiac cyclic AMP and cardiac contractile force
Authors: Martinez Terry T. , McNeill John H.
Published: April 2011

In the isolated electrically driven rat atria, theophylline (5 × 10−4 M) produced a small but significant increase in cyclic AMP content which was prevented by reserpine pretreatment. Theophylline was also found to exert a direct contractile effect, unrelated to cyclic AMP, in atria obtained from reserpine-pretreated animals. The norepinephrine inotropic response was attenuated after 3 min, enhanced after 15 min, and abolished after 60 min of exposure to theophylline (5 × 10−4 M). The maximum phenylephrine inotropic response was not significantly changed after 15 min of exposure to theophylline; however, there was a slight shift to the left of the phenylephrine dose–response curve. The effect of theophylline on cyclic AMP appeared to be additive with the norepinephrine and phenylephrine responses. The effect of theophylline on amine-induced cardiac cyclic AMP and contractile force showed no correlation between the contractile and the cyclic AMP effects at the different times tested. It is concluded that the inotropic effects of theophylline in rat atria are not mediated through cyclic AMP; instead, the methylxanthines may exert their effects on the heart through changes in calcium metabolism.
Discrete-trial control of morphine self-injection behaviour in monkeys: effects of injection dose and trials per session
Authors: Stretch Roger , Gerber Gary J.
Published: April 2011

Responding for intravenous injections of morphine was studied using a discrete-trials procedure in squirrel monkeys. For one group, each session consisted of 10 trials at an inter-trial interval of 15 min; for the second group, each session consisted of 100 trials at an inter-trial interval of 1.5 min. When different injection doses of morphine (1–1000 μg/kg per injection), including saline as a control procedure, were substituted at random for blocks of five consecutive sessions, the frequency of morphine self-administration was found to be an inverted U-shaped function of the injection dose. This relationship was observed in each group of monkeys, despite a 10-fold difference in the total amount of the drug which was available for self-administration per session when a given injection dose was substituted for both groups. The results show that the injection dose of morphine acted as a primary determinant of response probability, even under circumstances in which trial spacing imposed a significant delay between consecutive opportunities for drug self-administration.
The influence of a visual cue on muscle stretch reflexes
Authors: O'Riain M. D. , Blair R. D. G. , Murphy J. T.
Published: April 2011

Evidence has recently been presented indicating that muscle stretch reflexes have a large supraspinal component. This finding introduces the possibility that stretch reflex parameters may be modifiable by stimuli involving other modalities besides stretch. In this investigation, the effects of a visual cue on the reflex portions of the EMG activity following a sudden muscle stretch were examined. The results, obtained from the flexor carpi radialis muscles of six normal awake subjects, failed to show any significant change in the EMG parameters as a result of visual cues occurring at the instant of onset of muscle stretch. This was interpreted as indicating that visual inputs do not reach the areas of brain involved in the supraspinal reflex in sufficient time to modify the reflex.
Effect of renal vein pressure on urinary sodium and bicarbonate ions
Authors: Jobin J. , Hemmings R. , Plante G. E.
Published: April 2011

