bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertension and nutrition in the young: early intervention?
Authors: Weidman W. H.
Published: April 2011

The few studies, carried out on infants, children, and adolescents, relating blood pressure to sodium intake have shown a weak positive correlation in some but not all individuals. The effect of body size on blood pressure confounds the interpretation of the effect of dietary sodium on blood pressure. There appear to be sodium-sensitive and sodium-unsensitive infants, children, and adolescents and is probably genetically transmitted. Most infants, children, and adolescents in industrialized populations have a salt intake far greater than required, and reduction in dietary sodium is safe and may be beneficial to those individuals with a family history of primary hypertension.
Dietary fats and the management of hypertension
Authors: Iacono James M. , Dougherty R. M. , Puska P.
Published: April 2011

The role of dietary fat in human hypertension has been of interest recently. Examples of two intervention studies are presented to demonstrate this effect. One study was conducted at Beltsville, MD, and the other at North Karelia, Finland. Healthy people served as subjects for the experiments and the foods consumed by the subjects were typical for the regions. During the intervention periods the percentage of energy from dietary fats was lowered while the polyunsaturated fatty acids were increased. Total energy intake and salt intake were kept relatively constant. Systolic and diastolic blood pressure were decreased during the lowered fat, higher polyunsaturated fatty acids intake period and this effect was reversed during the switchback period. The data give strong support to the hypothesis that dietary fat is associated with blood pressure.
Renal medullary blood flow: its measurement and physiology
Authors: Cupples W. A.
Published: April 2011

The vasculature of the mammalian renal medulla is complex, having neither discrete input nor output. There is also efficient countercurrent exchange between ascending and descending vasa recta in the vascular bundles. These considerations have hampered measurement of medullary blood flow since they impose pronounced constraints on methods used to assess flow. Three main strategies have been used: (i) indicator extraction; (ii) erythrocyte velocity tracking; and (iii) indicator dilution. These are discussed with respect to their assumptions, requirements, and limitations. There is a consensus that medullary blood flow is autoregulated, albeit over a narrower pressure range than is total renal blood flow. When normalized to gram tissue weight, medullary blood flow in the dog is similar to that in the rat, on the order of 1 to 1.5 mL∙min−1∙g−1. This is considerably greater than estimated by the radioiodinated albumin uptake method which has severe conceptual and practical problems. From both theoretical and experimental evidence it ssems that urinary concentrating ability is considerably less sensitive to changes in medullary blood flow than is often assumed.
The effects of morphine on sympathetic transmission in the stellate ganglion of the cat
Authors: Bosnjak Z. J. , Seagard J. L. , Roerig D. L. , Kostreva D. R. , Kampine J. P.
Published: April 2011

The aim of this study was to investigate which of the processes involved in synaptic transmission are affected by morphine in concentrations comparable to those used during surgical procedures. The effects of morphine sulfate on ganglionic transmission were studied in the stellate ganglion of the cat using intracellular and extracellular recordings in vitro. The neurons of the stellate ganglion were depolarized using preganglionic nerve stimulation, postganglionic nerve stimulation, and intracellular stimulation before and after introduction of morphine sulfate (up to 20 μg/mL). Tissue concentrations of morphine were estimated using radiolabeled morphine. Axonal transmission and the excitability of the postganglionic neurons to direct intracellular stimulation was not affected at the concentrations of morphine studied. In addition, morphine had a dose-dependent depolarizing effect on the resting membrane potential of most of the neurons in the stellate ganglion. Such neuronal depolarizations alone could initially produce excitation in some cell populations, followed by inhibition, secondary to the membrane depolarization, leading to depression of sympathetic nerve activity. The overall ganglionic transmission as recorded using an evoked potential was biphasic. At low doses morphine facilitated transmission, while at larger doses morphine attenuated evoked potentials. These effects do not appear to be mediated through classical opiate receptors since they are not blocked by naloxone.
Verapamil potentiates vagally mediated sinoatrial chronotropic responses in dogs
Authors: Wallick Don W. , Stuesse Sherry L. , Valencic Frank , Fratianne Richard B.
Published: April 2011

