bluuebunny/crossref_metadata_2025 huggingface dataset:
Different influences of two types of diets commonly used for rats on a series of parameters related to the metabolism of central serotonin and noradrenaline
Authors: Héroux Olivier , Roberge Andrée G.
Published: April 2011

A commercial chow and a semipurified diet fed for 14 days to Sprague–Dawley male rats kept under standardized conditions of temperature, humidity, and light had different effects on a series of parameters related to the metabolism of central serotonin and noradrenaline. Rats fed the commercial chow had (1) a lower serum level of the six neutral amino acids (valine, isoleucine, leucine, tyrosine, phenylalanine, and methionine) known to compete with tryptophan for its entry into the brain, (2) a higher ratio of tryptophan to the sum of the six neutral amino acids, (3) a lower ratio of tyrosine to the other five neutral amino acids, (4) a lower ratio of serotonin to 5-hydroxyindoleacetic acid in hypothalamus, (5) a higher tryptophan hydroxylase activity in raphe nuclei, and (6) a higher content of noradrenaline in hypothalamus.It is suggested that chow fed rats had a more active central serotonin metabolism in hypothalamus than rats fed the semipurified diet.
Contractile effects of 5-hydroxytryptamine in isolated intrapulmonary arteries and veins
Authors: Gruetter Carl A. , Ignarro Louis J. , Hyman Albert L. , Kadowitz Philip J.
Published: April 2011

The contractile effects of serotonin (5-hydroxytryptamine, 5-HT) were compared in helical strips of intrapulmonary artery (IPA) and vein (IPV) isolated from lungs of dog, rabbit, cow, and man. 5-HT (10−8–10−4 M) increased force generation by IPA and IPV from the four species in a concentration-related manner. Sensitivities to 5-HT of IPA and IPV from the four species were similar, with median effective concentrations ranging from 3 × 10−8 to 3 × 10−7 M. However, maximal contractile responses to 5-HT relative to those elicited by potassium were greater in canine and human IPA and bovine IPA and IPV than in rabbit IPA and IPV and canine and human IPV. Results obtained using specific pharmacologic blocking agents suggest that 5-HT-induced contraction of canine and rabbit intrapulmonary vessels does not involve α-adrenergic mechanisms except, possibly, in rabbit IPV. The contractile effects of 5-HT observed in the present study suggest that 5-HT released from platelets could contribute to increased vascular resistance during pulmonary thromboembolism by actively constricting arterial and venous segments of the pulmonary vascular bed in a variety of species, including man.
Maintenance of blood pressure by β adrenoceptor mediated renin release during different forms of anesthesia in rats
Authors: Leenen F. H. H. , Provoost A. P.
Published: April 2011

In rats we assessed the role of the sympathetic nervous system in the increase of plasma renin activity (PRA) following induction of anesthesia by urethane, ether, or pentobarbital and the role of these increased levels of PRA in the maintenance of blood pressure.Urethane and ether induced marked, sustained increases in PRA. Pentobarbital was less effective in this regard. Propranolol inhibited the response of PRA to urethane and ether in a dose-dependent manner but not the renin response to pentobarbital. Similarly, neonatal sympathectomy with 6-hydroxydopamine together with removal of the adrenal medulla prevented the renin response to urethane but not to pentobarbital.Blood pressure changed only slightly during urethane anesthesia, showed a sustained decrease during ether anesthesia, and a gradual return to normal following a marked initial drop during pentobarbital anesthesia. Saralasin pretreatment induced a marked decrease (40–45 mmHg; 1 mmHg = 133.322 Pa) in blood pressure during urethane anesthesia and smaller (10–20 mmHg) additional decreases during ether and pentobarbital anesthesia. In contrast, propranolol pretreatment did not significantly affect blood pressure during ether anesthesia and affected it to a minor degree (by 10–15 mmHg) during urethane and pentobarbital anesthesia.The results indicate that the increases in PRA following induction of anesthesia by urethane or ether, but not by pentobarbital, are mediated through the peripheral sympathetic nervous system via β adrenoceptors. The rennin–angiotensin system appears to be essential for the maintenance of a normal blood pressure during urethane anesthesia but plays a less prominent role in this regard during ether and pentobarbital anesthesia. The propranolol studies suggest that the hypotensive effect of propranolol through blockade of the renin response during urethane- and ether-induced anesthesia is masked by a pressor effect of propranolol.
Effect of ethanol on hepatic blood flow in unanesthetized dogs with chronic portal and hepatic vein catheterization
Authors: Villeneuve J. P. , Pomier G. , Huet P. M.
Published: April 2011

A method of chronic portal and hepatic vein catheterization in the dog is described. Using this method, hepatic blood flow was measured by an indicator dilution technique and the effect of acute ethanol administration on hepatic blood flow was evaluated in unanesthetized dogs. Intravenous and intragastric ethanol administration (2.0 g∙kg−1) resulted in a significant increase in hepatic blood flow. Splanchnic oxygen consumption was also increased following ethanol administration but this effect was offset by the rise in hepatic blood flow and the net result was an increase in hepatic vein oxygen content. These data demonstrate a significant effect of ethanol on hepatic blood flow but suggest that hepatic hypoxia does not occur following acute ethanol adminstration.
Proprioceptive input from the jaw muscles and its influence on lapping, chewing, and posture
Authors: Taylor A. , Appenteng K. , Morimoto T.
Published: April 2011

