bluuebunny/crossref_metadata_2025 huggingface dataset:
The dead zone of thermoregulation in normal and paraplegie man
Authors: Tam Hak-Shing , Darling Robert C. , Cheh Huk-Yuk , Downey John A.
Published: April 2011

Independent heating and cooling of the core and skin were performed to a normal and a paraplegic subject. It was found that the core threshold temperature for vasoconstriction release was between that for shivering and sweating. After the onset of sweating, vasodilation of the forearm was observed to increase sharply. The core threshold temperature of sweating of the paraplegic was 0.7 °C higher than that of the normal at corresponding mean sentient skin temperatures. No sweating was observed in the spinal man without raising his core temperature. It appeared that the dead zone of thermoregulation is shifted up in the spinal patient and the possible reasons for this are discussed.
Regional distribution of ethanol in the rat brain
Authors: Sunahara G. I. , Kalant H. , Schofield M. , Grupp L.
Published: April 2011

The regional distribution of ethanol in selected areas of the rat brain was studied after single intravenous and intraperitoneal injections. Ethanol concentrations (measured by gas–liquid chromatography) in cortex, striatum, and hippocampus were compared with arterial and venous blood alcohol concentrations.As previously reported, equilibrium between tissue and arterial blood occurred within 3 min and followed simple diffusion kinetics. At shorter time intervals (1 min) after injection, regional ethanol concentrations differed, possibly because of regional blood flow and tissue mass. Equilibrium between tissue and venous blood required 10–15 min and coincided with the disappearance of the arterial–venous difference.These findings suggest that tissue ethanol concentrations cannot be determined from venous blood samples until brain arteriovenous equilibrium has occurred. They also support the argument that alcohol concentrations in tissue perfusates do not necessarily provide a reliable guide to those in the tissue.
Inhibition of passive anaphylaxis induced in the rat hind paw and peritoneal cavity by N-(2-oxo-3,5,7-cycloheptatrien-l-yl)-aminooxoacetic acid ethyl ester (AY-25,674)
Authors: Martel R. R. , Klicius J. , Pinski J.
Published: April 2011

Passive anaphylaxis induced in the rat hind paw and peritoneal cavity with rat serum containing immunoglobulin E antibody was inhibited by N-(2-oxo-3,5,7-cycloheptatrien-1-yl)-aminooxoacetic acid ethyl ester (AY-25,674). In contrast with disodium cromoglycate (DSCG), AY-25,674 was orally active. Otherwise, the activity profile of AY-25,674 was similar to that of DSCG. Peak activity occurred a short time after administration, large doses produced tachyphylaxis, and anaphylactic histamine release from mast cells was inhibited. AY-25,674 did not inhibit increased vascular permeability produced by nonreaginic antibody, compound 48/80, serotonin, or histamine. It is concluded that AY-25,674 produces its antiallergic effects by inhibiting mediator release from mast cells by a mechanism similar to that of DSCG.
Decreased pulmonary vascular responses in dogs with increased pulmonary blood flow
Authors: Tucker Alan , Reeves John T. , Jackson Don L. , Grover Robert F.
Published: April 2011

We wished to determine whether high pulmonary blood How alters the pulmonary vascular responses to the vasoconstrictors, hypoxia and prostaglandin F2α (PGF2α). Acute or chronic left pulmonary artery (PA) occlusion was performed in dogs in order to create high pulmonary blood How conditions. Right lung pulmonary vascular resistance (PVR) during normoxia was reduced by both acute and chronic left PA occlusion, suggesting passive vasodilatation. Increases in right lung PVR induced by hypoxia (10–15% O2) and PGF2α (0.8–4 μg kg−1min−1) were attenuated both in acute and chronic left PA occluded dogs. Since the reductions in responsiveness were similar with acute and chronic increases in blood flow, the attenuating effect of high blood How was not dependent upon morphologic changes in the vasculature. Pulmonary vascular responsiveness was probably reduced in these animals due to their dilated pulmonary vascular beds, consequent to the increased pulmonary blood How, thereby decreasing the effectiveness of smooth muscle contraction.
Evidence for enhanced Na transport in hypertension induced by DOCA in the rat
Authors: Friedman Sydney M. , Nakashima Miyoshi
Published: April 2011

Uninephrectomized rats were treated with DOCA-saline for 3 weeks. Active Na transport activity was assessed in the rat tail artery in three separate ways. In the first method, Na–K exchange was expressed in terms of steady-state values in normal and ouabain-blocked arteries. In the second method, the relation of free cell Na to [Na]0 was measured after equilibration in media in which [Na]0 varied from about 25 to 140 mM. In the third method, the relation of cell K to [K]0 was measured with glass electrodes during the reestablishment of normality following prolonged K depletion. All methods yielded evidence of enhanced net active transport activity in the incubated artery (zero intraluminal pressure) in steady state.
The uptake and efflux of α-aminoisobutyric acid by the smooth muscle of the guinea pig's taenia coli
Authors: Widdicombe J. H. , Paton D. M.
Published: April 2011

