bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenomedullary secretory response to midbrain stimulation in rat: effects of depletion of brain catecholamines or serotonin
Authors: Gauthier Pierre , Reader Tomas A.
Published: April 2011

Electrical stimulation of the periaqueductal gray substance (PAG) of the rostral midbrain of the rat produced biphasic or monophasic pressor responses depending on the duration of the stimulus train. Marked increases in plasma noradrenaline (NA) and adrenaline (A) levels accompanied the pressor responses, indicating the participation of the adrenal medulla. Depletion of central catecholamines (CA) by intraventricular administration of 6-hydroxydopamine (6-OHDA) did not affect the primary vasomotor component but markedly depleted adrenal CA levels and attenuated the adrenomedullary component of the response to brain stimulation. The intraperitoneal administration of p-chlorophenylalanine (pCPA) not only depleted brain serotonin (5-HT) levels but also reduced brain CA levels significantly. The adrenaline (A) levels were reduced in the adrenal glands of these rats and the adrenal secretory response to brain stimulation was attenuated. In contrast, the selective destruction of central 5-HT neurons by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) in rats pretreated with desmethylimipramine (DMI) did not influence either the pressor nor the plasma CA responses to brain stimulation. Furthermore, the adrenal glands of these rats were normal. The results suggest that: (i) the central catecholaminergic neurons play an important role in the regulation of the adrenal glands but are not essential for the activation of the sympathetic vasoconstrictor fiber system; (ii) the pressor and plasma CA responses to PAG stimulation are not dependent on the central serotonergic system.
Depth distribution and mechanism of changes in extracellular K+ and Ca2+ concentrations in the hippocampus
Authors: Krnjević K. , Morris M. E. , Reiffenstein R. J. , Ropert N.
Published: April 2011

In the CA1 area of the hippocampus of urethane-anaesthetized rats, the greatest Δ[K+]o and Δ[Ca2+]o evoked by repetitive fimbrial – commissural stimulation were always found in the pyramidal cell layer; but there were large increases in [K+]o over a wide range of depth, whereas a major fall in [Ca2+]o was localized almost exclusively to the level of the pyramidal layer. A sustained focal negative potential was also evoked by fimbrial stimulation; it resembled Δ[K+]o in time course and depth distribution and therefore probably reflected cellular depolarization caused by increased [K+]o. The close correlation between Δ[Ca2+]o and Δ[K+]o and the appearance of population spikes (especially in bursts of three to four spikes) indicate that pyramidal cell firing and corresponding K-outward and Ca-inward currents are mainly responsible for the accumulation of [Formula: see text] and the depletion of [Formula: see text]. In CA3 pyramidal areas, Δ[K+]o and Δ[Ca2+]o were comparable in magnitude and distribution to changes seen in CA1, but they occurred after a longer latency, and the major Δ[Ca2+]o had a longer duration, consistent with a more prolonged Ca2+ current.
Muscarinic receptors in guinea pig ileum. A study by agonist – 3H-labelied antagonist competition
Authors: Jim K. , Bolger G. T. , Triggle D. J. , Lambrecht G.
Published: April 2011

A series of muscarinic agonists (n = 18) derived from dioxolane, furan, piperidine, and thiacyclohexane ring structures which have a degree of conformational restraint have been examined in guinea pig ileal smooth muscle. Binding to muscarinic receptors was determined by competition with 3H-labelled (−)-quinuclidinyi benzilate. Agonist binding was characterized by shallow displacement curves and Hill coefficients (nH) of <1. Binding (K1,) was resolved into high (K1) and low (K2) affinity components. Correlations between drug – receptor binding and pharmacological activity were examined. A good correlation was found between K1 and K2 (pK1 = 1.33 × pK2 − 0.1), suggesting that the structural requirements for binding at low and high affinity sites are similar. Good correlations also exist between pK1 and pD2 (pK1 = 0.63 × pD2 + 1.27, furans and dioxolanes; pK1 = 0.71 × pD2 + 1.30, piperidines and thiacyclcohexanes) confirming that a pharmacologically potent agonist has a high binding affinity. Although K1 represents only an "average" binding affinity its correlaiton with pD2 is better than those between pK1 or pK2 and pD2. The significance of these several correlations is discussed and some general limitations to the correlation of binding and response data at pharmacological receptors are noted.
Inhibition of fast axonal transport in vitro by tetracaine: an increase in potency at alkaline pH, and no change in potency in calcium-depleted nerves
Authors: Lavoie P.-A.
Published: April 2011

Some of the present in vitro experiments compare the degree of inhibition of fast axonal transport produced by tetracaine at neutral and at alkaline pH. In desheathed spinal nerves from bullfrog, 0.5 mM tetracaine reduced the quantity of [3H]leucine-labeled proteins which were transported to a ligature by 43% at pH 7.2 and by 96% at pH 8.2; separate experiments established that transport was not affected by the pH change in the absence of tetracaine. The relationship between pH and transport-blocking potency of tetracaine (pKa 8.2) is such that the local anesthetic is more potent when more uncharged form of the molecule is present; this may reflect the easier penetration across the axonal plasma membrane by the uncharged form of the tetracaine molecule. The axonal smooth endoplasmic reticulum has been attributed the function of a calcium reservoir, and it appeared possible that local anesthetics could block axonal transport by releasing calcium from this structure. However, the inhibition of transport produced by 1 mM tetracaine (pH 7.1) in sheathed nerves was approximately 80% both in nerves with a lower than normal calcium content (47% of normal) and in nerves with a normal calcium content; this result does not support the hypothesis that inhibition of axonal transport by local anesthetics is mediated by an increase in intracellular free Ca2+, but does not rule out the hypothesis either.
Rabbit atrial histamine receptors and cyclic AMP
Authors: Longhurst Penelope A. , McNeill John H.
Published: April 2011