A brief burst of electrical stimuli delivered to the vagus nerve during the cardiac cycle elicits a triphasic cardiac chronotropic response. The cardiac cycle length initially increases, then briefly decreases, and subsequently increases again. We studied the effects of a calcium channel blocking agent, verapamil, on these responses to vagal stimulation during sinoatrial nodal rhythm in anesthetized, open-chest dogs. Verapamil increased the basal cardiac cycle length only slightly; however, the primary cardioinhibition was accentuated approximately 40% (from 396 to 555 ms) by verapamil. Neither the acceleratory phase of this triphasic response nor the secondary cardioinhibition was significantly affected by verapamil. These results indicate that verapamil potentiates the initial action of acetylcholine at the sinoatrial node when the vagus is activated with brief stimuli.
Functional and anatomical variability of canine cardiac sympathetic efferent pathways: implications for regional denervation of the left ventricle
Authors: Janes R. D. , Johnstone D. E. , Brandys J. C. , Armour J. A.
Published: April 2011

To further elucidate the functional anatomy of canine cardiac innervation as well as to assess the feasibility of producing regional left ventricular sympathetic denervation, the chronotropic and (or) regional left ventricular inotropic responses produced by stellate or middle cervical ganglion stimulation were investigated in 22 dogs before and after sectioning of individual major cardiopulmonary or cardiac nerves. Sectioning the right or left subclavian ansae abolished all cardiac responses produced by ipsilateral stellate ganglion stimulation. Sectioning a major sympathetic cardiopulmonary nerve, other than the right interganglionic nerve, usually reduced, but seldom abolished, regional inotropic responses elicited by ipsilateral middle cervical ganglion stimulation. Sectioning the dorsal mediastinal cardiac nerves consistently abolished the left ventricular inotropic responses elicited by right middle cervical ganglion stimulation but minimally affected those elicited by left middle cervical ganglion stimulation. In contrast, cutting the left lateral cardiac nerve decreased the inotropic responses in lateral and posterior left ventricular segments elicited by left middle cervical ganglion stimulation but had little effect on the inotropic responses produced by right middle cervical ganglion stimulation. In addition, the ventral mediastinal cardiac nerve was found to be a significant sympathetic efferent pathway from the left-sided ganglia to the left ventricle. These results indicate that (i) the stellate ganglia project axons to the heart via the subclavian ansae and thus effective sympathetic decentralization can be produced by cutting the subclavian ansae; (ii) the right-sided cardiac sympathetic efferent innervation of the left ventricle converges intrapericardially in the dorsal mediastinal cardiac nerves; and (iii) the left-sided cardiac sympathetic efferent innervation of the left ventricle diverges to innervate the left ventricle by a number of nerves including the dorsal mediastinal, ventral mediastinal, and left lateral cardiac nerves. Thus consistent denervation of a region of the left ventricle can not be accomplished by sectioning an individual cardiopulmonary or cardiac nerve because of the functional and anatomical variability of the neural components in each nerve, as well as the fact that overlapping regions of the left ventricle are innervated by these different nerves.
Mechanism for the opioid-induced twitch potentiations of frog's skeletal muscle
Authors: Shetty Suraj S. , Frank George B.
Published: April 2011

The twitch-potentiating effects of opioids in the frog's skeletal muscle which are naloxone resistant and nonstereospecific were further studied. The rapid kinetics of the onset and of the offset (following washout) of the opioid effect indicates that the site for this action is the surface membrane of the muscle fibre. On the other hand, the lack of any twitch-potentiating effect by naloxone methylbromide, a quaternary derivative of naloxone, suggests that opioids which potentiate the twitch must enter the lipid phase of the membrane to act. Intracellular microelectrode experiments revealed no relation between the opioid effects on membrane electrical events and twitch potentiation. Blocking slow calcium channels with D-600 did not modify the opioid-induced twitch potentiation. The twitch potentiation was antagonized by increasing the extracellular calcium concentration, [Ca2+]0, to 8.64 mM. The effects of closely spaced multiple electrical pulses revealed that the opioids decreased the summated response relative to predrug controls. The results suggest that opioids facilitate the process of excitation–contraction coupling in the frog's skeletal muscle by the release of an additional amount of "trigger calcium" following a single electrical stimulus, thereby generating a potentiated twitch.
The modulation of sensory transmission through the medullary dorsal horn during cortically driven mastication
Authors: Kim Joong Soo , Bushnell M. Catherine , Duncan Gary H. , Lund James P.
Published: April 2011