The present study was undertaken to assess the effect of renal vein pressure on sodium and bicarbonate transport under two opposite conditions of bicarbonate filtered loads. Unilateral partial occlusion of the renal vein (RVO) was induced in 17 mongrel dogs: renal vein pressure rose from 9 to 20, 25, and 30 mmHg in a stepwise fashion. Seven of these animals (group I) were studied during bicarbonate loading [Formula: see text] and six others (group II) were studied during metabolic acidosis, induced with ammonium chloride [Formula: see text]. In the four remaining dogs (group III), administered bicarbonate in the manner described for group I, acetazolamide was given in a bolus and sustained infusion to inhibit the carbonic-anhydrase-mediated fraction of bicarbonate reabsorption while renal vein pressure was being kept at 30 mmHg. Plasma pCO2 was maintained at constant levels in all studies.In group I, urinary sodium (UNaV) decreased from 203 ± 32 to 110 ± 17 μEquiv./min, and bicarbonaturia [Formula: see text] from 131 ± 21 to 79 ± 18 μEquiv./min during RVO. In group II, UNaV) dropped from 132 ± 32 to 81 ± 20 μEquiv./min while [Formula: see text] remained at 2 μEquiv./min. Urinary ammonium and titratable acid decreased from 12.6 ± 1.7 to 8.7 ± 1.2 and from 8.0 ± 1.6 to 5.5 ± 1.1 μEquiv./min, respectively, during RVO. In group III, UNaV averaged 208 ± 42, 132 ± 29, and 203 ± 37 μEquiv./min during control, RVO, and RVO plus acetazolamide, respectively. During these same periods, [Formula: see text] was 144 ± 22, 72 ± 23, and 155 ± 30 μEquiv./min. All the above changes observed in the experimental kidney were significant (p < 0.05). In contrast, the same parameters measured in the opposite control kidney remained unaffected. Glomerular filtration and renal plasma flow remained stable in group I but decreased slightly in groups II and III. Filtration fraction was unaffected, however.The data indicate that RVO influences Na and HCO3 excretion through mechanisms not obviously related to peritubular physical forces. Since acetazolamide abolishes the effect of RVO, the mechanism(s) of antinatriuresis could be related to renal carbonic anhydrase activity.
Metabolism of angiotensin II and some analogs in intact strips and in muscle preparations of rabbit aortae
Authors: Magnan J. , Regoli D.
Published: April 2011

The purpose of this work was twofold: (a) to develop a muscle preparation of the rabbit aorta free of adventitia and endothelium, and (b) to measure the metabolism of angiotensin II (ATII) in this preparation. The muscle was prepared by 'shucking-off' the adventitia layer and by eliminating the endothelium. Concentration–response curves to ATII and noradrenaline (NA) measured in the muscle preparation provided pD2 values for ATII and NA not significantly different from those observed in the intact aortic strip. However, the maximal tension developed by the two agonists averaged 20–30% of the maximal tension of the intact strips. Apparent diffusion of ATII, in and out of the tissue, was faster in the muscle while NA diffusion was not significantly different. Metabolism of ATII was measured at the plateau of contraction and after complete relaxation in both the muscle and the intact strip. Ten percent of ATII was metabolized at the plateau of the contraction and 50% after complete relaxation. Heptapeptide 1–7 was the metabolite found in both preparations. 1-β-Asp ATII was also broken down to heptapeptide 1–7 while 1-β-Asp,8-Phe-OMe-ATII resisted the degradation and was found unchanged even after 90 min of incubation. It is suggested that the enzyme which inactivates ATII is located in the smooth muscle cells and that it is a carboxypeptidase.
Absorption and distribution of sodium [2-14C]barbital in tissues of normal and dystrophic mice
Authors: Stephens Heather R. , Nadeau Denis , Sandborn Edmund B.
Published: April 2011

The absorption and distribution of [2-14C]barbital after oral administration was studied in various tissues, including skeletal muscle, of normal and dystrophic mice. There appeared to be a more rapid gastric emptying in the mutant homozygote as reflected in lower levels of the drug recuperated from the gastrointestinal tract. This resulted in initially higher plasma and tissue concentrations of barbital in the dystrophic mice. Two hours after oral administration, this kinetic profile was reversed so that less barbital remained in the tissues of the dystrophic mouse. The tissue:plasma concentration ratios were consistently, but not significantly, higher in all tissues of the dystrophic animals. Analysis of the half-life of the drug in both groups suggests that there is an increase in the distribution volume of barbital in the dystrophic mice. The phenomenon of more rapid absorption of the barbiturate seems to be more consistent as the symptoms of the disease progress. The altered absorption and disposition of barbital in various tissues of the dystrophic mouse support the concept that a generalized multisystemic disorder may be crucial to the pathogenesis of murine muscular dystrophy, in contradistinction to a purely myogenic origin.
Increased pressor responses to pressor agents in spontaneously hypertensive rats
Authors: Kubo T.
Published: April 2011