The present study confirms the presence of H2 receptors in rabbit right and left atrium by measuring changes in cyclic AMP. Histamine produced significant increases in cyclic AMP in both atria although the increases were less in left atria. Since H2 receptors are always associated with the adenylate cyclase – cyclic AMP system, the data provide further support for the suggestion that H2 receptors exit in rabbit right and left atria.
Chloride removal selectively inhibits phasic contractions of guinea pig ileal longitudinal smooth muscle
Authors: Rangachari P. K. , Triggle C. R. , Daniel E. E.
Published: April 2011

Removal of external chloride selectively and reversibly inhibits the phasic responses of the guinea pig ileal longitudinal muscle to high potassium and cholinergic stimulation. The binding of calcium to a relatively superficial pool is affected by chloride removal. Alterations in anionic composition of bathing solution affects the availability of calcium for excitation–contraction (E–C) coupling in smooth muscle.
Nutrition and hypertension
Authors: Mogenson Gordon J. , Box Blanche M. , Philbrick Diana J.
Published: April 2011

There has been a good deal of interest in the relation of nutrition to cardiovascular diseases and this is likely to continue. We consider recent research developments concerned with the well known examples of the association of high salt intake with hypertension and of saturated fats with atherosclerosis. Some of the difficulties encountered in the investigation of dietary factors in hypertension are similar to those encountered in the investigation of dietary factors in atherosclerosis and coronary heart disease. Much additional research, which takes into account the multifactorial nature of cardiovascular disease, is needed to determine the effects of diet on the development and treatment of these diseases.
Nutrition and immune responses
Authors: Chandra R. K.
Published: April 2011

Clinical and epidemiologic data suggest a causal relationship between nutritional deficiency and infection. Among other factors, impaired immune responses secondary to malnutrition increase susceptibility to infectious illness. Protein-energy undernutrition and deficiencies of iron, zinc, pyridoxine, and other nutrients depress a variety of immunity functions. Cell-mediated immunity, complement system, microbicidal activity of phagocytes, secretory antibody response, and antibody affinity are often decreased. Recent studies have revealed many metabolic and hormone alterations as well as changes in the number and function of lymphocyte subpopulations. Obesity also is associated with impaired cellular immune functions. Dietary factors may play a critical role in host resistance to disease.
Periodicities in respiration and heart rate in newborns
Authors: Finley John P. , Nugent Sherwin T.
Published: April 2011

Periodic breathing is common in normal infants, but may be associated with prolonged apnea leading to crib death. The mechanisms of periodic breathing and its relation to normal breathing patterns are unclear. We recorded respiratory and heart rate (HR) patterns of 11 healthy newborn infants during quiet sleep, in both normal and periodic breathing. Spectral analysis of the respiratory pattern revealed a low-frequency (LF) periodicity in normal breathing approximately equal to the frequency of periodic breathing when this occurs. Periodic breathing thus appears to be an exaggeration of an underlying slow amplitude variation which is present in regular breathing. LF periodicity also appeared in the HR pattern in both normal and periodic breathing, suggesting an LF modulation of cardiovascular control as well. The lack of a definite phase relation between HR and ventilation at LF may indicate dominant peripheral, rather than central, interactions between HR and respiration at these frequencies.
A comparative study of collagenase- and trypsin-dissociated embryonic heart cells: reaggregation, electrophysiology, and pharmacology
Authors: Colizza Diane , Guevara Michael R. , Shrier Alvin
Published: April 2011

The electrophysiological and pharmacological properties of aggregates prepared from cells of 7-day-old chick embryo heart ventricles depend on the enzyme used for cell dissociation. The mean beat rate of aggregates formed from trypsin-dissociated cells was about 53 beats/min whereas aggregates formed from collagenase-dissociated cells had a mean beat rate of more than twice this value. Spontaneous activity of most aggregates formed from trypsin-dissociated cells was inhibited by elevating external potassium or by adding tetrodotoxin to the medium. A similar response to potassium was seen in all aggregates formed from collagenase-dissociated cells. However, approximately half of the aggregates formed from collagenase-dissociated cells were tetrodotoxin insensitive. Intracellular microelectrode recordings demonstrated that aggregates formed from collagenase-dissociated cells typically had reduced action potential maximal upstroke velocities and depolarized threshold potentials in comparison to those recorded from aggregates formed from trypsin-dissociated cells. In the presence of tetrodotoxin the maximal upstroke velocity of aggregates formed from either collagenase- or trypsin-dissociated cells decreased markedly. In the case of the collagenase-treated cells, the spontaneous activity which persisted in the presence of tetrodotoxin was abolished by the slow channel blocker D-600. Computer simulation of membrane depolarization supports the view that aggregates formed from collagenase-treated cells have a reduced fast inward sodium current and a significant leakage current. Aggregates prepared from trypsin-dissociated cells display properties which more closely resemble those of intact 7-day embryonic ventricular tissue. We therefore conclude that, contrary to previous reports, collagenase is not the enzyme necessarily best suited for cell dissociation in all tissue culture studies.
Δ9-Tetrahydrocannabinol and cannabidiol: dose-dependent effects on evoked potentials in the hippocampal slice
Authors: Kujtan P. W. , Carlen P. L. , Kapur B. M.
Published: April 2011