During mastication, reflexes are modulated and sensory transmission is altered in interneurons and ascending pathways of the rostral trigeminal sensory complex. The current experiment examines the modulation of sensory transmission through the most caudal part of the trigeminal sensory system, the medullary dorsal horn, during fictive mastication produced by cortical stimulation. Extracellular single unit activity was recorded from the medullary dorsal horn, and multiple unit activity was recorded from the trigeminal motor nucleus in anesthetized, paralyzed rabbits. The masticatory area of sensorimotor cortex was stimulated to produce rhythmic activity in the trigeminal motor nucleus (fictive mastication). Activity in the dorsal horn was compared in the presence and absence of cortical stimulation. Fifty-two percent of neurons classified as low threshold and 83% of neurons receiving noxious inputs were influenced by cortical stimulation. The cortical effects were mainly inhibitory, but 21% of wide dynamic range and 6% of low threshold cells were excited by cortical stimulation. The modulation produced by cortical stimulation, whether inhibitory or excitatory, was not phasically related to the masticatory cycle. It is likely that, when masticatory movements are commanded by the sensorimotor cortex, the program includes tonic changes in sensory transmission through the medullary dorsal horn.
Effect of long-term Intralipid® administration in mice
Authors: Allen T. M. , Murray L.
Published: April 2011

Intalipid® was administered intravenously to mice at a level of 2 g kg−1 day−1 for 23 days. No alterations in phagocytic index, liver or spleen size were observed in the chronically injected mice as compared with control mice that received saline injections. Tissue distribution of 0.45 μm multilamellar liposomes of egg phosphatidylcholine:cholesterol (2:1) was similar in mice that had been chronically injected with Intralipid® to that in control mice. Mice chronically given the same total amount of phospholipid in the form of 0.2 μm liposomes of phosphatidylcholine:cholesterol (2:1) rather than as a lipid-triglyceride emulsion showed altered tissue distribution of entrapped label with decreased liver uptake and increased splenic uptake, which is indicative of reticuloendothelial blockade. Tissue distribution of [14C]dipalmitoylphosphatidylcholine Intralipid® was compared with that of [14C]dipalmitoylphosphatidylcholine 0.2 μm MLV of phosphatidylcholine:cholesterol (2:1). Intralipid® was taken up 2- to 3-fold less by liver and 5- to 10-fold less by spleen than liposomes. Blood levels of Intralipid® were higher than those of liposomes. [14C]dipalmitoylphosphatidylcholine Intralipid® was eliminated from the body at a faster rate than [14C]dipalmitoylphosphatidylcholine liposomes. The lack of reticuloendothelial blockade caused by Intralipid® as compared with liposomes appears to be related to its diminished uptake into reticuloendothelial tissues. This diminished uptake may be related to differences in apolipoprotein uptake of Intralipid®, which is primarily in the form of a phospholipid monolayer, and liposomes, which have their phospholipid organized into a bilayer.
Central integration of cardiovascular and drinking responses elicited by central administration of angiotensin II: divergence of regulation by the ventral tegmental area and nucleus accumbens
Authors: Jones D. L.
Published: April 2011