Experiments are described which define criteria for identifying fusimotor axons discharging in filaments of the masseter nerve in lightly anaesthetized cats. During reflex movements of the jaw two patterns of discharge were observed in different fusimotor fibres. One type, called "sustained," fired at a fairly constant increased rate. The other, called "modulated," fired at high frequencies during the extrafusal muscle contraction. Evidence from spindle primary and secondary recordings in similar experiments strongly suggests that the "sustained" type were dynamic fusimotor fibres and the "modulated" type were static fusimotor fibres. New spindle recordings in normal unanaesthetized cats indicate that the modulated pattern of static fusimotor discharge also occurs in these conditions. Its effect is to reduce the tendency for spindle afferents to become silent during muscle shortening. A proposal is made that the static fusimotor discharge in cyclic movements may represent a temporal "template" for the intended movement as directed by the central pattern generator.
Peripheral feedback mechanisms acting on the central pattern generators for locomotion in fish and cat
Authors: Andersson O. , Forssberg H. , Grillner S. , Wallén P.
Published: April 2011

The feedback mechanisms taking part in the control of locomotion in cat and fish are reviewed, particularly with regard to position- and movement-related feedback. It is shown that in both fish and cat there is a powerful position-dependent negative feedback which will act only in the position range where the muscle activity normally changes, e.g., from extensor to flexor activity. In addition, there is positive feedback in the middle of the movement range which will act in certain conditions, e.g., to promote and maintain flexor activity during the flexion of the hind limb.
Septo-hippocampal pathway modulates hippocampal activity by a cholinergic mechanism
Authors: Krnjević K. , Ropert N.
Published: April 2011

In rats under urethane, multibarrelled microelectrodes were used to record field responses of CA1 hippocampal pyramids evoked by fimbrial – commissural stimulation. A strong potentiation of population spikes could be obtained by either a local release of ACh or by a brief tetanic stimulation of the medial septum (which by itself evoked only minimal field responses of the hippocampus). Both effects were sharply reduced after intravenous injections of large doses of atropine or scopolamine, indicating that the septo-hippocampal innervation is to an important degree cholinergic and muscarinic. However, since dimethylphenylpiperazinium (a nicotinic ganglionic agonist) can also evoke population spikes, a significant though variable component of this cholinergic action may operate via nicotinic receptors.
Inhibition of the n-formylmethionyl-leucyl-phenylalanine induced respiratory burst in human neutrophils by adrenergic agonists and prostaglandins of the E series
Authors: Wong Kenneth , Freund Karen
Published: April 2011

Exogenous prostaglandins E1 and E2 and L-isoproterenol potently inhibited the production of superoxide anions by human neutrophils activated in vitro by n-formylmethionyl-leucyl-phenylalanine (FMLP). An estimated ID50 of 50 nM was found for all three agents while L-epinephrine and prostaglandin F2α were 10 and 100 fold, respectively, less active. Inhibition occurred whether these agents were added before, together with, or after the addition of the tripeptide to cell suspensions. Cells treated with dibutyryl adenosine 3′,5′-monophosphate also expressed reduced rates of superoxide synthesis thus suggesting that the hormonal inhibitors acted indirectly by stimulating membrane bound adenylate cyclase.
A theoretical discussion of the use of the Lineweaver–Burk plot to estimate kinetic parameters of intestinal transport in the presence of unstirred water layers
Authors: Thomson A. B. R.
Published: April 2011

Transport of a solute molecule from the bulk phase in the intestinal lumen into the mucosal cells is determined by the rate of movement of the solute molecule across two barriers, the unstirred water layers (UWL) and the microvillus membrane. Failure to account for the effect of the resistance offered by the UWL introduces significant errors into the estimate of kinetic constants of carrier-mediated transport, and these errors may be further magnified by the use of the Lineweaver–Burk plot. This study was undertaken to determine use of this plot under conditions that depict the effect of varying the effective resistance of the UWL, the distribution of transport sites along the villus (fn), the passive permeability coefficient (P), the maximal transport rate [Formula: see text], and the Michaelis constant (Km). Theoretical curves derived from a new equation demonstrate that (1) the Linewaver–Burk plot is linear under only a limited number of conditions, and even then may lead to serious over- or under-estimation of [Formula: see text] and Km; (2) failure to correct for passive permeation may give rise to additional quantitative discrepancies between the true and apparent values of [Formula: see text] and Km; and (3) the qualitative characteristics of a carrier-mediated intestinal transport system may be ascertained only after correction for the contribution of passive permeation, and after correction for the effective resistance of the UWL.
Effects of adrenaline and noradrenaline on the heat production of warm- and cold-acclimated sheep
Authors: Graham A. D. , Christopherson R. J.
Published: April 2011

The heat production (HP), heart rate (HR), respiration rate, rumen motility, and body temperature responses to 2.5-h adrenaline (A) and noradrenaline (NA) intrajugular infusions at 0.00, 0.15, 0.30, 0.60, and 0.90 μg∙kg−1∙min−1 were studied in 10 shorn wethers which had been chronically (3–8 weeks) exposed to warm (19–24 °C) or moderately cold (8–13 °C) temperatures. Heat production, as estimated from respired gas analysis, increased 40–45% with all doses of A and the effect was potentiated by chronic cold exposure. Only the higher dose rates of NA induced an increase in HP. The maximum HP increase due to NA was 30% and the effect was not influenced by chronic cold exposure. Thermoneutral HP was greater by 16–19% in cold-acclimated as compared with warm-acclimated sheep. Corresponding to the HP effects of A and NA, all doses of A and the highest dose of NA resulted in slight increases in rectal temperature. Respiration rate increased with increased dose rate of NA but only the highest dose of A resulted in an increase in respiration rate. HR, rectal temperature, and respiration rate responses to A and NA were not influenced by cold acclimation.
Effect of prostaglandins on rat heart sarcolemmal ATPases
Authors: Karmazyn M. , Tuana B. S. , Dhalla N. S.
Published: April 2011