The effects of (−) trans-Δ9-tetrahydrocannabinol (THC) and its metabolite cannabidiol (CBD) were investigated on evoked responses in the CA1 and dentate gyrus regions of the guinea pig transverse hippocampal slice. In both areas orthodromically evoked responses were enhanced by 10−7 M THC, while 10−6 M THC caused depression. Antidromic responses were not significantly affected. Antidromically-evoked inhibition in the CA1 region was decreased at low doses and unaffected at higher doses, while the facilitation by orthodromic interaction was unaffected at both dose ranges. The early part of the orthodromic field potential corresponding to the excitatory postsynaptic potential (EPSP) was enhanced at 10−7 M in both areas. CBD (10−6 M) decreased facilitation in CA1, and caused delayed excitation in the dentate granule layer. This study supports the conclusion that the biphasic effects of THC are dose dependent.
Synaptic transmission in thoracic autonomic ganglia of the dog
Authors: Armour J. A.
Published: April 2011

Afferent stimulation of one canine thoracic cardiopulmonary nerve can generate compound action potentials in another ipsilateral cardiopulmonary nerve. These compound action potentials persist after acute decentralization of the middle cervical ganglion, indicating that they result from neural activity in the middle cervical ganglion and thoracic nerves. Changing the frequency of stimulation can alter the compound action potentials, suggesting that temporal facilitation or inhibition occurs in this middle cervical ganglion preparation. The compound action potentials can be modified by stimulation of sympathetic preganglionic fibers and by hexamethonium, atropine, phentolamine, propranolol, and (or) manganese. It thus appears that afferent cardiopulmonary nerves can activate efferent cardiopulmonary nerves via synaptic mechanisms in the stellate and middle cervical ganglia. It also appears that these mechanisms involve adrenergic and cholinergic receptors and are influenced by preganglionic sympathetic fibers arising from the cord.
Effects of step changes in pH on isometric tetanic tension of toad sartorius muscle
Authors: Renaud J. M. , Stevens E. Don
Published: April 2011

The effect of a rapid change in pHe (pH of bathing solution) on the isometric tetanic tension developed by sartorius muscles of toads acclimated to 5 and 25 °C was measured at 5 and 25 °C. The pH was altered by changing the carbon dioxide concentration of a bicarbonate buffered physiological solution. Acclimation temperature did not modify the response to a rapid change in pH, but test temperature did. Following a pH decrease from 9.0 to 6.0, tetanic tension decreased at a faster rate at 5 °C than at 25 °C. A new steady state was reached in 15 min at 5 °C but in 40 min at 25 °C. Following a pH increase from 6.0 to 8.5, tetanic tension increased at a faster rate at 25 °C than at 5 °C. A new steady state was reached in 60 min at 5 °C but in 10 min at 25 °C. We conclude that the rate of carbon dioxide diffusion through the sartorius muscle is only one factor that determines how rapidly tetanic tension changes following the step change in pH, and that muscle resists pH change more effectively at higher temperatures.
Measurement of red cell sickling: a method for studying the efficacy of antisickling drugs under physiological conditions
Authors: Ohnishi S. Tsuyoshi , Hashimoto Koji , Sato Takashi
Published: April 2011

A method was developed to study sickling in vitro under physiological conditions using a small amount of blood (0.1 mL). The diluted blood suspension (2.1 mL) was placed in a flask and flushed with a gas mixture containing 5% CO2. In deoxygenation experiments, samples were withdrawn anaerobically into a microslide (optical path 0.1 mm) and red cell morphology was studied directly under a light microscope after both ends of the microslide were sealed. The blood suspension with a hematocrit value of 1% can be deoxygenated in less than 10 min, but it takes 30 min for the sickling of cells to reach a plateau. The degree of sickling increases with increasing osmolality of the medium, or with a decrease of the pH. With a citrate–phosphate–dextrose–adenine solution, sickle blood may be stored for this type of study for about 10 days at 4 °C. The blood may be stored for about 5 days with a noncitrate preservative. This method was found useful in examining the antisickling activity of various drugs.
Structural bases for neural and myogenic control of human detrusor muscle
Authors: Daniel E. E. , Cowan W. , Daniel V. P.
Published: April 2011

The ultrastructure of normal and neurotoxin-treated human detrusor muscle was studied to define the bases for myogenic and neurogenic control and to determine the extent and selectivity of effects of the toxins. No gap junctions were observed in the 30 strips studied but there were other cell-to-cell junctions which may allow cell-to-cell coupling. Nerve varicosities in the muscle bundles were present in high frequency (9 to 15 profiles per 100 muscle cell profiles); they sometimes formed close contacts with muscle and most were bare or partly bare of glial covering. They were often present as single axons or in bundles of only a few nerves. No myelinated nerves or nerve cell bodies were seen in or near muscle bundles. This muscle seemed to be designed primarily for neural control of contractile function with single nerves innervating discrete muscle regions. Most of the nerve varicosities contained a large majority of small agranular vesicles along with some large granular vesicles, but about 20% contained a few small granular vesicles as well. The proportion of the small granular vesicles was not increased but the percentage of varicosities containing them increased slightly after treatment with 5- or 6-hydroxydopamine. Scorpion venom seriously damaged 80% of nerve varicosities, sparing no particular class, but spared axons from structural damage. Beta-bungarotoxin had similar effects. 4-Aminopyridine did not induce gap junction formation but had neurotoxic effects. These data suggest that scorpion venom is a useful tool to eliminate selectively physiological functions dependent on synaptic vesicles, that all nerve types contain scorpion venom binding Na channels and that the persistent atropine- and tetrodotoxin-insensitive responses of this muscle involve mechanisms independent of synaptic vesicles observable by electron microscopy. The common occurrence of multilamellar membranous structures in bladder muscle cells was reported and their origin suggested.
Vagal control of migrating motor complex-related peaks in canine plasma motilin, pancreatic polypeptide, and gastrin
Authors: Hall K. E. , Greenberg G. R. , El-Sharkawy T. Y. , Diamant N. E.
Published: April 2011