Previous studies had implicated the involvement of the ventral tegmental area and its dopamine projections to the nucleus accumbens in goal-directed behavior. This study investigated whether or not the GABAergic inputs to the ventral tegmental area and, in turn, dopaminergic input to the nucleus accumbens from the ventral tegmental area modify drinking and cardiovascular responses elicited by central administration of angiotensin II. Injections of 25 ng of angiotensin II into a lateral cerebral ventricle of the rat elicited water intakes averaging 7–8 mL in 15 min with latencies usually less than 3 min. Pretreatment of the nucleus accumbens with spiperone, a dopamine antagonist, or the ventral tegmental area with γ-amino butyric acid (GABA) produced dose-dependent reductions in water intake and number of laps taken while increasing the latency to drink. The spiperone injection did not alter the pressor response. On the other hand, the GABA injections attenuated the pressor responses to central angiotensin II administration. These findings suggest that GABA input to the ventral tegmental area modifies both the cardiovascular and drinking responses elicited following central administration of angiotensin II. However, the dopamine projections to the nucleus accumbens appear to be involved only in the drinking responses elicited by central injections of angiotensin II. Divergence for the coordination of the skeletal motor behavioral component and the cardiovascular component elicited by central administration of angiotensin II must occur before the involvement of these dopamine pathways.
Neuronal experience modifies synaptic long-term facilitation
Authors: Pahapill P. A. , Lnenicka G. A. , Atwood H. L.
Published: April 2011

In a crayfish phasic neuromuscular junction, we have demonstrated low-frequency depression (LFD), high-frequency depression (HFD), and long-term facilitation (LTF) in response to different regimens of stimulation. Chronic stimulation of the phasic axon supplying the closer muscle of the claw in Procambarus clarkii resulted in diminished expression of HFD and LTF. Conversely, when impulse production in the phasic motoneuron was reduced by claw immobilization, both HFD and LTF were enhanced. LFD was insensitive to these manipulations. These results provide further evidence for long-term adaptation of the phasic neuromuscular junction to ongoing levels of impulse activity and illustrate the importance of a neuron's past history for synaptic plasticity. The ability of the neuron to adjust its short-term plasticity in response to altered experience constitutes an adaptive response that could be of general significance.
Effects of diet and thermal acclimation on oxygen consumption in rats
Authors: Pinto F. N. Santos , Tarasantchi J. , Griggio M. A.
Published: April 2011

The relationship between food intake and oxygen consumption was studied in a group of 60 rats acclimated at environmental temperatures of either 30 or 10 °C. Three separate experiments were performed. In the first, 28 rats were divided into two groups: control, which received 20 and 32 g of food/day at 30 and 10 °C, respectively, from 0800 to 1700 and experimental, which received 10 and 25 g of food/day at 30, and 10 °C, respectively. The experimental period lasted 6 weeks. Oxygen consumption was measured weekly at environmental temperatures of 5, 15, 25, 30, and 35 °C. In the second experiment, 16 rats were subjected to the same food intake as the animals in the first experiment. After 1 week, their oxygen consumption was measured at 25 °C over a period of 24 h. The third experiment was carried out with 16 other rats in which the control groups received the same amount of food as in the first experiment, and the experimental groups were fed 6 and 11 g/day at 30 and 10 °C, respectively, during 1 week. In the first experiment, no changes in oxygen consumption (per kilogram 0.67) were apparent in the experimental rats during 6 weeks. However, after 1 week on severe food restriction a significant decrease in oxygen consumption (per kilogram 0.67) was observed. A long-lasting thermic effect of food was observed in control rats from the second experiment and a rapid effect was apparent in restricted rats. The results seem to indicate that in the rat, although the oxygen consumption does depend on the level of food intake, it is necessary to have a higher level of restriction to make it apparent when compared with larger species of animals. It is also suggested that energy conservation mechanisms did not interfere with cold acclimation.
In vivo simultaneous comparison of pressor and uterine responses to a single agonist (oxypressin) in estrous rats
Authors: Gazis Diana , Gonzalez Geneviève , Mendlowitz Milton
Published: April 2011