The ability of prostaglandins (PG) D2, E1, E2, F2α and I2 (2.8 × 10−11 M to 2.8 × 10−7 M) to modify Ca2+, Mg2+ and (Na+ + K+)-ATPase activities of rat heart sarcolemmal membrane fractions was examined. Administration of PGE2, PGF2α, and PGI2 reduced basal (Na+ + K+)-ATPase activity by up to 30, 80, and 80%, respectively. PGE1 and PGD2 were ineffective at any concentration. Neither Mg2+-ATPase nor Ca2+-ATPase was affected by PG treatment. Kinetic analysis revealed that the (Na+ + K+)-ATPase activity reducing ability of PGE2, PGF2α and PGI2 was of a complex nature involving a reduction in Vmax and an elevation of the respective K values for either substrate or activator. These results demonstrate that some PG's are potent inhibitors of rat heart (Na+ + K+)-ATPase. These PG's produced varied inotropic influences on isolated heart preparations and it is uncertain whether their myocardial actions are dependent on enzyme inhibition.
Effects of porphyrin-inducing drugs on ferrochelatase activity in isolated mouse hepatocytes
Authors: Cole Susan P. C. , Massey Thomas E. , Marks Gerald S. , Racz William J.
Published: April 2011

The effects of several concentrations of griseofulvin and 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) on ferrochelatase activity in suspensions of isolated mouse hepatocytes were examined. In agreement with previous findings in the intact chick embryo liver and chick embryo liver cell culture, DDC, but not griseofulvin, inhibited the enzyme in the isolated mouse hepatocyte suspension. These results indicate that the difference between the effects of griseofulvin on hepatic ferrochelatase in rodents in vivo (inhibition), the intact chick embryo (no effect), and the chick embryo liver cell culture (no effect) cannot be attributed solely to species differences.
Lithium accelerates the development of tolerance to alcohol in rats
Authors: Boland Fred J. , Morgan C. Allison , Berry Paul C.
Published: April 2011

Thirty male Wistar rats, trained on the moving belt test, were used to test the effect of acute and chronic lithium administration on tolerance to alcohol. Over the first 11 days, a group receiving lithium (1.5 mequiv./kg, i.p.) 4 h before and alcohol (2 g/kg, i.p.) 17 min before three daily 2-min test trials on the moving belt showed accelerated development of tolerance to alcohol compared with a group receiving saline (instead of lithium) and the same dose of alcohol. There were no differences between the groups in the level of tolerance finally reached and no differences could be detected in the effects of lithium on physiological as opposed to behaviorally augmented tolerance. Also, 12 days of lithium pretreatment did not increase tolerance to an initial dose of alcohol or modify the expected blood alcohol level. Conversely, tolerance, as a result of 12 days of chronic alcohol pretreatment, was not increased further by a single lithium administration. Drug-free performance at the end of the experiment showed that the injection procedure per se did not influence performance.
Toxin-induced activation of muscle hydrolases
Authors: Boegman Roland J. , Scarth Brenda
Published: April 2011

Application of batrachotoxin, lysolecithin, tetrodotoxin, or veratridine to mouse skeletal muscle results in an increase in the activity of the following lysosomal enzymes: acid protease, acid phosphatase, and N-acetylglucosarninidase. Batrachotoxin caused the greatest increase in lysosomal enzymes while veratridine resulted in the smallest response. The increase in lysosomal enzymes was most marked within 1–2 days after toxin application and returned to normal values after 8–12 days.
A model for intracellular energy transport
Authors: Mainwood G. W. , Rakusan K.
Published: April 2011

A model for oxygen transfer to cells from capillaries is considered in which mitochondria are either clustered at the cell periphery around capillaries or homogeneously distributed through the cytosol. The capillary [Formula: see text] required to supply cells utilizing oxygen at the same rate is much less when mitochondria cluster around capillaries. Two alternative mechanisms are considered for distributing energy from peripheral mitochondria to the rest of the cell; i.e., diffusion of ATP or creatine phosphate with enough creatine kinase to ensure equilibrium between the ~P carriers. The latter has clear advantages and would appear to be adequate to supply a fairly large mitochondria-free cell core (e.g., 24-μm diameter) with very little change in ADP levels or in the free energy of ATP hydrolysis at maximum work rates. Thus, a viable alternative to the traditional Krogh model is presented which takes into account the inhomogeneity of the diffusion pathway as a result of mitochondrial clustering.
Unilaterality of the sympathetic innervation of each pad of rat interscapular brown adipose tissue
Authors: Foster David O. , Depocas Florent , Behrens Gloria Zaror
Published: April 2011