The role of the vagus nerve in the control of fasting plasma pancreatic polypeptide (PP), gastrin, and motilin levels was investigated in conscious dogs. Lowest plasma levels of motilin (81 ± 8 pmol/L), PP (19 ± 1 pmol/L) and gastrin (5 ± 1 pmol/L) were observed during phase I of the migrating motor complex (MMC). Significant peaks in plasma motilin (127 ± 11 pmol/L, P < 0.005), PP (26 ± 2 pmol/L, P < 0.005), and gastrin (14 ± 2 pmol/L, P < 0.005) were seen, coinciding with the appearance of phase II (PP and gastrin) or phase III (motilin) of the migrating motor complex in the upper gut. Whereas bilateral vagal blockade abolished the peaks in PP and gastrin, a significant (P < 0.025) increment in plasma motilin remained, which correlated with the late phase III equivalent of the vagally independent complex (VIC) in the duodenum. This VIC-related motilin peak (170 ± 20 pmol/L) was significantly higher (P < 0.025) and the time course (9 ± 2 min) significantly shorter (P < 0.01) than the peak (127 ± 11 pmol/L) and duration (31 ± 9 min) observed without vagal blockade. Thus, in fasting, the cyclical increments of PP and gastrin are both dependent on excitatory vagal innervation, whereas excitatory pathways controlling phase III associated peak motilin release are nonvagal. In addition, the pattern of fasting motilin release and the amplitude of peak motilin secretion may be affected by vagal inhibition.
Evidence for functional sodium and calcium ion channels in the membrane of cultured cardiomyocytes of the adult rat
Authors: Jacobson S. L. , Kennedy C. B. , Mealing G. A. R.
Published: April 2011

Characteristics are reported for electrical activity of adult rat cardiomyocytes in long-term primary culture. Cells in vitro for 12 to 28 days have mean membrane potential of −53 mV, are electrically excitable, and some are spontaneously contractile. The action potential of these cells has a slow rate of depolarization and is abolished by methoxyverapamil (D-600) but not by tetrodotoxin (TTX). When cells are hyperpolarized by passage of an inward current, spontaneous action potentials cease and action potentials evoked by depolarizing pulses are then TTX sensitive. Fetal bovine serum is a constituent of the culture medium. Its temporary removal causes spontaneous contractility to cease but the cells remain electrically excitable.
Parathyroid hormone (PTH) fragments relax the guinea-pig trachea in vitro
Authors: Yen Y. C. , Yang May C. M. , Kenny Alexander D. , Pang Peter K. T.
Published: April 2011

Synthetic bovine parathyroid hormone fragment containing the N-terminal 1 – 34 amino acids (bPTH-(1 – 34)) relaxed the guinea-pig trachea constricted with histamine in vitro. Peptides with bovine and human sequences purchased from Peninsula Laboratories and Beckman Bioproducts produced similar effects. Substitution of methionine in positions 8 and 18 by norleucine did not affect this property of bPTH-(1 – 34). However, when the methionines were oxidized by treating the peptide with hydrogen peroxide, the peptide could no longer produce relaxation in the trachea. Oxidation of the methionine-replaced analog did not affect the action of the peptide on the trachea. It seems that the methionines per se are not necessary, but once oxidized the conformation of the molecule may be sufficiently altered to affect its ability to relax the trachea. While propranolol can block the relaxing action of isoproterenol, this blocking agent produces no inhibition of the bPTH-(1 – 34) effect. This action of PTH on the trachea may be related to cAMP because isobutyryl-methylxanthine, a phosphodiesterase inhibitor, potentiates and imidazole, a phosphodiesterase stimulator, inhibits the trachea relaxing action of bPTH-(1 – 34).
Studies of the absorption and enterohepatic circulation of 7,12-dimethylbenz[a]anthracene in the rat
Authors: Laher J. M. , Chernenko G. A. , Barrowman J. A.
Published: April 2011