Pressor reactivity to a variety of pressor agents after partial ganglionic blockade induced with hexamethonium was investigated in intact, in spinalized, and in chemically sympathectomized, spontaneously hypertensive rats (SHR). Responses of unanaesthetized 6-month-old SHR to noradrenaline, phenylephrine, and angiotensin after hexamethonium administration (32 mg/kg) markedly exceeded those of unanaesthetized, age-matched normotensive Wistar–Kyoto rats (WKR). Responses of anaesthetized SHR to noradrenaline after hexamethonium administration (16 mg/kg) were also increased at the hypertensive stages but not at the prehypertensive stages, when compared with those of anaesthetized normotensive Wistar rats of respective ages. In spinalized and chemically sympathectomized preparations after hexamethonium administration (16 mg/kg), noradrenaline produced equal increases in blood pressure in 6-month-old SHR and WKR. It is suggested that the functional sympathetic nervous system is important for the hyperreactivity of intact SHR.
Cardiac edema in dogs: Proximal tubular and renal function
Authors: Mandin H.
Published: April 2011

In recent dog studies, intrapericardial injection of Freund's adjuvant resulted in sodium retention, pulmonary edema, liver congestion, and ascites. Twenty-two experiments were initiated 6–13 days after pericardial injection. Micropuncture and clearance measurements were made during chronic cardiac tamponade (CCT) and 60 min after pericardiocentesis (PC). Following PC, sodium excretion (UNaV) increased from 12.2 to 41.3 μequiv./min. Glomerular filtration rate (GFR) during CCT was unaltered (from 37.3 to 38.7 mL/min) by PC. Single nephron glomerular filtration rate (sngfr) increased 23% (p < 0.005). Proximal fractional reabsorption (FR) decreased 6% after PC. Kidney filtration fraction (FF) increased from 0.35 to 0.38 (p < 0.01). Superficial nephron FF (six dogs) increased from 0.25 to 0.32 (p < 0.02). Peritubular capillary protein concentrations decreased following PC (from 7.41 to 6.89 g/100 mL), a result of decreasing systemic protein concentrations (from 5.51 to 4.69 g/100 mL). Tubule and capillary hydrostatic pressures (another six dogs) increased 6.2 and 3.3 mmHg, respectively, following PC (p < 0.05 and p < 0.005). The results indicate PC causes increased UNaV. GFR did not appear to influence UNaV. Decreased FR in the proximal tubule is secondary to increased sngfr, absolute absorption (C) remaining unaltered. The behaviour of C is in part explained by diminished capillary oncotic pressure and increased capillary hydraulic pressure.
Permeation of sodium through calcium channels of an insect muscle membrane
Authors: Yamamoto D. , Washio H.
Published: April 2011

The contribution of Na ions to the electrically excited response was studied in the muscle fibres of mealworm larvae, Tenebrio molitor, using microelectrode techniques. When Ca ions were omitted from the external solution, no action potential could be elicited. However, addition of Na ions to Ca-free medium rendered the fibre excitable again. The amplitude of these action potentials increased with a slope of about 40 mV for a 10-fold elevation of external Na concentrations. Tetrodotoxin had no effect on the initiation of the spike, and Co ions completely suppressed it. Therefore, it seems likely that a Ca-channel, which is utilized by both Na and Ca ions, is the sole factor responsible for the action potential in the mealworm larval muscle fibre membrane.
Serotonin receptors on astrocytes in primary cultures: Effects of methysergide and fluoxetine
Authors: Hertz L. , Baldwin F. , Schousboe A.
Published: April 2011

A specific binding of serotonin (at least 50 fmol/mg protein) was demonstrated in mouse astrocytes in primary cultures. This binding was inhibited by methysergide and by fluoxetine.
Effects of plasma cholesterol lowering agents on hepatobiliary lipid metabolism and cholesterol turnover in the rhesus monkey
Authors: Redinger R. N. , Passi R. B.
Published: April 2011