The effects of sham, unilateral, and bilateral surgical denervation of rat interscapular brown adipose tissue (IBAT) on blood flow to the two IBAT pads of cold-acclimated (CA) rats during exposure of the animals to 22 or −6 °C and on the noradrenaline (NA) content and total dopamine-β-hydroxylase (DBH) (EC 1.14.17.1) activity of the pads in both warm-acclimated (WA) rats and CA rats were examined. Increase in IBAT blood flow upon cold exposure was taken as an index of sympathetically mediated calorigenesis in the tissue, and decreases in tissue levels of NA and DBH served as indices of the extent of destruction of the sympathetic innervation. At 24 h postsurgery, denervated pads of CA rats, whether from unilaterally or bilaterally denervated IBAT, had less than 3% of the NA, 40-44% of the DBH, and 0% of the 10-fold, cold-induced increase in blood flow measured in intact pads of CA rats with sham-operated or unilaterally denervated IBAT. IBAT bilaterally denervated for 24 h was as responsive in terms of its maximum increase in blood flow during infusion of CA rats with NA as intact IBAT. DBH in denervated pads of both WA rats and CA rats fell to 5% or less of control levels at 2 days postdenervation and remained at these low levels, as did NA, for at least 8 weeks. These results strongly support the longstanding but recently challenged hypothesis that each pad of rat IBAT is independently innervated by sympathetic fibers.
Contractile characteristics of creatine-depleted rat diaphragm
Authors: Mainwood G. W. , Alward M. , Eiselt B.
Published: April 2011

Rats were fed on a diet containing the creatine analogue β-guanidinopropionate (Gp) in order to deplete muscles of creatine. Diaphragm muscle from these rats contains about 80% less creatine and creatine phosphate (CrP) than normal; ATP levels are reduced about 45%. When stimulated with single shocks or brief tetani, the contractile response of diaphragm strips is very similar to normal with some slowing of relaxation. During a burst of intense activity (0.2-s tetanic stimulation every 0.5 s) the maximum tension, rate of tension development, and rate of relaxation all decrease rapidly to reach a minimum about 3 s from the onset of activity. In contrast, normal muscles show a small decrease in tension and relaxation rate but an increase in the rate of tension development under these conditions. No large decrease in ATP levels could be detected when the contractile parameters reached a minimum. Three possible mechanisms considered for the decline in contractile parameters are the following: (1) local regions of ATP depletion around the myofibrils; (2) a fall in the free energy of ATP hydrolysis (dG/dξ) due to inadequate buffering by CrP; and (3) decreased rate of proton utilization in the region of the myofibrils, where ATP turnover is most rapid. All three mechanisms may contribute to the observed effects, although the second seems the most likely to play a dominant role in modifying the contractile response.
Renal intracortical blood flow and renin secretion after denervation by 6-hydroxydopamine
Authors: Bichet Daniel , Marc-Aurèle Julien
Published: April 2011

A new method of unilateral renal denervation (DNX) was developed in dogs by rapidly injecting 6-hydroxydopamine (6-OHDA) into the renal artery with simultaneous collection of the venous effluent to avoid systemic effects. The procedure induced a 93.1 ± 2.7% destruction of the adrenergic innervation as assessed by a histochemical fluorescence technique. A comparative study of both kidneys was carried out 3 days after DNX. Renal blood flow (RBF) and its cortical distribution were measured with radioactive microspheres at mean perfusion pressures of 117 mmHg (1 mmHg = 133.322 Pa) (normotension) and 70 mmHg (hypotension). The comparison of renal perfusion between kidney halves revealed a remarkable perfusion symmetry during normotension and hypotension in both the intact and the DNX kidney. Renal DNX by 6-OHDA did not alter RBF when the kidneys were perfused at normotension. During hypotension, RBF fell by 45% on the control side, while a nonsignificant decrease was noted in the DNX kidney. The redistribution of blood flow to inner cortical zones was less marked in the DNX side during hypotension. The DNX kidney did not release renin during normotension, but exhibited a normal renin response to hypotension. These data are partly in agreement with classical denervation models, and indicate that (1) denervation by 6-OHDA protects renal perfusion during hypotension; and (2) the redistribution of blood flow to inner cortical nephrons is independent of release of renin, but modulated by adrenergic innervation.
Parathyroidectomy significantly decreases hypertension in spontaneously hypertensive and deoxycorticosterone plus saline treated rats
Authors: Gairard Alexis , Berthelot Alain , Schleiffer René , Pernot Fanny
Published: April 2011

In male Sprague–Dawley rats, hypertensive development was diminished for 10 weeks when parathyroidectomy (PTX) was performed 1 week before deoxycorticosterone plus saline (DOCA + NaCl) treatment. In young spontaneously hypertensive male rats (SHR, Okamoto strain) parathyroidectomy performed after weaning lessened hypertensive levels and lowered heart rate for 24 weeks. When mineralocorticoid or genetic hypertension was established, parathyroidectomy did not significantly change blood pressure levels. High dietary calcium in PTX–SHR rats reestablished normal serum calcium but not systolic blood pressure to the level of sham SHR. From our present and previously reported results, it appears that the parathyroid gland is necessary for the total development of hypertension in both models.
Activation heat and latency relaxation in relation to calcium movement in skeletal and cardiac muscle
Authors: Mulieri Louis A. , Alpert Norman R.
Published: April 2011