This study was undertaken to examine intraluminal factors which might alter the bioavailability of an orally ingested hydrocarbon carcinogen, 7,12-dimethylbenz[a]anthracene, and to assess the extent of its enterohepatic circulation. Rats with biliary and duodenal fistulae were administered radiolabelled hydrocarbon dissolved in olive oil, safflower oil, or medium-chain triglyceride only or with exogenous bile. Subsequent biliary excretion and plasma levels of radiolabel were monitored. Luminal bile significantly enhanced biliary recovery of radiolabel following instillation in both long-chain triglyceride vehicles, but did not affect the recovery from the medium-chain oil. In the presence of luminal bile, plasma levels and biliary recovery of radiolabel using the medium-chain triglyceride were significantly less than with either long-chain triglyceride. Following intraduodenal infusions of the radiolabelled biliary products of the carcinogen, 33% of the administered radiolabel was subsequently reexcreted in the bile within 24 h. This study, therefore, demonstrates that, while bile is not absolutely necessary for the uptake of this orally ingested hydrocarbon carcinogen, it significantly facilitates absorption from a long-chain triglyceride vehicle. Under physiological conditions, a long-chain triglyceride vehicle will provide greater systemic availability than a medium-chain vehicle for the hydrocarbon, which then undergoes extensive biliary excretion and recycling.
Cardiovascular effects of cadmium on intravenous and intracerebroventricular administration in rats
Authors: Puri V. N. , Sur R. N.
Published: April 2011

Cardiovascular responses to the intravenous (i.v.) and the intracerebroventricular (i.c.v.) administration of cadmium acetate were evaluated in rats anaesthetized with urethane. Cadmium acetate (1 mg/kg i.v.) caused an initial fall followed by a persistent rise in blood pressure. Cadmium acetate (1 μg i.c.v.) produced a more marked hypertensive effect. In the spinal-transected rat, the effect of intravenous cadmium was reduced but the effect of intraventricularly administered cadmium was completely abolished. It is, therefore, suggested that both central and peripheral mechanisms are involved in the pressor response to cadmium exposure.
1982 Borden Award Lecture: Nutritional, biochemical, and clinical aspects of inositol and phosphatidylinositol metabolism
Authors: Holub Bruce J.
Published: April 2011

Recent advances in nutritional and biochemical research have substantiated the importance of myo-inositol both as a dietary component and a constituent of cellular phosphatidylinositol. This work has indicated the importance of acyltransferase reactions for the enrichment of membrane phosphatidylinositol in arachidonic acid and the formation of the 1-stearoyl 2-arachidonoyl molecular species which commonly predominate in mammalian tissues. Inositol deficiency in animals has been shown to produce an accumulation of triglyceride in liver, intestinal lipodystrophy, and other abnormalities. Cellular functions elucidated for phosphatidylinositol in biological membranes include mediating cellular responses to external stimuli and serving as a source of arachidonic acid for the biosynthesis of prostaglandins including thromboxane. An alteration in inositol metabolism has been documented in patients with diabetes mellitus and chronic renal failure which has led to clinical interest in modulating dietary inositol levels in the prevention and treatment of human disease.
Reserpine-induced changes in cardiac adrenergic receptors
Authors: Latifpour Jamshid , McNeill John H.
Published: April 2011

Using radioligand binding techniques, the effect of reserpine pretreatment on ventricular adrenergic receptors from guinea pig was studied. [3H]Prazosin and [3H]dihydroalprenolol were used to label α1- and β-adrenergic receptors, respectively. Administration of 2.5 mg/kg reserpine for 2 days caused a significant increase in the number of β-adrenergic receptors with no effect on their affinity to respective ligands. Similar reserpine pretreatment did not affect either density or affinity of α1-adrenergic receptors for ligands. The results may explain the previous report from our laboratory in which an identical reserpine pretreatment selectively enhanced the inotropic responsiveness of the working guinea pig heart to isoproterenol.
Effect of indomethacin on fetal lung liquid formation
Authors: Cassin Sidney
Published: April 2011

Experiments were performed on seven anesthetized fetal sheep to evaluate involvement of metabolites of the cyclooxygenase system in lung liquid production. Rates of lung liquid production were determined by dye dilution technique using blue dextran. The control rate of formation of lung liquid in these preparations was 4.6 ± 0.55 mL∙kg−1∙h−1. Administration of indomethacin (1.85 mg/kg) intraarterially to fetuses resulted in a 60% decrease in the rate of formation of lung liquid. The present studies suggest an involvement of products of the cyclooxygenase system in controlling the rate of secretion of lung liquid in fetal animals.
Cetamolol: cardiovascular effects of a new cardioselective β-adrenoceptor blocker possessing partial agonistic activity and lacking membrane-stabilizing activity
Authors: Beaulieu G. , Grimes D. , Muirhead C. , Oshiro G.
Published: April 2011

The cardiovascular effects of cetamolol, a new β-adrenoceptor blocker, were studied in the anesthetized dog and cat and in the conscious dog and monkey. The compound was compared with other β-blockers known to possess various degrees of cardioselectivity, partial agonistic effects, and membrane-stabilizing activity. In the anesthetized open-chest dog, cetamolol and pindolol produced similar cardiovascular effects in that the partial agonistic activity predominated over the blockade of β-adrenoceptors. The partial agonistic activity of pindolol was greater than that of cetamolol. Unlike pindolol, cetamolol had no significant vasodilating property. However, the β-blocking effects of these two drugs predominated in the anesthetized closed-chest dog, conscious dog and monkey. Atenolol, nadolol, and propranolol, which lack partial agonistic activity, produced cardiovascular changes characteristic of this type of β-blocker in the animal preparation in which they were tested. In the anesthetized cat, comparison of the mean effective doses for the heart rate and blood pressure responses induced by isoproterenol showed that cetamolol was more cardioselective than metoprolol but less than acebutolol and atenolol. Evidence of the cardioselectivity of cetamolol was also obtained in the anesthetized closed-chest dog, although the degree of cardioselectivity of both cetamolol and atenolol was less marked than in the cat. When given orally to the conscious dog and monkey, cetamolol appeared to be well absorbed. The peak effect was observed after 1 – 2 h and persisted for the 5-h test period. It is concluded that cetamolol is a potent β-blocker with a moderate degree of partial agonistic activity and cardioselectivity in in vivo experiments.
Lack of effect of thyroid hormone on diabetic rat heart function and biochemistry
Authors: Tahiliani Arun G. , McNeill John H.
Published: April 2011