The uptake of α-aminoisobutyric acid (AIB) by guinea pig taenia coli was linear with time over a 5-h period. There was a saturable component with Km of 0.7 mM and a maximal value of 4.75 mmol/kg tissue per hour. A second nonsaturable component of uptake became important at high concentrations of AIB (> 5 mM). Preincubation in K+-free or Na+-free (high-K+) media greatly reduced uptake. The dependence of AIB uptake on outside [Na+] ([Na+]0) was approximately linear over the range 0–140 mM. With [Na+]0 equal to 25 mM the uptakes with various substitutes were in the order sucrose > Mg2+ > choline+ > Li+ > Cs+ > Rb+ = K+. Addition of ouabain or removal of K+ during efflux of AIB led to marked increases in the efflux rate, ouabain being the more effective treatment. Changes in tissue Na+ and K+ levels were found to be slightly greater with ouabain than with K+-free medium. Lanthanum (5 mM) prevented the uptake of Na+ seen in K+-free medium and also abolished the increase in the rate of loss of AIB. It also reduced the rise in tissue Na+ produced by ouabain; there was a corresponding reduction in the ouabain-induced increase in the rate of loss of AIB. It is concluded that both the influx and efflux of AIB in this tissue are Na+ dependent, and that the accumulation of AIB relies on the transmembrane Na+ gradient.
Number of nuclei in mammalian cardiac myocytes
Authors: Korecky B. , Sweet S. , Rakusan K.
Published: April 2011

The numbers of nuclei per cardiac muscle cell were determined in adult mammalian hearts after previous enzymatic isolation of individual myocytes. A high percentage of binucleation was observed in rat (78 ± 1.8%), rabbit (78 ± 0.8%), guinea pig (81 ± 1.6%), cat (76 ± 1.5%), dog (47 ± 2.4%,), and beef (45 ± 1.1%), while the human myocytes were found predominantly mononucleated (90%) and only 10 ± 2.2% of them were binucleated. These findings are in agreement with our data obtained after serial sectioning of the myocardium of the above species and subsequent reconstruction of individual myocytes. We also found that in fetal and neonatal rat the cardiac myocytes are predominantly mononucleated (95% and 84%, respectively), that the binucleation develops during the early postnatal period, and that adult values are reached by 12–14 days of age. When the body growth and consequently also the heart growth were either accelerated or slowed down by nutritional intervention during the above period, the rate of appearance of binucleation correlated with the organ size rather than with the age of the rat. Early postnatal increase in binucleation was also observed in rabbit, cat, and dog during normal growth. The regional distribution of the above phenomenon was found to be uniform throughout both ventricles.
Evidence for two adenine derivative receptors in rat ileum which are not involved in the nonadrenergic, noncholinergic response
Authors: Bartlett V. , Stewart R. R. , Nakatsu K.
Published: April 2011

The receptors mediating inhibition of the rat ileum by adenosine and adenine nucleotides were studied. ATP and ADP were more potent than AMP or adenosine. Theophylline antagonized the effects of adenosine and AMP but not those of ATP or ADP. Preparations desensitized to ATP or ADP were still inhibited by adenosine and vice versa. The nonadrenergic, noncholinergic inhibition produced by field stimulation or nicotine was not attenuated by the presence of theophylline or desensitization to ATP. These data indicate that more than one adenine derivative receptor is present in rat ileum and that ATP and adenosine are unlikely candidates for the unknown transmitter.
An opiate receptor on frog sciatic nerve axons
Authors: Hunter E. G. , Frank G. B.
Published: April 2011

The effect of meperidine (3 × 10−4 M) on the action potential of frog sciatic nerve was examined by means of the double sucrose gap technique. Meperidine decreased the amplitude, maximum rate of depolarization, and maximum rate of repolarization of the action potential but had no effect on the resting potential. This depression in amplitude and maximum rate of rise was partially blocked by naloxone (1 × 10−8 M) while the maximum rate of depolarization was further depressed. The data suggest that the effect of meperidine is due to two mechanisms, a nonspecific local anaesthetic like effect and an opiate receptor mediated effect.
Noradrenaline inhibition of transmitter efflux in a renal artery preparation and the presynaptic receptor theory
Authors: Chan Chi-Chung , Kalsner Stanley
Published: April 2011

The effect of noradrenaline on the stimulation-induced efflux of tritium in cattle renal arteries preincubated with [3H]noradrenaline was determined. Preparations were stimulated transmurally, with 300 shocks over a range of frequencies (1–15 Hz) in the presence and absence of noradrenaline (3 × 10−6 M). The agonist inhibited the efflux most at 1 Hz but the extent of the inhibition did not vary with frequency between 2, 5, and 15 Hz. It is concluded that a negative feedback system, modulating neurotransmitter release, and increasingly activated by endogenously released noradrenaline as the frequency of stimulation rises, cannot account for the pattern of efflux inhibition induced by exogenous noradrenaline.
Calcium ion stimulated endogenous protein kinase catalyzed phosphorylation of peripheral nerve myelin proteins
Authors: Petrali Elena H. , Sulakhe Prakash V.
Published: April 2011

Myelin isolated from the rat peripheral nervous system (sciatic nerve and cauda equina) contained Mg2+-dependent protein kinase that phosphorylated myelin polypeptides. Ca2+, in micromolar concentrations, markedly stimulated phosphorylation (half-maximal stimulation at 5 μM (free) Ca2+) but at higher concentrations (> 100 μM Ca2+) it caused inhibition. In the presence of Triton X-100, phosphorylation (±Ca2+) of myelin was increased and Ca2+ caused up to a 10-fold increase in phosphorylation. Among the myelin polypeptides, P0 (Mr, 28 000), a major glycoprotein, accounted for nearly 60% of the total phosphate incorporated into the myelin and Ca2+ markedly promoted phosphorylation of P0. Phosphorylation of other myelin polypeptides, P2 (Mr, 16 000), Y (Mr, 26 000), and P1 (Mr, 20 000), and the Ca2+-stimulatory effect on phosphorylation of these were also evident. Cyclic AMP (or other cyclic nucleotides) failed to show any significant stimulatory effect on myelin phosphorylation.
Contractile failure and recovery in rat hearts perfused with Na+- or K+-free medium
Authors: Singal P. K. , Yates J. C. , Dhillon K. S. , Dhalla N. S.
Published: April 2011