Measurements of activation heat, initial heat, twitch tension, and latency relaxation were made using thin-layer, vacuum-deposited thermopiles and isometric force transducers, respectively. Experiments were performed on frog skeletal muscle fiber bundles and on rabbit right ventricular papillary muscles at 0, 15, and 21 °C in normal and 1.75× to 2.5× mannitol hyperosmotic bathing solutions. In skeletal muscle, activation heat, obtained by stretching to zero overlap, was only slightly affected by 1.75× hyperosmotic solution and consisted of a fast and a slow component. Both components have a refractory period and a relatively refractory period which can be demonstrated by double pulse stimulation. The twitch potentiators Zn2+ and caffeine increase the total activation heat and the magnitude and rate of the fast component. The temporal relation between the latency relaxation and activation heat is demonstrated. The latency relaxation is independent of the number of sarcomeres in series in a muscle. Activation heat and latency relaxation records from heart muscle are obtained in 2.5× hyperosmotic bathing solution. A model of excitation–contraction coupling is presented which indicates that (1) the downstroke of the latency relaxation monitors the functioning of the Ca2+ -permeability or debinding mechanism in the terminal cisternae, (2) the fast component of activation heat monitors the amount of Ca2+ bound to troponin C, and (3) the total amplitude of activation heat is a measure of the total quantity of Ca2+ cycled in a twitch.
The role of superficially bound calcium in the regulation of myocardial contractility and the positive inotropic response to ouabain
Authors: Bailey Leslie E. , Fawzi Ahmad B.
Published: April 2011

Positive inotropic effects induced in hearts by paired pacing and ouabain treatment were found to be dependent on the content of calcium in a superficial pool, Ca1. Two possible mechanisms for the expansion of this pool were investigated in isolated cardiac myocytes in which the cell surface structures were preserved from proteolytic digestion. Guinea pig ventricles were disrupted mechanically to obtain intact myocardial cells. The cell yield from this preparation was enriched by incubation with Cytodex® beads and the characteristics of calcium binding to the cell–bead suspension were determined by continuous flow equilibrium dialysis. Scatchard plots revealed two components for calcium binding; a high affinity (KA ~ 65 mM−1) and a low affinity (KA ~ 140 M−1) pool. Ouabain (10−9 to 10−6 M) increased, in a dose related manner, the KA for calcium binding to the low affinity sites without affecting the total number of binding sites. The calculated amount of calcium bound to the low affinity pool at [Ca]e = 1.8 mM was closely correlated with the positive inotropic effect (PIE) measured in guinea pig hearts perfused with the same calcium concentration. At [Ca]e = 0.45, 0.9, or 3.6 mM, the response to ouabain (1 × 10−7 and 5 × 10−7 M) was greater than expected on the basis of the increase in calcium binding to the low affinity sites. The results suggest that at least one event in the inotropic response to ouabain involves increased affinity for calcium binding to low affinity sites on the cell surface, but that the increase in calcium bound at any [Ca]e is insufficient to produce the PIE directly.
Dipalmitoyl phosphatidylcholine dissolved in ethanol forms highly elastic monolayers
Authors: Seufert Wolf D. , Lachiver Gérard , Bessette France
Published: April 2011

Small quantities of pure dipalmitoyl phosphatidylcholine dissolved in ethanol form highly elastic monolayers at an air – water interface. We submit that such preparations, administered as aerosols, could rapidly replace a missing or functionally deficient monolayer of natural surfactant in the lungs.
Reduction of occlusive coronary artery thrombosis and myocardial ischemia by molsidomine in anesthetized dogs
Authors: Fiedler Volker B.
Published: April 2011

The antianginal drug molsidomine was evaluated for its in vivo antithrombotic effects in barbiturate-anesthetized open-chest dogs by inducing left circumflex (LCX) coronary artery thrombosis with low-amperage stimulation (150 μA for 6 h) of the intimal surface of the vessel. Intravenous bolus administration of 0.10 mg/kg molsidomine 10 min prior to onset of electrical stimulation partially prevented occlusive LCX thrombosis and prolonged time to complete vessel occlusion by 45 min (p < 0.05). Intracoronary thrombus mass was reduced (14 ± 0.8 vs. 32 ± 4 mg in controls, p < 0.05). Final 6-h infarcts after complete LCX coronary artery thrombosis were measured by triphenyltetrazolium chloride (TTC) staining and were smaller after molsidomine pretreatment when related to left ventricular mass (14 ± 3 vs. 28 ± 2%, p < 0.02) or to the LCX vessel area at risk for infarction (18 ± 3 vs. 58 ± 4%, p < 0.01). Molsidomine did not induce hemodynamic alterations during time to complete thrombotic LCX coronary artery occlusion. In saline controls, heart rate and end-diastolic pressure increased whereas blood pressure and contractility decreased significantly. The percentage of ventricular ectopic beats concomitant to thrombus formation and myocardial ischemia was significantly reduced in the drug-treated dogs. Molsidomine also partially prevented the reduction in myocardial function parallel to blood flow diminution as measured with an ultrasonic technique. The drug further exerted significant ex vivo inhibition of collagen-induced platelet aggregation (p < 0.01 vs. control from 4 h after onset of LCX stimulation). In addition to established hemodynamic effects of molsidomine there may also be a direct effect on platelet aggregation and thrombus formation in vivo which delays coronary artery narrowing and occlusion as one primary cause for myocardial ischemia.
Glycyl-L-leucine transport in the rat small intestine
Authors: Cheeseman C. I. , Johnston G.
Published: April 2011