Cardiac functional abnormalities are frequently seen in diabetics and diabetes is also known to produce a state of mild hypothyroidism. To study the degree of involvement of diabetes-induced hypothyroidism on altered myocardial function, thyroid replacement therapy was carried out in streptozotocin-diabetic rats. Triiodothyronine (T3) treatment was initiated 3 days after the rats were made diabetic and was carried out for 6 weeks thereafter. Isolated perfused hearts from diabetic rats exhibited a depression in left ventricular developed pressure and positive and negative dP/dt at higher filling pressures as compared with controls. The depression could not be prevented by thyroid treatment. Calcium uptake activity in the cardiac sarcoplasmic reticulum (SR) was also depressed as a result of diabetes and this depression also was not prevented by thyroid treatment. Long chain acyl carnitine levels were found to be elevated in diabetic cardiac SR and could not be lowered by T3 treatment. The results indicate that the myocardial dysfunction observed in diabetic rats is due to factors other than the induced hypothyroidism.
A study of vasoactive intestinal peptide and acetylcholine as possible mediators of vasodilatation in the cat submandibular gland
Authors: Karpinski E. , Barton S. , Longridge D. , Schachter M.
Published: April 2011

Vasoactive intestinal polypeptide (VIP) is a powerful vasodilator agent in the submandibular gland of the cat, and its effect can be reduced by avian pancreatic polypeptide (APP), or by desensitization of the gland's blood vessels to VIP. However, the vasodilatation caused by parasympathetic nerve stimulation is not reduced by either of these means. We conclude, therefore, that VIP is unlikely to be a major mediator of this atropine-resistant vasodilatation. Experiments with a potentiator of acetylcholine, eserine, and with a depleter, suggest that acetylcholine plays some role in this vasodilatation, but it too does not appear to be the major physiological mechanism. Substance P and ATP were neither potent nor consistent vasodilators and are unlikely mediators.
Comparison of the effects of Althesin, chloralose-urethane, urethane, and pentobarbital on mammalian physiologic responses
Authors: Ching Melvin
Published: April 2011

Physiological responses to anesthetic doses of four chemically dissimilar agents, namely, Althesin, urethane, chloralose-urethane, and pentobarbital sodium were compared in rats. The tail-flick test revealed Althesin had greater antinociceptive potency than urethane, chloralose-urethane, and pentobarbital, but its duration of action was shorter than that of chloralose-urethane. Althesin produced minimal or no suppression of core body temperature and mean arterial pressure, and only moderate reduction of mean pulse pressure. The heart rate and respiratory rate of Althesin-treated rats were slower than those of chloralose-urethane and urethane-treated counterparts, respectively, but were not significantly decreased from normal controls. It is concluded that Althesin is a suitable anesthetic for short-term surgery and for studies of body temperature, heart rate, and mean arterial pressure. Because release of gonadotropin-releasing hormone into hypophysial portal blood can be observed under Althesin but is suppressed or blocked by chloralose-urethane, urethane, and pentobarbital, Althesin is the anesthetic of choice in studies concerned with the neural control of ovulatory hormone release.
Effect of exercise training on the rates of fatty acid synthesis in mice
Authors: Richard Denis , Trayhurn Paul
Published: April 2011

The present study has investigated the respective effects of training and exercise on the rates of fatty acid synthesis in mice. Male C57B1 10ScSn mice were trained by forced swimming in a tank at 36°C for 2 h each day for a 28-day period. Rates of fatty acid synthesis were determined in vivo by measuring the incorporation of tritium from 3H2O into tissue fatty acids. At the end of the training programme, both sedentary and trained mice were assigned to either exercising or resting groups. The results obtained show that both training and exercise affected the rates of fatty acid synthesis, regardless of whether the results are expressed per gram of tissue or per whole tissue. Training led to significant decreases in the rates of synthesis in the liver, interscapular brown adipose tissue, epididymal white adipose tissue, and the remaining carcass, particularly in resting mice. The rates of fatty acid synthesis in the major lipogenic tissues were also lower during exercise than under sedentary conditions. The reduction in synthesis in brown adipose tissue was noteworthy in view of the high capacity of this tissue for fatty acid synthesis. In conclusion, it is suggested that in exercise-trained mice carbohydrate is shunted away from the synthesis of lipid in favour of energy storage as glycogen.
Whole body and hindlimb cardiovascular responses of the anesthetized dog during CO hypoxia
Authors: King C. E. , Cain S. M. , Chapler C. K.
Published: April 2011