The effects of clofibrate, cholestyramine, and neomycin on hepatobiliary lipid metabolism were studied in adult rhesus monkeys in metabolic steady state with intact but exteriorized enterohepatic circulations. Clofibrate (30 mg/kg, id) had no effect on lipid secretion while cholestyramine (150 mg/kg, id) decreased biliary cholesterol secretion rate from 0.19 ± 0.03 to 0.13 ± 0.02 mmol/24 h, p < 0.05. Neomycin (30 mg/kg, id) decreased bile flow from 216 ± 10 to 191 ± 7 mL/24 h, p < 0.05, and tended only to decrease bile salt and phospholipid secretion rates. Cholestyramine decreased cholesterol composition from 1.81 ± 0.22 to 1.30 ± 0.22 mol%, p < 0.05, while clofibrate and neomycin had insignificant effects. Cholestyramine and neomycin decreased bile salt pool size from 1 ± 0.1 to 0.77 ± 0.15 and from 1.45 ± 0.16 to 1.13 ± 0.21 mmol, p < 0.05, respectively, while clofibrate had no effect. Bile salt synthetic rate was increased only by cholestyramine, i.e., from 0.63 ± 0.04 to 1.48 ± 0.26 mmol/24 h, p < 0.01. Concomitant cholesterol turnover studies revealed that cholestyramine increased the production rate and excretion of cholesterol in the rapidly miscible cholesterol pool and increased the transfer of cholesterol from slow to rapidly miscible pools. Neomycin, on the other hand, decreased the size of the rapidly miscible pool by decreasing production rate without affecting the size of the slowly miscible pool, while clofibrate had insignificant effects.
The mechanism of action of ionophore A 23187 on guinea pig intestinal smooth muscle
Authors: Rosenberger Lois B. , Triggle D. J.
Published: April 2011

The cation ionophore A 23187 behaves similarly to the potent muscarinic agonist, cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD) in guinea pig ileal longitudinal smooth muscle generating contractile responses that are gradedly sensitive to the concentrations of Ca2+ext and Na+ext. A 23187 and CD responses are insensitive to tetrodotoxin and A 23187 responses are insensitive to atropine. The responses to CD, A 23187, and veratridine are all similarly sensitive to the calcium antagonists D 600 and BAY-1040. D 600 failed to antagonize the ability of A 23187 to transport Ca2+ in a toluene-butanol: water two-phase system. It is suggested that in guinea pig ileal smooth muscle A 23187 does not translocate Ca2+ext exclusively but serves also to activate Ca2+ channels perhaps by an initial depolarizing Na+ entry.
Unit activity in the superior colliculus of the cat following passive eye movements
Authors: Abrahams V. C. , Anstee G.
Published: April 2011

Unit response in the superior colliculus and underlying structures has been examined in the chloralose-anaesthetized cat following passive movement of an occluded eye. One group of units was sensitive to small saccadic movements, responded regardless of the initial position of the eye, and in most instances responded to movements in opposite directions. A second numerically smaller group also responded when the eye was moved at saccadic velocity but only when the eye passed a fixed point. Such units with fixed positional thresholds were found following movements in both nasal and temporal directions as well as to both upward and downward movement. Both types of unit response were found after transection of the optic nerve and were also recorded when individual extraocular muscles were subjected to controlled stretch, It is assumed that most unit activity seen after passive movement of the occluded eye is due to activity in extraocular muscle receptors. In the deep layers of the superior colliculus responses to small eye movements were found to be due to the activation of very low threshold receptors sensitive to vibration in the facial area.
Receptors for bradykinin and kallidin
Authors: Drouin J. -N. , St-Pierre S. A. , Regoli D.
Published: April 2011