Ca2+ or K+ concentrations during Na+-free perfusion and Ca2+ or Na+ concentrations during K+-free perfusion were varied and the effects on the contractile force were recorded during failure as well as recovery of the hearts. The initial positive inotropic effect of zero Na+ was directly related to the Ca2+ or K+ concentration of the medium. The time of failure was not affected by changes in Ca2+ concentrations of the Na+-free medium whereas lowering of K+ concentration prolonged the time of failure. The initial negative inotropic effect of perfusion with zero K+ was increased by low Ca2+ and was changed to a positive effect by high Ca2+; the time of failure was inversely related to the Ca2+ concentration. Lowering of Na+ in zero K+ medium caused fibrillation of the heart.The recovery upon reperfusion with control medium of Na+-deprived hearts was improved by a reduction in Ca2+ concentration during Na+-free perfusion and was adversely affected by increased Ca2+. Increases or decreases in K+ during Na+-free perfusion reduced recovery. The length of the fibrillation period was affected in a characteristic manner by changes in Ca2+ or K+ concentrations. The recovery of the K+-deprived hearts was also influenced by changes in Ca2+ or Na+ concentrations during K+-free perfusion. In addition to altering the electrical properties of the myocardium, the early effect of Na+ or K+ lack appears to be on the Ca2+ movements across the sarcolemma and this is followed by the intracellular Ca2+ overload. The study emphasizes the importance of a proper balance between the Na+, K+, and Ca2+ concentrations for normal functioning of the heart.
Metabolism of the perfused rabbit heart. IV. Effects of β-adrenergic blockade on enzyme release and late energy stores during postanoxic reoxygenation
Authors: Chiong Miguel A. , Stefaniszyn Henry
Published: April 2011

The effects of 80 μM dl-propranolol on left ventricular (LV) performance, energy stores, and creatine kinase (CK) release were studied in a modified Langendorff rabbit heart preparation during 75 min of aerobic perfusion and postanoxic reoxygenation.The data showed that this concentration of propranolol, which blocked the effects of β-adrenergic stimulation without affecting LV performance, coronary sinus flow (CSF), or oxygen consumption [Formula: see text], was associated with greater stores of glycogen and adenine nucleotides at the end of aerobic perfusion. Similar effects were observed during postanoxic reoxygenation, when recoveries of left ventricular systolic pressure, heart rate, heart rate - left ventricular systolic pressure product, CSF, and [Formula: see text] remained unchanged during propranolol administration, but myocardial concentrations of glycogen, creatine phosphate, and ATP were greater and the ATP:AMP ratio and the energy charge were higher than in untreated hearts. In addition, the rate of CK loss was lower in the blocked postanoxic hearts than in the unblocked group. These results indicate that propranolol had a beneficial effect on cardiac metabolism during postanoxic recovery tending to normalize energy stores and to reduce enzyme loss during reoxygenation of perfused rabbit hearts without affecting mechanical performance, coronary flow, or O2 metabolism.
Comparative biochemical profiles in blood and urine of two strains of mink and changes associated with the incidence of wet belly disease
Authors: Sorfleet J. L. , Chavez E. R.
Published: April 2011

The blood and urine biochemical profiles of two color strains of mink, Demi-Buff and Pastel, were studied. Changes associated with the incidence of wet belly disease in some of them were determined by comparison with unaffected animals. Chloride and potassium were the only blood parameters significantly different between these two strains of mink. In blood, [Formula: see text] was the only significant difference detected between wet belly affected and unaffected mink. Pastel mink excreted significantly more potassium and nitrogen in the daily urine excretion than did the Demi-Buff strain. The most significant findings were observed in the urine of mink affected with wet belly disease when compared with unaffected animals. Twenty-four hour urine excretion volume was significantly reduced in mink with wet belly disease. Chloride, ammonia, and net acid were significantly higher than normal in the urine of mink with wet belly disease.
Measurement of total ammonia levels in plasma, whole blood, and cerebrospinal fluid of dogs using an ion-specific electrode
Authors: Davidson J. S. D. , Jennings D. B.
Published: April 2011

[NH3] (dissolved NH3 plus NH4+) was measured in cerebrospinal fluid (CSF) and blood of awake and anesthetized dogs using an ion-specific electrode. When oxalate was used as an anticoagulant, plasma [NH3] was increased by 46% in comparison with plasma [NH3] when the anticoagulant was "NH3-free" heparin. As whole blood [NH3] was the same using either anticoagulant, the choice of anticoagulant influenced distribution of NH3 between plasma and red blood cells. In awake animals venous [NH3] was the same as arterial [NH3]; however, following anesthesia plasma [NH3] increased significantly and there was a tendency for venous [NH3] to exceed arterial [NH3]. In some dogs, anesthesia resulted in marked changes in arterial and (or) venous plasma and whole blood [NH3]. Examination of the red blood cell:plasma ratio for [NH3] indicated that ammonia may not be distributed passively between the two compartments. Similarly, calculations of ammonia distribution between CSF and plasma indicated that ammonia is unlikely to be distributed by passive forces between CSF and plasma.
Tubular reabsorption of α-aminoisobutyric acid in the pre-steady-state. Evidence for a cell-to-lumen flux
Authors: McInnes Roderick R. , Mohyuddin Fazl , Scriver Charles R.
Published: April 2011