The uptake of the peptide glycyl-L-leucine across the brush border of the rat small intestinal enterocyte was studied using everted rings. The transfer of leucine from the dipeptide into the enterocyte was greater than the glyeine uptake from glycyl-L-leucine. This additional component for leucine transport was found to be abolished by the removal of sodium, by the presence of 10 mML-alanine β-naphthylamide, and by excess free leucine. In contrast, the uptake of glycine from glycyl-L-leucine was not sodium-dependent and was not reduced by the presence of excess free leucine. The presence of harmaline over a concentration range up to 10 mM inhibited some of the peptide-bound leucine and glycine uptake. Transport of leucine from glycyl-L-leucine in the presence of 20 mM free leucine was competitively inhibited by glycyl-L-prolinc, although not completely. It is concluded that, in the rat, the sodium-sensitive component of amino acid uptake from the dipeptide represents free amino acid liberated by superficial hydrolysis, while the transport of the intact peptide is not sodium dependent. In addition, it appears that there are at least two routes of entry for the intact dipeptide glycyl-L-leucine, only one of which is shared with glycyl-L-proline.
Cardiovascular effects of thoracic afferent nerve stimulation in conscious dogs
Authors: Armour J. A. , Pace J. B.
Published: April 2011

Afferent stimulation of a severed thoracic autonomic nerve in 18 conscious dogs produced in 13 instances hypertension and in 5 instances hypotension. Reflex hypertension was usually accompanied by augmented atrial and ventricular force of contraction. The hypertension could be maintained for over 5-min duration by constant stimulation. Inotropic changes accompanying this hypertension were accentuated following atropine administration and abolished by propranolol. Blood pressure changes following atropinization were initially augmented. On the other hand reflex hypotension was accompanied by bradycardia and decreased atrial contractility. These changes were essentially abolished by atropine. Afferent nerve stimulation with frequencies as low as 1 Hz initiated reflex changes. Maximal responses were obtained by stimulation frequencies of 10–15 Hz. It is concluded that significant and relatively sustained cardiovascular reflexes can be generated by stimulation of cardiac afferent nerves in conscious dogs.
Physiological conditions for the study of basal and meal stimulated exocrine pancreatic secretion in the dog. Absence of feedback inhibition of basal secretion
Authors: Diaz G. Roblès , Devaux M. A. , Johnson C. D. , Adrich Z. , Sarles H.
Published: April 2011

Pancreatic secretion has been studied in dogs in basal and postprandial conditions, as nearly physiological as possible. When pancreatic juice was excluded from the duodenum pancreatic secretion was not raised. compared with secretion during the return of juice to the duodenum. In fact, in seven mongrels, returning pancreatic juice led a transient rise in pancreatic secretion. This was not seen in five beagles. These results indicate that dogs do not manifest the feedback control of pancreatic secretion by pancreatic juice observed in other species. Pancreatic secretory activity was determined in 10 dogs after stimulation by food. The highest secretion rates occurred during the initial 60 min. The maximal secretion of protein occurred before the maximal secretion of fluid and bicarbonate. The effect of the meal diminished slowly during the subsequent minutes but did not reach basal levels after 2 h. In physiological conditions, maximal pancreatic secretion of fluid and bicarbonate was about one-fifth and of protein was almost one-seventh of the maximal secretory capacity obtained with secretin and cholecystokinin, respectively. Potential specific activity of trypsinogen was unchanged during the different experimental conditions. Trypsinogen output represented a constant average of 20% of protein output. The interindividual variability of pancreatic secretion rates was reduced when outputs were expressed per kilogram of body weight. In general, a significant positive correlation was found between body weight and the secretory outputs. No differences were observed in the response of mongrel and beagle dogs to a meal.
Effect of efferent denervation of the vagus nerve on nonadrenergic inhibitory responses obtained from the rat stomach in vitro
Authors: Huggins N. , Cook M. A.
Published: April 2011

The possibility that antidromic stimulation of afferent nerves is involved in the mediation of nonadrenergie inhibitory (NAI) responses obtained from isolated preparations was tested using the isolated rat stomach – vagus nerve preparation. Unilateral supranodose vagotomies 7 – 21 days prior to obtaining the preparations permitted efferent denervation to occur and the responses obtained in vitro from stimulation of the sectioned nerves were compared with those from the control nerves. Supranodose vagotomy abolished the responses obtained from the preparations while stimulation of the control nerves gave rise to normal biphasic responses consisting of both excitatory and NAI components. Histological examination of the nodose ganglia revealed the presence of normal sensory ganglion cells while abundant intact axons were observed in nerve trunks on the lesioned side. It is concluded that afferent nerves in the vagus are not involved in the mediation of NAI responses obtained from the rat stomach in vitro.
Chemical and biochemical aspects of superoxide radicals and related species of activated oxygen
Authors: Singh Ajit
Published: April 2011

The spectrum of biological processes in which oxygen is used by living systems is quite large, and the products include some damaging species of activated oxygen, particularly the superoxide radical [Formula: see text] and hydrogen peroxide (H2O2). Superoxide radicals and hydrogen peroxide, in turn, can lead to the formation of other damaging species: hydroxyl radicals (∙OH) and singlet oxygen (1O2). Hydroxyl radicals react with organic compounds to give secondary free radicals that, in the presence of oxygen, yield peroxy radicals, peroxides, and hydroperoxides. Formation, interconversion, and reactivity of [Formula: see text] and related activated oxygen species, methods available for their detection, and the basis of their biological toxicity are briefly reviewed.
Concluding remarks: a prospective view of active oxygen in medicine
Authors: Petkau A.
Published: April 2011