To compare with earlier studies of anemic hypoxia obtained by hemodilution, O2 carring capacity was decreased by carbon monoxide (CO) hypoxia. Arterial O2 content was reduced either 50% (moderate CO) or 65% (severe CO). In two groups of anesthetized dogs (moderate and severe CO) hindlimb innervation remained intact while in a third group (moderate CO) the hindlimb was denervated. Measurements were obtained prior to and at 30 and 60 min of CO hypoxia. Cardiac output was elevated at 30 min of CO hypoxia in all groups (p < 0.01) and in the severe CO group at 60 min (p < 0.01). Hindlimb blood flow remained unchanged during CO hypoxia in the intact groups. In the denervated group, hindlimb blood flow was greater (p < 0.05) than that in the intact groups throughout the experiment. A decrease in mean arterial pressure (p < 0.01) in all groups was associated with a fall in total resistance (p < 0.01). Hindlimb resistance remained unchanged during moderate CO hypoxia in the intact group but increased (p < 0.05) in the denervated group. In the severe CO group hindlimb resistance was decreased (p < 0.05) at 60 min. The results indicate that the increase in cardiac output during CO hypoxia was directed to nonmuscle areas of the body and that intact sympathetic innervation was required to achieve this redistribution.
Effect of upper airway carbon dioxide on ventilation and blood gases in the awake pony
Authors: Orr James A. , Fraser David B. , Shirer Hampton W. , Wagerle L. Craig , DeSoignie Roland C.
Published: April 2011

Carbon dioxide concentrations were increased during expiration in the upper one-half of the trachea, pharynx, and nasal sinuses to determine if elevation of upper airway CO2 would alter breathing or arterial blood gases in the awake pony. Carbon dioxide (100%) was injected into the midcervical trachea via a chronically implanted transcutaneous cannula during the first part of the animal's expiration. This maneuver elevated upper airway expiratory CO2 concentrations but prevented any exogenous CO2 from entering the lung and being absorbed into the arterial blood. Twelve experiments were performed on six ponies in which upper airway CO2 was elevated 2, 4, and 6% above the normal expired CO2 concentrations. Tidal volume increased in a dose dependent manner during upper airway CO2 exposure, but total ventilation was unchanged from base-line measurements made while the animal breathed room air. Arterial [Formula: see text] also increased during upper airway CO2 administration, reaching a mean value 6 Torr (1 Torr = 133.322 Pa) greater than the base-line values at the +6% CO2 exposure. We conclude that upper airway CO2 exposure alters breathing pattern slightly (increases tidal volume) and increases arterial [Formula: see text] in the awake pony.
Cardiovascular effects of atrial extracts in anesthetized rats
Authors: Ackermann Uwe , Irizawa Terumi G. , Milojevic Susan , Sonnenberg Harald
Published: April 2011

Tissue extracts derived from atria or ventricles of Sprague–Dawley rats were injected into Inactin-anesthetized assay rats. Compared with ventricular extracts, atrial extracts produced a 20 mmHg (1 mmHg = 133.322 Pa) fall in mean arterial blood pressure. This fall resulted from failure to increase cardiac output in compensation for peripheral vasodilation. Two factors were responsible: depression of heart rate (by 25 beats/min) and failure to increase cardiac performance. The time patterns and magnitudes of changes in cardiovascular parameters after cardiac extracts were not changed by prior atropinization. However, assay rats that were vagotomized showed no cardiac slowing after atrial extract and showed a significantly smaller decrease in mean arterial blood pressure than did sham-vagotomized or intact rats. Another group of assay rats was vagotomized as well as carotid-sinus-denervated before extract injection. In these rats the degree of hypotension caused by atrial extract was significantly greater than that observed after vagotomy alone and was not significantly different from that observed in rats with intact innervation. The results suggest that the hypotension that is caused by atrial extract, but not by ventricular extracts, results in part from the reflex effects of direct stimulation of chemosensitive cardiopulmonary receptors with vagal afferents and partly from the reflex effects of baroreceptor unloading. Ventricular extract had no hypotensive effect in any group of assay rats.
Seasonal changes in the endocrine responsiveness of the pituitary and testes of male sheep in relation to their patterns of gonadotropic hormone and testosterone secretion
Authors: Sanford L. M. , Howland B. E. , Palmer W. M.
Published: April 2011

Pituitary and testicular endocrine responses to exogenous gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH), respectively, were assessed for adult rams in an investigation of the regulation of seasonal changes in the patterns of episodic LH and testosterone secretion. Concurrent variations in testis size and in circulating levels of follicle stimulating hormone (FSH) and prolactin (PRL) were also examined. On 10 occasions throughout the year, serum hormone levels were assessed over 6- to 8-h periods during which time rams were left untreated (day 1) or were injected (iv) with single doses of either 10 μg synthetic GnRH (day 2) or 30 μg NIH-LH-S18 (day 3); blood samples were collected from the jugular vein at 10- or 20-min intervals. Testicular redevelopment during the summer, as indicated by increasing testis diameter measurements, was associated with increases in mean FSH level and was preceded by a springtime rise in mean PRL level; "spontaneously" occurring LH pulses and those produced in response to GnRH treatment were relatively large during this period. Increases in the magnitude of testosterone elevations in response to both endogenously and exogenously produced LH pulses occurred in August. Mean testosterone levels were elevated fourfold in the fall as a consequence of relatively frequent and small LH pulses stimulating a more responsive testis to produce more frequent and larger testosterone elevations; endogenous LH pulses, however, did not appear to stimulate the testes maximally at this time. Testicular regression occurred during the winter months and was characterized initially by decreases in testosterone levels without obvious changes in the pattern of pulsatile LH release and subsequently by a decrease in testicular responsiveness to relatively infrequent LH pulses which led to further decreases in testosterone levels and smaller testes. Results demonstrate that alterations in pituitary and testicular responsiveness to stimulatory hormones account in part for seasonal changes in the magnitude of LH and testosterone secretory pulses in adult rams.
Amitriptyline and imipramine inhibit the release of acetylcholine from parasympathetic nerve terminals in the rat iris
Authors: Richardson J. S. , Mattio T. G. , Giacobini E.
Published: April 2011