We investigated time-dependent and concentration-dependent renal handling of α-aminoisobutyric acid (AIB) in the rat during seven consecutive 30-min clearance periods after onset of AIB infusion. Following low-level rapid venous infusion of AIB (9.75 μmol/kg in 30 s), plasma [AIB] fell exponentially in the initial three periods and in linear fashion (−0.00158 μM/min) thereafter. Although filtered AIB fell in proportion to plasma [AIB] during the early clearance periods (5–125 min), fractional excretion of AIB (FEAIB) rose (Δ FEAIB = +0.077 ± 0.010, mean ± SD) and stabilized only in later clearance periods (125–215 min). Saturable intrarenal binding does not explain rising FEAIB with falling plasma [AIB] because sequential infusions of AIB, 120 min apart, also elicited the phenomenon after each infusion. During continuous infusions of AIB, time dependence of FEAIB was also observed, in the early interval (5–95 min), after onset of AIB infusion at various concentrations of plasma [AIB] below 3 mM approximately. Measurement of concentration-dependent net tubular reabsorption of AIB in the fourth through seventh clearance periods (near the steady state) revealed progressive saturation over the whole range of plasma [AIB] (0–12 mM), yet with a collapse of net reabsorption in the plasma [AIB] range 2–4 mM. Measurements of renal tissue AIB in these experiments revealed that cellular AIB is of sufficient magnitude and bears such a relationship to plasma AIB and FEAIB that it could contribute to an observable cell-to-lumen movement of amino acid in the "pre-steady-state" situation and could account for the rise in FEAIB following AIB infusion and the collapse in tubular reabsorption of AIB at 2–4 mM plasma [AIB].
Effect of pH on muscle fatigue in isolated frog sartorius muscle
Authors: Stevens E. Don
Published: April 2011

Isolated frog sartorius muscle was incubated for 3 h in Ringer solution (5 mM phosphate buffer) at pH 7 or pH 8. Each muscle was stimulated supramaximally at 2 per second continuously. Muscles at pH 7 fatigued more quickly than those at pH 8. Muscles at pH 8 released acid whereas those at pH 7 did not.
Specific binding of 2-[3H]chloroadenosine to rat brain cortical membranes
Authors: Wu P. H. , Phillisk J. W. , Balls K. , Rinaldi B.
Published: April 2011

2-[3H]Chloroadenosine was used as a ligand to investigate the presence of adenosine receptors on rat brain cortical membranes. The binding studies reveal the presence of a single binding site which has an apparent dissociation constant (KD) of 23.5 nM and a maximal binding capacity (Bmax) of 476 fmol/mg protein. This binding can be inhibited by adenosine, adenine, nicotinamide adenine dinucleotide phosphate, inosine, theophylline, and isobutylmethylxanthine. These findings strongly support the suggestion that there is an adenosine receptor on brain cell membranes.
Histamine receptors and cyclic AMP
Authors: McNeill John H.
Published: April 2011

The identification and characterization of histamine receptors in the organ systems of various species has been made possible in recent years by the introduction of relatively selective agonists and antagonists of H1 and H2 receptors. H2 receptors have now been clearly demonstrated in gastric mucosa, heart, rat uterus, brain, and adipose tissue. Less well-defined H2 receptor systems have also been described in the vasculature, bronchioles, and other smooth muscles as well as in the thyroid gland and lymphocytes. In tissues where it has been examined a close correlation between H2 receptors and the adenylate cyclase – cyclic AMP system has been found. With the exception of the central nervous system stimulation of H1 receptors does not seem to be involved with cyclic AMP. In the case of the brain the H1 receptor stimulation of adenylate cyclase can be differentiated from H2 receptor stimulation of the enzyme by the use of blocking agents and by the fact that the H1 receptor response is enhanced in the presence of adenosine. Studies of the involvement of histamine with the adenylate cyclase – cyclic AMP system have been concentrated on such tissues as gastric mucosa, heart, rat uterus, brain, and adipose tissue. The present review will concentrate on the literature concerning those tissues.
The effect of indomethacin and adenosine 5′-triphosphate on the excitatory innervation of the rat urinary bladder
Authors: Choo L. K. , Mitchelson F.
Published: April 2011

Adenosine 5′-triphosphate (ATP) (20–400 μM) contracted 48% of isolated rat urinary bladder preparations but induced no response in the remainder. The response to ATP never exceeded 25% of the response to electrical stimulation in the presence of indomethacin (50 μM) plus hyoscine (25 μM) and usually developed more slowly than that to electrical stimulation. Autoinhibition could be produced to ATP by incubating the tissue with ATP (200 μM) for 20 min. Incubation of the tissue with ATP (200 μM) for 60 min in the presence of indomethacin (50 μM) and either hyoscine (25 μM) or hemicholinium-3 (500 μM) reduced but failed to abolish responses to electrical stimulation. Responses to acetylcholine were not affected by ATP (200 μM) in the presence of indomethacin and the output of acetylcholine induced by neuronal stimulation at 10 Hz was not inhibited by ATP (200 μM) or by indomethacin (50 μM). The results suggest a possible modulatory role for ATP in the excitatory innervation of the rat urinary bladder.
Action de l'acide cholique et de l'acide chénodesoxycholique sur la sécrétion biliaire de la souris. Effet de l'addition du β-sitostérol
Authors: Marteau Ch. , Reynier M. O. , Crotte C. , Mule A. , Mathieu S. , Gerolami A.
Published: April 2011