In order to establish if bradykinin (BK) and Lys-bradykinin (Lys-BK), alias kallidin, act on the same or on different receptors, experiments were performed on strips of cat terminal ileum and of rabbit aorta. The first preparation contains receptor B2 and the second has the newly identified receptor B1The criterion used for establishing the identity of receptors for BK and Lys-BK in the cat ileum (receptor B2) was desensitization, while for the rabbit aorta (receptor B1) we measured the apparent affinity (pA2 value) of a competitive and specific inhibitor of BK, [Leu-OMe8, des-Arg9]-BK. Since cat ileum desensitized with BK or Lys-BK shows a significant decrease or a complete disappearance of the response to the other agent, while maintaining full sensitivity for histamine, and since the pA2 values of [Leu-OMe8, des-Arg9]-BK against BK and Lys-BK are identical in the rabbit aorta, we conclude that the two kinins act on the same types of receptors.
The effects of muscarinic receptor blockers on the turnover rate of acetylcholine in various regions of the rat brain
Authors: Wood Paul L. , Cheney D. L.
Published: April 2011

The actions of antimuscarinic agents (benztropine, trihexyphenidyl, and scopolamine) on the dynamics of acetylcholine (ACh) in central cholinergic neurons were examined in various rat brain areas. It was found that the pattern of changes in ACh turnover (TRA Ch) elicited by these drugs exhibited marked regional variations. After administration of the anticholinergic drugs, the TRA Ch in hippocampus and thalamus was increased, in cortex it was decreased, and in striatum it was unchanged. ACh concentration in the cortex and striatum was decreased while in hippocampus and thalamus ACh levels were unaltered. Further analysis of the cholinergic septo–hippocampal pathway using lesions of the fimbria–fornix and local drug injections into the septum argue against an in vivo action of these drugs on presynaptic or ceil body muscarinic autoreceptors. Moreover, the data suggest that muscarinic receptor blockers cause an increased TRA Ch only in those areas where a feedback loop is operative, possibly by inhibiting a neuronal feedback loop involving at least one noncholinergic interneuron.
Pharmacological evidence for catecholamine-independent contractile effects of X-537A on the isolated working rat heart preparation
Authors: Rodgers Robert L. , Moore Joanne I. , Hornbrook K. Roger
Published: April 2011

The ionophore X-537A increased heart rate and contractility of the isolated, working rat heart preparation. The increased heart rate appeared to be caused solely by release of catecholamines as the response was completely eliminated by reserpine pretreatment or addition of propranolol to the perfusate. The inotropic response, however, had an apparent catecholamine-independent component as neither propranolol, nor propranolol in combination with phentolamine, completely eliminated the inotropic response to X-537A. On the other hand, reserpine pretreatment did abolish the inotropic effect of the ionophore but this action appeared to be a nonspecific one as the responses to norepinephrine and to CaCl2 were substantially diminished.
Diazepam potentiation of purinergie depression of central neurons
Authors: Phillis J. W.
Published: April 2011

Intravenously or iontophoretically applied diazepam potentiated the depressant action of iontophoretically applied 5′-AMP on the spontaneous firing of rat cerebral cortical neurons. This potentiation of purinergic depression may be a result of the previously reported inhibition by diazepam of uptake of adenosine into brain tissues.
Interaction of antidepressants with clonidine on rat brain total 3-methoxy-4-hydroxyphenylglycol
Authors: Tang S. W. , Helmeste D. M. , Stancer H. C.
Published: April 2011

The effects of some antidepressants on brain total 3-methoxy-4-hydroxyphenylglycol (MHPG) were studied in the rat. Desipramine decreased and mianserine increased the brain total MHPG concentration while the other antidepressants had no effect. They were also the only antidepressants that attenuated the lowering action of clonidine on brain total MHPG, but possibly through different mechanisms. Two tertiary amine tricyclic antidepressants, amitriptyline and imipramine, appeared to enhance the lowering action of clonidine on brain total MHPG. The results suggest that antidepressants are heterogeneous in their actions on brain noradrenergic mechanisms in the rat.
Effects of lanthanum on the heart sarcolemmal ATPase and calcium binding activities
Authors: Takeo Satoshi , Duke Peter , Taam Gina M. L. , Singal Pawan K. , Dhalla Naranjan S.
Published: April 2011