The electrically stimulated release of [3H]acetylcholine from the parasympathetic nerve terminals of the rat iris in vitro is increased in a dose-dependent manner by scopolamine but is decreased by the tricyclic antidepressants amitriptyline and imipramine. The increased release in the presence of scopolamine seems to be due to the blockade of a presynaptic muscarinic autoreceptor that, in the drug-free state, inhibits the release of acetylcholine. However, at drug concentrations that should have comparable antimuscarinic potency, the antidepressants inhibit the release of acetylcholine. This suggests that the anticholinergic side effects of the antidepressants may be due to the reduced release of acetylcholine from parasympathetic nerve terminals as well as a possible direct postsynaptic muscarinic receptor blocking action. Whatever the mechanism of this action, the antidepressants do not have the same effect as scopolamine at the presynaptic muscarinic autoreceptor in the rat iris.
Progress and problems in understanding the involvement of calcium in heart function
Authors: Dhalla N. S. , Singal P. K. , Panagia V. , Harrow J. A. C. , Anand-Srivastava M. B. , Beamish R. E.
Published: April 2011

In this article we have briefly reviewed the role of Ca2+ in the excitation contraction coupling in the myocardium and have indicated that cardiac contraction and relaxation are initiated upon raising and lowering the intracellular concentration of free Ca2+, respectively. Different mechanisms for the entry of Ca2+ through sarcolemma as well as release of Ca2+ from sarcoplasmic reticulum and possibly mitochondria have been outlined for initiating cardiac contraction. Relaxation of the cardiac muscle appears to be intimately dependent upon efflux of Ca2+ through sarcolemma as well as sequestration of Ca2+ by the intracellular storage sites, particularly sarcoplasmic reticulum and possibly mitochondria. The actions of some pharmacological and pathophysiological interventions have been explained on the basis of changes in subcellular Ca2+ movements in myocardium. Quinidine, which produced an initial positive inotropic action on rat heart was also found to increase sarcolemmal Ca2+-ATPase activity without any changes in the Na+–K+ ATPase. Other antiarrhythmic agents, procainamide and lidocaine, also increased sarcolemmal Ca2+-ATPase activity without affecting the Na+–K+ ATPase. On the other hand, both Ca2+-ATPase and Na+–K+ ATPase activities were increased in heart sarcolemma obtained from cardiomyopathic hamsters. In this model the increased Ca2+-ATPase activity may promote the occurrence of intracellular Ca2+ overload in the cardiac cell whereas the increased Na+–K+ ATPase activity may increase Ca2+ efflux through Na+–Ca2+ exchange systems as an adaptive mechanism. It has been suggested that some caution should be exercised while interpreting the data from in vitro experiments in terms of functional changes in the myocardium. Furthermore, it has been proposed that the pathophysiology and pharmacology of Ca2+ movements at different membrane sites be understood fully in normal and diseased myocardium in order to improve the therapy of heart disease.
Role of calcium in heart metabolism
Authors: Bihler I.
Published: April 2011

The role of calcium in modulating the activity of enzymes and transport pathways in heart muscle is briefly reviewed, with emphasis on its participation in the modulation of sarcolemmal glucose transport, which is normally the rate-limiting step in glucose utilization. Evidence for and against the "calcium hypothesis" of glucose transport regulation is discussed. Data from isolated myocardial preparations are presented to illustrate the dependence of glucose transport on Ca2+ and the role of this ion in coupling changes in cellular activity and metabolism to appropriate adjustments in the transport rate. It is shown that glucose transport is stimulated when cytosolic Ca2+ levels are raised, e.g., by activation of sarcolemmal Na+–Ca2+ exchange, by beta-adrenergic agents, by muscular contraction and inotropic interventions, and by intracellular Ca2+ release from the sarcoplasmic reticulum and the mitochondria. Stimulation of transport by insulin is also partially Ca2+ dependent. The main negative feedback on glucose transport is from the oxidation of fatty acids, ketone bodies, etc., and it is suggested that alterations in mitochondrial Ca2+ fluxes may be responsible.
Membrane potential of vascular smooth muscle and hypertension in spontaneously hypertensive rats
Authors: Cheung D. W.
Published: April 2011

The resting membrane potential of tail arteries from spontaneously hypertensive rats (SHRs) and Wistar-Kyoto controls (WKYs) was compared. At 4–5 weeks old, the blood pressure and resting membrane potential of the SHRs was not significantly different from the WKYs. The blood pressure of 8- to 10-week-old SHRs increased significantly to 183 mmHg (1 mmHg = 133.322 Pa) from 127 mmHg at 4 weeks, and the membrane potential decreased from 60 to 51 mV. At 15 weeks of age, the blood pressure of the SHRs was 193 mmHg and the membrane potential was 49 mV. In WKYs, there was no significant change in membrane potential with age. The decrease in membrane potential in the SHRs is due to a decrease in the ouabain-sensitive electrogenic pumping. Chronic treatment of the SHRs with captopril (100 mg∙kg−1∙day−1) prevented the increase in blood pressure and the decrease in membrane potential.