After this time, the cholesterol intestinal absorption and the biliary secretion of lipids were measured. The biliary secretion of cholesterol, the total hepatic cholesterol (23 mg/g liver dry weight), and the intestinal absorption of cholesterol (90% administered dose) were higher in mice fed with cholic acid than in mice fed with chenodeoxycholic acid (hepatic cholesterol, 9.6 mg/g liver dry weight; absorption, 65% administered dose).The addition of β-sitosterol to the diet supplemented with cholic acid decreased the cholesterol intestinal absorption and the biliary secretion of cholesterol so that both became similar to that obtained with chenodeoxycholic acid.These results indicate that in mice, as in man, cholic acid elicits a higher cholesterol biliary secretion than chenodeoxycholic acid. In this experimental model, the distinct effect on the biliary cholesterol of these two bile salts is due to their specific effects on the intestinal absorption of cholesterol.
Renal tubular transport in phosphate depletion: a micropuncture study
Authors: Wong Norman L. M. , Quamme Gary A. , O'Callaghan Thomas J. , Sutton Roger A. L. , Dirks John H.
Published: April 2011

The acute effects of intravenous infusions of phosphate and parathyroid hormone (PTH) upon the renal tubular handling of sodium, potassium, calcium, magnesium, and phosphate were examined in phosphate-depleted dogs using recollection micropuncture techniques. Hypercalciuria in phosphate depletion results from an impairment of calcium reabsorption between proximal and distal sampling sites, which can be partially corrected by the acute administration of PTH or by phosphate infusion. Magnesium reabsorption was normal in phosphate-depleted dogs but increased in parallel with calcium in the distal tubule following PTH and phosphate infusion. Phosphate was avidly reabsorbed in the phosphate-depleted dog so that excretion was very low even during the infusion of PTH or of neutral phosphate. Only with the infusion of both PTH and phosphate was a normal phosphaturic response observed.
Ristocetin–Willebrand factor activity in dog plasma
Authors: Johnstone I. B. , Lotz F.
Published: April 2011

A sensitive and reproducible method for the quantitation of ristocetin–Willebrand factor activity in canine plasma is described. This assay measures the initial velocity of aggregation of suspensions of canine washed platelets in the presence of ristocetin and ristocetin–Willebrand factor. The washed platelets are stable for 4 h and when prepared from the same donor vary little in their day-to-day response to ristocetin.The calculated mean plasma ristocetin–Willebrand factor activity in 37 normal dogs using this method is 98 ± 26% (mean ± SD). Ristocetin–Willebrand activity is 106 ± 25% in dogs with severe hemophilia A and 45 ± 13% in dogs with moderate forms of von Willebrand's disease.
Effects of tonin on the response to norepinephrine by the aortic strip of the hypertensive rat
Authors: Garcia R. , Schiffrin E. L. , Thibault G. , Boucher R. , Genest J.
Published: April 2011

The response to norepinephrine (NE) of arterial smooth muscle from two types of experimental hypertensive rats was investigated. Aortic strips from one-kidney, one-clip hypertensive animals were less responsive to NE than those from their normotensive controls but strips from two-kidney, one-clip hypertensive animals showed no difference from their corresponding controls. The contractility in response to NE was the same in all groups. These results suggest that the mechanisms responsible for the lesser reactivity in the one-kidney hypertensive group are not a consequence of elevated blood pressure itself but may be related to changes in the intrinsic sensitivity of aortic smooth muscle.Tonin potentiated the contraction induced by NE in aortic strips from hypertensive and normotensive rats. This effect was more pronounced in the one-kidney, one-clip hypertensive animals, so that although the aortic smooth muscle from these animals is less reactive to NE, the decreased reactivity can be more than compensated by the presence of tonin. The mechanism of potentiation is not yet clear but the fact that Saralasin did not inhibit it suggests that angiotensin Il is not generated in situ.
Detection from rat pituitary of β-lipotropin and materials containing opiatelike activity by combined enzymatic radioreceptor assay
Authors: Chan J. S. D. , Seidah N. G. , Ikeda M. , Gutkowska J. , Boucher R. , Genest J. , Chretien M.
Published: April 2011

Tonin, a proteolytic enzyme isolated from rat submaxillary gland, was allowed to react upon ovine β-lipotropin (β-LPH) at 37 °C at a variety of pH values and for different lengths of time. Opiatelike activity generated by the reaction was assessed using a radioreceptor assay for β-endorphin with rat brain homogenate, [3H]naloxone, and β-endorphin as receptors, tracer, and hormone standard, respectively. Cleavage of β-LPH with tonin produced a 10-fold increase in opiatelike activity as compared with β-LPH alone. Digestion of β-LPH with other enzymes such as renin, eathepsin D, trypsin, and chymotrypsin produced much less opiatelike activity. β-Endorphin and methionine-enkephalin were not cleaved by tonin. Using this new assay, we were able to detect β-LPH and materials containing opiatelike activity from rat pituitary extracts after gel chromatography. It is more specific and more sensitive than trypsin digest.
Transducer properties of atrial receptors in the dog after 60 min of increased atrial pressure
Authors: Kappagoda C. T. , Padsha M.
Published: April 2011