Factors are identified that influence the initiation, propagation, and efficiency of free-radical processes, or that ameliorate or mask them. Major biochemical disruptions of the ischemic myocardium or the central nervous system are cited for their underlying free-radical reactions. Encouraging attempts at rational therapy of disease having a free-radical component are referenced.
Growth hormone stimulates serotonin secretion into the hepatic portal circulation
Authors: Hussain M. N. , Sirek A. , Dvorak M. , Cukerman E. , Sirek O. V.
Published: April 2011

Hepatic portal plasma concentrations of free serotonin were found to be transiently but significantly elevated in normal dogs following a single injection of ovine growth hormone into a peripheral vein. The data are consistent with the concept that spike concentrations of growth hormone are capable of altering the splanchnic concentration of agents that are concerned with glucose homeostasis.
Effects of phenoxybenzamine, metoprolol, captopril, and meclofenamate on cardiovascular function in deoxycorticosterone acetate hypertensive Yucatan miniature swine
Authors: Ciccone Charles D. , Zambraski Edward J.
Published: April 2011

Eight adult Yucatan miniature swine were implanted with deoxycorticosterone acetate (DOCA) impregnated silicone strips (100 mg∙kg−1). After 16 weeks of DOCA treatment mean arterial pressure (MAP) increased to 183 ± 4 mmHg (1 mmHg = 133.322 Pa). In four normal animals arterial pressure was 126 ± 8 mmHg. The increase in MAP in the DOCA animalas was due to an elevated total peripheral resistance (TPR) with cardiac output remaining normal. In tests with conscious animals, phenoxybenzamine (1 mg∙kg−1) significantly decreased arterial pressure via a selective decrease in TPR. Neither meclofenamate, metoprolol, nor captopril affected MAP in these DOCA hypertensive animals. Dose–response curves to exogenous norepinephrine and angiotensin II revealed that the DOCA animals had an increased pressor sensitivity to both of these agents. These data suggest that in the DOCA hypertensive Yucatan swine an increase in alpha adrenergic activity and (or) an increase in smooth muscle responsiveness to circulating catecholamines is responsible for the increase in blood pressure as a result of an increase in total peripheral resistance.
The effect of alloxan- and streptozotocin-induced diabetes on calcium transport in rat cardiac sarcoplasmic reticulum. The possible involvement of long chain acylcarnitines
Authors: Lopaschuk Gary D. , Katz Sidney , McNeill John H.
Published: April 2011

Isolated working hearts from diabetic rats have a decreased ability to respond to increasing preload or afterload. The ability of cardiac sarcoplasmic reticulum to transport Ca2+ was examined in diabetic rats. Hearts were obtained from female Wistar rats 120 days or 7 days after the induction of diabetes by a single I.V. injection of either alloxan (65 mg/kg) or streptozotocin (60 mg/kg). At all Ca2+ concentrations tested (0.2–5.0 μM free Ca2+) cardiac sarcoplasmic reticulum from 120-day diabetic rats showed a significant decrease in the rate of ATP-dependent tris-oxalate facilitated Ca2+ transport (62–73% of control). This was accompanied by a decrease in Ca2+ ATPase activity. The levels of long chain acylcarnitines associated with the microsomal sarcoplasmic reticulum preparation from 120-day diabetic rats were significantly higher than those present in sarcoplasmic reticulum from control rats. Palmitylcarnitine, the most abundant of the long chain acylcarnitines, in concentrations < 7 μM was found to be a potent time-dependent inhibitor of Ca2+ transport in both control and diabetic rat sarcoplasmic reticulum preparations; inhibition of Ca2+ transport was found to be more marked in the control preparations. This would indicate that a degree of inhibition produced by the high endogenous levels of palmitylcarnitine may already be present in the diabetic rat preparations. Cardiac sarcoplasmic reticulum prepared from acutely diabetic rats (7 days) did not show any decrease in Ca2+ transport ability. Levels of long chain acylcarnitines associated with the microsomal preparation enriched in sarcoplasmic reticulum were also unchanged. These findings suggest that the alteration in heart function in 120-day diabetic rats may be due to the buildup of cellular long chain acylcarnitines which inhibit sarcoplasmic reticulum Ca2+ transport. The absence of any change in Ca2+-transport activity or levels of long chain acylcarnitines at 7 days suggests that the alterations seen in 120-day diabetic rats must be of gradual onset.
Effect of glucocorticoid administration in vivo on insulin binding in rat testis
Authors: Saucier Johanne , Dubé Jean Y. , Tremblay Roland R.
Published: April 2011

We have studied the effects of adrenalectomy and glucocorticoid injections on insulin binding in membranes from rat testis and liver. Glucocorticoids were administered for 7 days to adrenalectomized rats at daily doses of 30 or 300 μg for dexamethasone and 100 or 1000 μg for prednisolone. Glucocorticoids, at the selected doses, were associated with 5- to 10-fold increases in basal insulin levels with no significant changes in glucose concentrations. As previously shown by other studies, down-regulation of insulin receptors was observed in liver membrane particularly at the higher dose of steroids. Such an effect was not found in the testis. By contrast, the number of high-affinity sites in the testis was slightly increased with the higher doses of dexamethasone and prednisolone. However, percent 125I-labelled insulin binding was not significantly changed after corticotherapy. These results are in accord with our previous studies and suggest that the testicular receptor for insulin is not affected by mild to moderate changes of insulin concentrations, but that it can be modulated by glucocorticoids through other mechanisms.
Comparison of infarct size produced by coronary artery occlusion in purebred beagle and mixed-breed dogs
Authors: Burmeister William E. , Reynolds Robert D.
Published: April 2011