To try to compare receptor compartment kinetics, receptor binding, and binding–response coupling for two smooth muscle types in vivo, pressor and uterine responses to oxypressin, an equipotent analog of oxytocin and vasopressin, were studied simultaneously in urethane-anesthetized, pentolinium–indomethacin treated rats. Access of peptide to the pressor and uterine receptor compartments and peptide–receptor dissociation rate had a negligible effect on the two responses. During both injections and infusions, the blood pressure response seemed to be determined largely by plasma levels of oxypressin. The uterine response to oxypressin, however, was paradoxical. The heights of individual uterine contractions seemed to be determined throughout by plasma oxypressin concentrations. The interval between contractions also seemed to be determined by plasma peptide concentrations during injections. However, as plasma peptide increased and reached steady state during infusion, contraction interval behaved as if plasma peptide concentrations were decreasing. This effect was more marked at the beginning of infusion. The implication of these results is that binding determines the pressor response to oxypressin and binding–response coupling does not change. In contrast, although binding determines the uterine response to oxypressin during injection and binding–response coupling appears constant, some factor in addition to binding affects the contraction interval portion of the uterine response and modifies the apparent binding–response coupling of this parameter during infusion.
Effects of cold storage on relaxation responses in the rat oesophageal tunica muscularis mucosae
Authors: Akbarali H. , Bieger D. , Triggle C. R.
Published: April 2011

Tetrodotoxin-resistant relaxations produced by electrical field stimulation, 5-hydroxytryptamine (5-HT), and A23187 (calimycin) were investigated in the rat isolated oesophageal tunica muscularis mucosae subjected to cold storage of varied duration. Cold storage for 2 days abolished cholinergic nerve mediated contractions to field stimulation; however, field stimulation evoked relaxations and muscarinic agonist evoked contractions persisted undiminished. After 5 days of cold storage, field-stimulated relaxations, as well as tension generating capacity of the tissue, were significantly reduced. Proximodistal differences were observed in tunica muscularis mucosae sensitivity to the relaxant effects of serotonin and A23187 and these were exaggerated after cold storage. In the distal segment, cold storage for 2 days unmasked ketanserin-sensitive 5-HT receptors mediating contractions. Similarly, A23187 induced contractions rather than relaxation in cold-stored distal tunica muscularis mucosae; however, this effect was resistant to ketanserin. Immunohistochemical staining by means of the peroxidase–antiperoxidase technique revealed 5-HT-like immunoreactive "mast cells" within the tunica muscularis mucosae. These cells appeared to be associated with the smooth muscle rather than the vasculature. It is concluded that (i) field-stimulated relaxation is not dependent on intramural nerves, and (ii) it is unlikely that the release of 5-HT from mast cells or other cells mediates field-stimulated relaxation. However, confirmation awaits the provision of an antagonist against the novel 5-HT receptor that mediates 5-HT-induced relaxations.
Effects of acute changes in load and inotropic state on the exponential rate of fiber shortening and other indices of myocardial contractility in the anesthetized intact dog
Authors: Lezo José Suarez de , Casey Pierre , Casey Anita , Carrasco José Luis , Arizon José M. , Cantalapiedra Ignacio A. , Gattiker Harry F.
Published: April 2011

The effects of an acute increase in preload, afterload, and inotropic state on several indices of left ventricular contractility were studied in 20 anesthetized intact dogs. The behaviour of the exponential rate of fiber shortening (ERFS), a newly described index, which is based on the instantaneous fiber length – time relationship through ejection, was compared with other classical ejection and isovolumic indices of left ventricular contractility. Acute volume overload by dextran 40 infusion produced a significant increase in preload as reflected by a 103% (p < 0.01) increase in left ventricular end-diastolic pressure and a 121% (p < 0.001) increase in end-diastolic circumferential wall stress. There was also a smaller but significant increase (p < 0.05) of heart rate (30%) and of peak systolic circumferential wall stress (24%). None of the left ventricular contractility indices showed any significant change. Acute pressure overload, produced mechanically by an aortic balloon, increased the afterload significantly as reflected by a 33% (p < 0.05) rise of end-systolic circumferential wall stress and a 43% (p < 0.001) increase in systemic resistance. Stroke volume decreased significantly by 23% (p < 0.05). All ejection indices, including ERFS, were significantly diminished by 30 – 37%; all isovolumic indices showed no significant changes. Positive inotropic intervention was induced by dopamine infusion, which caused a significant 28% (p < 0.05) increase in cardiac output. End-diastolic and end-systolic circumferential wall stress were significantly diminished. All indices of left ventricular contractility increased significantly and ERFS showed the quantitatively greatest change. This study suggests that ERFS is an ejection index of myocardial contractility, which is quite sensitive to inotropic intervention, independent of preload but sensitive to afterload.
Comparison of the specific binding of cortisol in human amnion, amniotic fluid, and plasma
Authors: Riopel L. , Gibb W.
Published: April 2011