Effects of lanthanum on Ca2+-ATPase, Mg2+-ATPase, Na+–K+-ATPase, and calcium binding activities were studied in rat heart sarcolemma. Ten to 100 μM lanthanum depressed significantly the Ca2+-ATPase activity and 50–200 μM lanthanum inhibited the calcium binding activity. Lineweaver–Burk plots of the Ca2+-ATPase activity showed that the inhibition by lanthanum was competitive with calcium concentration. Neither Mg2+-ATPase nor Na+–K+-ATPase activities were affected by lanthanum when the assay medium contained 1 mM EDTA; however, in the absence of EDTA, these enzyme activities were significantly decreased by 10–100 μM lanthanum. Rat hearts perfused with HEPES buffer containing 0.5 mM lanthanum showed electron-dense deposits restricted to the outer cell surface and the sarcolemma obtained from these hearts also had the deposits, indicating that the membrane fraction isolated by the hypotonic shock – LiBr treatment method is of sarcolemmal origin. The Ca2+-ATPase activity of the sarcolemma isolated from lanthanum-perfused hearts, unlike the Mg2+-ATPase, Na+–K+-ATPase, and calcium binding activities, was significantly less than the control value. From these observations it is suggested that lanthanum may influence calcium movement across the sarcolemma by affecting sarcolemmal ATPase and calcium binding activities.
Inhibition of the cardiac inotropic effect of phenylephrine by a tetramine disulfide with irreversible α-adrenoceptor blocking activity
Authors: Benfey B. G. , Yong M. S. , Belleau B. , Melchiorre C.
Published: April 2011

The newly synthesized α-adrenoceptor blocking drug BHC (N,N′-bis[6-(o-methoxybenzyl-amino)-n-hexyl]cystamine) was found to block irreversibly the positive inotropic effect of the sympathomimetic drug phenylephrine on the isolated rat left atrium.BHC was used to test the adrenoceptor interconversion hypothesis which claims that low temperature converts inotropic β-adrenoceptors in rat atrium and frog ventricle to α-adrenoceptors.There was no evidence of adrenoceptor 'interconversion.' In the rat atrium low temperature did not increase the BHC antagonism of phenylephrine and did not cause BHC to inhibit the inotropic effect of noradrenaline or isoprenaline. In the perfused frog heart low temperature did not lead BHC to inhibit the inotropic effect of phenylephrine, adrenaline, or isoprenaline.
Vagal inhibitory effects on peripheral circulation in acute coronary occlusion
Authors: Pelletier Conrad
Published: April 2011

The reflex adjustments of the peripheral circulation in response to acute coronary occlusion were studied in anesthetized dogs with isolated vascular beds perfused at constant flow. Coronary occlusion caused significant increases in perfusion pressure which averaged 27 ± 4 mmHg in the hindlimb, 19 ± 8 mmHg in skeletal muscle, and 13 ± 5 mmHg in the mesenteric artery. These responses were less than half those caused by a similar decrease in aortic pressure obtained with hemorrhage. Coronary occlusion caused no significant changes in renal and paw-circulations, while marked vasoconstriction resulted from hemorrhage. When aortic pressure was maintained constant throughout the duration of coronary occlusion, there was a significant vasodilatation in all beds studied. After vagotomy, coronary occlusion caused a constrictor response similar in magnitude to that caused by hemorrhage in each vascular bed and the dilator responses to occlusion at constant aortic pressure were abolished. Both constrictor and dilator changes were prevented by alpha-adrenergic blockade. Mechanical distension of the left ventricle in four dogs with carotid sinus nerves cut caused a significant reflex dilatation in the hindlimb. Thus, coronary occlusion initiates an inhibitory reflex mediated by vagal afferents which opposes peripheral vasoconstriction most effectively in the renal and paw circulations.