This investigation was undertaken to examine the effect of a period of increased atrial pressure lasting 60 min on the ability of atrial receptors to transduce changes in atrial pressure. The experiments were performed on dogs anesthetized with pentobarbitone. Action potentials were recorded from branches of the cervical vagi and the atrial pressure was increased by distending a balloon in the lumen of the left atrium. Twelve receptors were examined in 14 dogs. For each receptor, stimulus–response curves relating the action potentials generated (number per cardiac cycle) to the mean left atrial pressure (centimetres of H2O) were obtained under three experimental conditions: (a) during an initial control period, (b) after 60 min of increased atrial pressure (i.e. 10–12 cm H2O), and (c) 60 min after restoration of the atrial pressure to its control value. It was found that in all 12 units the ability of the receptors to transduce changes in atrial pressure was impaired after 60 min of increased atrial pressure, i.e., the number of action potentials generated by a receptor for the same atrial pressure was smaller than that in the control period. This effect was partially restored in the 12 units 60 min after restoration of the atrial pressures to their respective control values.In four units the stimulus–response curves were repeated 60 min after obtaining the initial control response. It was found that there was no significant difference in each pair of curves. It is concluded that relatively short periods of increased atrial pressure impair transducer properties of the atrial receptors.
Thermoregulatory responses of tailed and tailless rats to isoproterenol
Authors: Spiers Donald E. , Barney Christopher C. , Fregly Melvin J.
Published: April 2011

Colonic temperatures were measured in tailed and tailless rats at an ambient temperature (Ta) of 26 °C prior to and following administration of isoproterenol, a β-adrenergic agonist, at doses of 0, 12.5, 25.0, 50.0, and 100.0 μg∙kg−1. There was no significant difference between the colonic temperatures of tailed and tailless rats before drug injection. However, mean colonic temperature of tailless rats increased to a maximal level approximately 0.3° higher than that of tailed rats after injection of 25.0, 50.0, and 100.0 μg isoproterenol per kilogram. The duration of the hyperthermic response was 50–60 min longer in tailless than tailed rats after administration of 50 and 100 μg isoproterenol per kilogram. The rate of oxygen consumption (heat production) increased by 4.5 mL∙min−1∙kg−0.75 in both tailed and tailless rats after administration of 50 μg isoproterenol per kilogram, the only dose tested. Mean colonic temperature of tailless rats was significantly higher, by 0.2–0.5°. than that of tailed rats during the initial 60 min of exposure to Ta 36 °C and during the first 40 min following removal from Ta 40 °C to Ta 28 °C. These results suggest that the tail of the rat is required for short-term maintenance of colonic temperature during both external and internal heat stresses.
Human interferon for clinical trials: removal of pyrogen by a simple two-step procedure
Authors: Borg H. , Lundgren E. , Hollenberg M. D. , Veale W. L. , Tan Y. H. , McPherson A.
Published: April 2011

Commonly used preparations of human interferon are pyrogenic when used in humans for clinical trials. We describe a simple two-step procedure for the purification of human fibroblast interferon, employing Blue Sepharose chromatography and high-speed centrifugation. Such preparations are devoid of pyrogenic activity in a rabbit test system and are much more suitable for use in human clinical trials than previously used preparations.
Synaptic transmission in suprasylvian visual cortex is reduced by excitatory amino acid antagonists
Authors: Hicks T. P. , Guedes R. C. A.
Published: April 2011

The activities of cortical neurones lying in the Clare – Bishop area of the suprasylvian visual region in anaesthetized cats were monitored during the application of cholinergic and amino acid agonists and antagonists, as well as during sequences of light and electrical stimulation. Of those Clare – Bishop cells which could be activated at short latencies by electrical stimuli applied to the contralaterial, homologous cortical zone, D-α-aminoadipate and 2-amino-5-phosphonovalerate antagonized neuronal responses elicited by electrically evoked synaptic activation and by the presentation of light stimuli. Acetylcholine as well as the excitatory amino acids increased the firing of many of these neurones; however only the amino acid antagonists blocked the commissurally evoked excitations although both types of antagonist reduced the magnitudes of the visually evoked responses. It therefore appears as though the same synaptic transmitter is utilized by cortical commissural afferents as is employed by the cortical ipsilateral projection to the Clare – Bishop area, and furthermore this transmitter is likely to be an excitatory amino acid.
Effects of L-bromotetramisole on phosphate transport by the proximal renal tubule: failure to demonstrate a direct involvement of alkaline phosphatase
Authors: Brunette Michele G. , Dennis Vincent W.
Published: April 2011

Several recent studies have suggested that the alkaline phosphatase situated in the brush border membrane of the proximal convoluted tubule is positively related to inorganic phosphate reabsorption through this segment of the nephron. We examined this hypothesis by studying the influence of an inhibitor of alkaline phosphatase, L-bromotetramisole, upon phosphate transport through the isolated rabbit tubule, phosphate transport through brush border membrane vesicles of rats, and phosphate efflux from these vesicles. Results were compared with those obtained with D-bromotetramisole which is inactive on alkaline phosphatase.The microperfusion studies on isolated tubules did not show any significant influence of L-bromotetramisole on phosphate transport which slightly increased by 0.22 ± 0.78 pmol ∙ mm−1 ∙ min−1 (NS).The experiments performed on brush border membrane vesicles indicated that at pH 7.5, both L- and D-bromotetramisole at a concentration of 0.1 mM slightly but significantly increased phosphate input from 1800 ± 149 to 1999 ± 157 and 1982 ± 168 pmol/mg protein per 30-s incubation (P < 0.01 and P < 0.005, respectively). At pH 8.5, the same tendency was observed but was significant with the D isomer only. Finally, the effect of an increasing phosphate transport was accentuated when both isomers were tested at 1.0-mM concentration. Phosphate efflux from brush border membrane vesicles was not influenced by L- or D-bromotetramisole at 0.1 mM. At 1.0 mM, however, both isomers accelerated this release.These results do not support the hypothesis of a direct action of alkaline phosphatase upon phosphate transport through the entire proximal convoluted tubule, nor upon input or output of this electrolyte through the brush border membrane vesicles. The two forms of bromotetramisole have variable effects upon phosphate transport which are unrelated to the alkaline phosphatase activity.
Changes of gap junctions in myometrium of guinea pig at parturition and abortion
Authors: Garfield R. E. , Daniel E. E. , Dukes M. , Fitzgerald J. D.
Published: April 2011