This investigation demonstrated a significant difference in infarct size following coronary artery occlusion between purebred beagles and mixed-breed dogs. Myocardial infarctions were produced by a two-stage ligation of the left anterior descending artery (LAD). Myocardial infarct size, expressed as percent of left ventricular mass, was determined at 24 h by nitro blue tetrazolium staining. Infarct size was significantly smaller (12.5 ± 3.4%) and more variable (coefficient of variation 72%) in beagles than in mixed-breed animals (28.0 ± 2.4% infarct size, 23%; coefficient of variation) (p < 0.001). Ectopic activity at 24 h was similar for both beagles and mixed breed, 92 ± 7 and 92 ± 2% of total heart rate, respectively. Thus this study indicates that the breed of dog (i.e., purebred beagles versus mixed-breed animals) can be an important variable in the study of infarct size resulting from coronary artery occlusion.
A comparative study of the acute effects of cetamolol (AI-27,303), atenolol, propranolol, and dexpropranolol on blood pressure, sympathetic nerve and ganglion activity of cats
Authors: Jaramillo J.
Published: April 2011

The effects of cetamolol (AI-27,303, Betacor®), atenolol, propranolol, and dexpropranolol were evaluated in 36 chloralose–urethane anesthetized cats. Blood pressure, sympathetic nerve discharge, and ganglionic activity (from the superior cervical ganglion) were recorded after the intravenous administration of 2.5, 5.0, and 10 mg/kg doses of the compounds. The results indicate that cetamolol and atenolol decreased blood pressure and discharge in the postganglionic sympathetic nerve and impaired transmission at the level of sympathetic ganglia. Propranolol and dexpropranolol given at the same doses produced a larger decrease in blood pressure, but increased the sympathetic discharge and had no effect on ganglionic spike amplitude.
Effects of atrial natriuretic factor on renal handling of water and electrolytes in rats
Authors: Keeler R. , Azzarolo Ana Maria
Published: April 2011

The intravenous injection of an extract of atrial myocardium into anesthetized rats during a hypotonic diuresis resulted in an increase in the renal excretion of water, sodium, potassium, calcium, magnesium, and phosphate. There was an increase in urine concentration which was probably a result of the secretion of vasopressin since it did not occur in Brattleboro (di/di) rats. A transient increase in glomerular filtration rate and renal plasma flow occurred during the first five minutes with a more sustained rise in filtration fraction. Injection of atrial extract also caused a partial inhibition of solute-free water formation in Brattleboro rats subjected to water diuresis and a partial inhibition of solute-free water reabsorption in rats subjected to maximal antidiuresis by infusing vasopressin. In neither case was the degree of inhibition as profound as that observed after injecting furosemide in a dose which caused a comparable natriuretic response. A large dose of furosemide blocked the natriuretic response to atrial extracts whereas, when a comparable level of sodium and water output was produced by massive infusions of saline, the natriuretic response to atrial extract was increased. It is suggested that atrial natriuretic factor might inhibit sodium transport in nephron segments beyond the medullary thick ascending limb. Furosemide might also act at the same tubular site or inhibit' tubular secretion of the atrial natriuretic factor.
The effects of food deprivation on β-adrenergic responsiveness in male rats
Authors: Barney Christopher C. , Rutt Daniel A. , Katovich Michael J.
Published: April 2011

Male rats were deprived of food for varying lengths of time (0–96 h) and their responses to β-adrenergic stimulation with isoproterenol were tested. Food deprivation for 48 or 96 h attenuated the increase in tail skin temperature normally seen following administration of isoproterenol. The degree of attenuation was dependent on the duration of the deprivation period. Rats deprived of food for 96 h and then refed for 48, 96, or 144 h showed a return of tail skin temperature response to near normal levels. The increase in heart rate observed following administration of isoproterenol was also attenuated following 48 or 96 h of food deprivation. Again, the degree of attenuation was dependent on the duration of the deprivation period. Food deprivation for 96 h led to a decrease in basal plasma levels of T3, T4, and glucose. The increase in plasma glucose following administration of isoproterenol was also attenuated following 96 h of food deprivation. In contrast to the thermal, cardiac, and glucose responses, the dipsogenic response to isoproterenol was increased following food deprivation. The attenuation in β-adrenergic responses observed in the food-deprived rats might help explain the effects of food deprivation on cold tolerance.
Freezing point and melting point of barnacle muscle fibers
Authors: Caillé Jean-Pierre
Published: April 2011

The freezing point and the melting point of myoplasm were measured with two experimental models. In all samples, a supercooled stage was reached by lowering the temperature of the sample to approximately −7 °C, and the freezing of the sample was mechanically induced. The freezing process was associated with a phase transition in the interstices between the contractile filaments. In intact muscle fibers, the freezing point showed a structural component (0.43 °C), and the melting point indicated that the intracellular and the extracellular compartments are isotonic. When the sample of myoplasm, previously inserted in a cylindrical cavity was incubated in an electrolyte solution, the freezing point showed a structural component similar to that of the intact muscle fiber, but the melting point was lower than the freezing and the melting points of the embedding solution. This was interpreted as evidence that the counterions around the contractile filaments occupied a nonnegligible fraction of the intracellular compartment.