The purpose of this study was to compare the specific cortisol-binding protein found associated with human amnion with specific cortisol binding in human amniotic fluid and plasma. The electrophoretic mobility on polyacrylamide gels of the specific cortisol binding in amnion, amniotic fluid, and maternal plasma was identical. The influence of pH on cortisol binding activity was similar in all tissues and the cortisol binding was immunoprecipitable by a polyclonal antibody raised against human corticosteroid-binding globulin. The interaction of the cortisol binding protein with concanavalin A was studied in preterm amniotic fluid, term amniotic fluid, term amnion, and plasma from pregnant women at term and women under oral contraceptive treatment. Binding to concanavalin A was similar in term amnion and term amniotic fluid but was less than that found with both preterm amniotic fluid and term plasma. These results indicate that the cortisol binding portein associated with human amnion has similar characteristics to plasma corticosteroid-binding globulin, but that its state of glycosylation appears to be more like that of the cortisol binding protein in term amniotic fluid rather than in plasma.
Effect of cyclooxygenase and thromboxane synthetase inhibition on furosemide-stimulated plasma renin activity
Authors: Datar Sunil , McCauley Frances A. , Wilson Thomas W.
Published: April 2011

We studied the effects of a specific thromboxane (TX) synthetase inhibitor (U-63,557A) and a cyclooxygenase inhibitor on furosemide-induced renin release. Furosemide (2.0 mg∙kg−1) was injected into Sprague–Dawley rats pretreated with indomethacin (10 mg∙kg−1, i.v.), U-63,557A (1.0–32.0 mg∙kg−1, i.v.), or vehicle (Na2CO3 0.03 M). Plasma renin activity was measured in blood samples collected 0, 10, 20, and 40 min after the injection of furosemide. Blood was also collected after the administration of vehicle, indomefhacin, or U-63,557A for serum TXB2, a measure of platelet TXA2 synthesis. The results demonstrated that plasma renin activity rose with time following furosemide in the various groups of rats; indomethacin suppressed the furosemide-induced increments in plasma renin activity, while U-63,557A at doses of 4–8 mg∙kg−1 augmented it. At doses below 4 mg∙kg−1 or above 8 mg∙kg−1, U-63,557A did not augment renin secretion. Indomethacin and U-63,557A reduced serum thromboxane by 81 and 90%, respectively. Thus, these experiments suggest that thromboxane synthetase inhibition, within a narrow dosage range, potentiates furosemide-induced renin release while cyclooxygenase inhibition suppresses it.
Evidence for Des-Tyr1-D-Ala2-leucine5-enkephalinamide calcium agonist activity in vascular smooth muscle
Authors: Given Michael B. , Sander Gary E. , Giles Thomas D.
Published: April 2011

Intravenous administration of the enkephalin analog Des-Tyr1-D-Ala2-Leu5-enkephalinamide (DTALE) to conscious dogs produces a pressor response that is not inhibited by naloxone. In an attempt to explain this observed pressor activity in vivo, the effect of DTALE on vascular smooth muscle was investigated in vitro. DTALE was found to contract rat thoracic aorta strips in a dose-dependent and naloxone-insensitive manner. Pretreatment with reserpine (5 mg/kg) or prazosin was without significant effect. However, a significant inhibition was obtained with cyproheptadine (p < 0.001, n = 5), a 5-hydroxytryptamine (5-HT) receptor antagonist that also has calcium channel blocking activity. Treatment with ketanserin (0.1 μM), a selective 5-HT2-receptor antagonist, had no effect. Reduction of the extracellular calcium concentration from 1.6 to 1.2 mM or 0.8 mM significantly diminished DTALE activity (1.2 mM, p < 0.025; 0.8 mM, p < 0.01; n = 3). Pretreatment with the calcium channel antagonists verapamil (0.1 μM) and nitrendipine (0.05 μM) significantly inhibited DTALE activity (p < 0.001 for both treatments). DTALE also exhibited increased potency in partially depolarized smooth muscle preparations. These results suggest that DTALE may produce vasoconstriction by inducing or facilitating calcium influx. This activity upon arterial vascular strips may provide explanation for the observed pressor response in chronically instrumented conscious dogs.
The effects of gestational age and intrafetal ACTH administration on the concentration of progesterone in the fetal membranes, endometrium, and myometrium of pregnant sheep
Authors: Power S. G. A. , Challis J. R. G.
Published: April 2011