Myometrial tissues from guinea pigs were quantitatively examined for gap junctions in electron micrographs. Small numbers of gap junctions were present between smooth muscle cells in myometria of pregnant guinea pigs at days 50 and 65 of gestation. The junctions increased in number and size at parturition on day 69 and decreased again to control levels 24 h after parturition. A similar increase in junctions occurred when abortion was induced by 16,16-dimethylprostaglandin E2 (PGE2) on day 65. There were no consistent or significant differences in numbers of gap junctions from myometrium taken over sites of placental attachment and from other sites. These results together with previous studies suggest that an increase in myometrial gap junction area is associated with and may be essential for parturition in guinea pigs, but the control of their development may differ from that in other mammals.
Effects of antihypertensive clonidine congeners on alpha-adrenergic receptors
Authors: Titeler Milt , Seeman Philip
Published: April 2011

Evidence in the literature suggests that the antihypertensive effects of clonidine stem from its action on alpha-2 adrenergic receptors. In order to examine this possibility we tested the effects of 13 congeners of clonidine on the binding of [3H]WB-4101 and [3H]clonidine to calf frontal cortex homogenates; [3H]WB-4101 served as a label for alpha-1 receptors while [3H]clonidine served to label alpha-2 adrenergic receptors. All the substituted imidazolines were two to three orders more potent in inhibiting the binding of [3H]clonidine than they were against [3H]WB-4101. There was a strong correlation between the antihypertensive doses of these congeners and their concentrations required to inhibit the binding of [3H]clonidine. The results are compatible with the concept that the antihypertensive action of clonidine is more likely due to interactions with alpha-2 adrenergic receptors than with alpha-1 receptors.
Effects of estradiol on intact and denervated striatal dopamine receptors and on dopamine levels: a biochemical and behavioral study
Authors: Paolo T. Di , Bédard P. J. , Dupont A. , Poyet P. , Labrie F.
Published: April 2011

The present study describes the effect of chronic estrogen treatment on striatal dopamine levels and dopamine receptors, as well as on apomorphine-induced circling, a behavioral model reflecting dopaminergic activity in the rat striatum. Although estradiol itself does not show any affinity for the striatal dopamine receptor, its administration for 2 weeks in adult ovariectomized rats leads to a small increase of [3H]spiroperidol, [3H]haloperidol, and [3H]apomorphine binding in the striatum; this increase is associated with a greater number of binding sites. In order to dissociate possible pre- and post-synaptic effects of estrogens, these studies were next performed in animals bearing an unilateral 6-hydroxydopamine lesion of the substantia nigra. The apomorphine-induced circling behavior of rats bearing such a lesion was not affected by estrogen treatment. Estradiol treatment induced an increase of [3H]spiroperidol binding in both the intact and lesioned striatum, thus suggesting an estrogenic effect on a population of postsynaptic receptors. Chronic estradiol treatment reduced the concentration of dopamine in the striatum while the turnover of this amine measured using α-methyl-p-tyrosine remained unchanged. The present results show that estradiol exerts effects at the striatal level on both dopamine metabolism and receptor levels.
The antiarrhythmic action of encainide versus ventricular arrhythmias in the conscious dog following coronary artery ligation
Authors: Byrne Jeffrey E. , Gomoll Allen W.
Published: April 2011

Encainide (MJ 9067) was given intravenously at 1, 2, or 5 mg/kg and orally at 1, 2.5, 5, or 10 mg/kg to conscious dogs 18–23 h after two-stage ligation of the left anterior descending coronary artery. Heart rate and ventricular ectopic rate were lowered in a dose-related manner by 40–70 and 55–158 beats/min, respectively, following drug administration. Ventricular arrhythmia was frequently abolished with doses of 2 mg/kg and above. The onset of antiarrhythmic activity was 1–2 min after intravenous injection and 15–30 min after oral ingestion. The duration of effect was 6–7 h or longer following either route of drug administration. Emesis occurred in 1 of 10 and 1 of 6 dogs, respectively, at the 2 and 5 mg/kg intravenous dose levels. Brief ataxia was also observed in one dog given the latter dose.
Saliva progesterone throughout the menstrual cycle and late pregnancy
Authors: Connor M. L. , Sanford L. M. , Howland B. E.
Published: April 2011

Whole saliva was collected daily by four women during one menstrual cycle and twice weekly by three women during their third trimester of pregnancy. Follicular-phase saliva progesterone concentrations, as measured by radioimmunoassay, generally remained below 50 pg/mL. However, progesterone rose to a peak of 400 ± 107 pg/mL (mean ± SE) between days 17 and 25, after which it declined to 143 ± 67 pg/mL by one day prior to menses. The third trimester of pregnancy was characterized by steadily increasing concentrations of saliva progesterone until 1–3 weeks prior to parturition; concentrations following parturition were similar to those of the follicular phase.
Relationship between plasma corticosterone and adrenal epinephrine after diazepam treatment in rats
Authors: Chabot Guy , Brissette Yves , Gascon André L.
Published: April 2011

Following recent observations that diazepam treatment increases adrenal epinephrine in rats, we were interested in studying the possible mechanisms of this action of diazepam on rat adrenal glands. All diazepam treatments studied (1–25 mg∙kg−1∙day−1 for 10 days) led to an increase in adrenal epinephrine following a linear dose–effect relationship. Since epinephrine synthesis is under neuronal and humoral controls, we investigated their respective importance in the effect of diazepam on the adrenal gland. The denervation of the adrenal gland did not prevent the increase in adrenal epinephrine by diazepam treatment. On the other hand, diazepam treatment was shown to cause an increase in plasma corticosterone in parallel with an increase in adrenal epinephrine. Administration of dexamethasone (a synthetic corticoid) and hypophysectomy prevented the increase in adrenal epinephrine and plasma corticosterone resulting from diazepam treatment. We thus conclude that the increase in adrenal epinephrine seen after diazepam treatment is parallel to the increase in plasma corticosterone. Moreover, since the action of diazepam on adrenal epinephrine is prevented by dexamethasone or hypophysectomy, we hypothesize that diazepam is acting on the adrenal cortex via the release of adrenocorticotropic hormone (ACTH). ACTH and corticosterone would be responsible for the increased activity of epinephrine-synthesizing enzymes in adrenal medulla.
Effect of somatostatin on renal water handling in the dog
Authors: Mountokalakis Theodore , Levy Mortimer
Published: April 2011

When somatostatin was infused into the left renal artery of anaesthetized, hydropenic dogs in doses ranging from 1 to 10 μg/min, it produced an increased flow of a more dilute urine from the ipsilateral kidney. Similar infusions in dogs undergoing a maximal water diuresis had no effect. If aqueous antidiuretic hormone (ADH) was administered intravenously into water-loaded dogs prior to the intraarterial infusion of somatostatin, this latter peptide was able to produce an augmented flow of a more dilute urine from the ipsilateral kidney. If the left kidney was made to excrete a concentrated urine in the face of maximal water loading by restricting arterial perfusion, then the infusion of somatostatin had no effect on urinary dilution, though this peptide could increase water excretion in hydropenic dogs when the left kidney was similarly restricted as to arterial inflow. In dogs undergoing a water diuresis that were given cyclic AMP (4 mg/min) into the left renal artery, a decrease in ipsilateral water excretion was observed. The subsequent infusion of somatostatin produced no urinary dilution. We conclude that somatostatin increases renal water excretion by antagonizing the ADH effect on the renal tubule, and that this event probably occurs at a pre-cAMP site within the cell.
Epicardial coronary venous pressures: autonomic responses
Authors: Klassen G. A. , Armour J. A.
Published: April 2011

Intramyocardial, ventricular, aortic, and central and peripheral coronary artery as well as peripheral and central coronary venous pressures were measured simultaneously in dog hearts. A gradient of coronary vascular pressures was detected and quantitated. Stellate stimulation increased all pressures. Isoproterenol induced outflow tract obstructions so that aortic and central coronary artery pressures were unchanged while the other pressures increased. Vagal stimulation dissociated the intramyocardial venous pressure relationship in as much as arterial pressures decreased while epicardial coronary venous pressure was increased. These data suggest that coronary venous pressure in response to sympathetic stimulation increases as intramyocardial pressure increases. However, vagal stimulation permits a dissociation of these effects suggesting that coronary venous pressure regulation is complex.
Positive feedback regulation of noradrenaline release from sympathetic nerves: a questionable hypothesis
Authors: Kalsner Stanley
Published: April 2011

The effects of known agonists and of an antagonist on the stimulation-induced efflux of [3H]noradrenaline from left atria of guinea pigs was assessed. This was done to evaluate the hypothesis of presynaptic beta receptors mediating a positive feedback system. Isoproterenol (1.2 × 10−8 M) enhanced the efflux of tritium with 50 pulses at all four test frequencies and did so to a similar extent at three of them. Exogenous noradrenaline (1.8 × 10−6 M) inhibited efflux and isoproterenol was ineffective as an enhancer of efflux in its presence. Propranolol (1 × 10−7 M) did not reliably increase the inhibitory effect of added noradrenaline on stimulation-induced efflux nor did the antagonist by itself under a variety of test conditions decrease the stimulation-induced efflux of tritium. It is concluded that the synaptic quantities of transmitter do not determine the magnitudes of the effects of exogenous agents on tritium efflux and that positive feedback, for both theoretical and empirical considerations, does not function during neurosecretion
Evidence for mobilization of intracellular calcium during the contractile response of the rat aorta to U44069
Authors: Heaslip Richard J. , Rahwan Ralf G.
Published: April 2011

The aim of the present investigation was to elucidate the pharmacological mechanism by which U44069, a stable PGH2 analogue, contracts the rat aorta. The results obtained demonstrate that while the contractile effect of potassium chloride is obliterated by removal of extracellular calcium, a substantial proportion of the contractile effect of U44069 persists under these conditions. The persistent effect of U44069 under calcium-free conditions was not diminished by nifedipine (a slow calcium channel blocker) but was blocked by 2-n-butyl-3-dimethylamino-5,6-methylenedioxyindene (an intracellular calcium antagonist). These results provide experimental evidence for the proposal that U44069 contracts the aorta in the absence of extracellular calcium by mobilizing intracellular calcium.