To examine the hypothesis that progresterone withdrawal from intrauterine tissues is a prerequisite to spontaneous labour or labour induced by administering ACTH to the ovine fetus, we measured the concentration of progesterone in amnion, chorion, endometrium, and myometrium of sheep at different stages of pregnancy and during ACTH-induced labour. There was no significant change in the concentration of progesterone nor in the progesterone:estradiol ratio in amnion or chorion in association with either spontaneous or ACTH-induced labour. The concentration of progesterone in endometrium rose significantly between days 50–60 and days 130–135 of gestation and decreased at term. There was also a fall in the progesterone.estradiol ratio in endometrium between days 130–135 and term. Neither the progesterone concentration not the progesterone:estradiol ratio changed in endometrium during ACTH-induced labour. In the myometrium the concentration of progesterone rose significantly between days 50–60 and day 100 of pregnancy and decreased between day 100 and days 130–135, with a further decline towards term. After intrafetal ACTH there was no change in the concentration of progesterone in the myometrium, although there was a fall in the progesterone:estradiol ratio. We conclude that labour occurring spontaneously at term is associated with a decrease in the progesterone concentration of maternal intrauterine tissues, the myometrium and endometrium. In contrast, there is no decline in the progesterone concentrations of the fetal membranes, the amnion and chorion. The changes in the progesterone concentrations of myometrium and endometrium were not reproduced at labour provoked by ACTH administration to the fetus. Thus, although progesterone withdrawal from the myometrium and endometrium may occur in association with late pregnancy, this change does not appear to be an essential prerequisite to birth.
Electrophysiological evidence for ammonium as a substitute for potassium in activating the sodium pump in a crayfish sensory neuron
Authors: Moser Hans
Published: April 2011

Electrophysiological studies were performed on slowly adapting cells of the crayfish (Astacus astacus) stretch receptor to examine some aspects of the operation of the sodium pump. Intracellular sodium activity [Formula: see text] and pH (pHi) were measured with liquid ion exchanger microelectrodes and the effects of [Formula: see text] were observed. In cells in which the sodium pump was inhibited by K+-free solution, [Formula: see text] induced a decrease of [Formula: see text] that can be explained only if Na+ extrusion is assumed. pHi measurements provide indirect evidence that [Formula: see text] was taken up at the same time as Na+ was extruded. Ouabain blocks the operation of the sodium pump in the presence of K+ and [Formula: see text]. This result suggests that the ammonium-mediated decrease in [Formula: see text] in K+-free solution was caused by activation of the sodium pump. The results obtained by electrophysiological methods in a living cell are qualitatively in good agreement when compared with biochemical investigations on assays of crustacean Na+–K+ ATPase.
Gender differences in cardiovascular and metabolic responses to cold and exercise
Authors: Stevens Glen H. J. , Graham T. E. , Wilson B. A.
Published: April 2011

This study was conducted because of the paucity of information concerning gender differences in the cardiovascular and metabolic responses to cold stress. Lightly clad men (n = 8) and women (n = 8) were tested in 21 and 5 °C environments during a 20-min rest, followed by 20 min each of 50, 100, and 150 W of exercise. At 21 °C there was no gender differences in [Formula: see text] or cardiac output. Cold lowered skin temperature more in women than in men, but women demonstrated no differences in heart rate, stroke volume, or [Formula: see text] at 5 and 21 °C. The women's noradrenaline levels in the cold were higher than comparable 21 °C data at rest and 50 W and increased with work intensity in both tests. In contrast, men had a lower heart rate, higher stroke volume, and higher [Formula: see text] throughout the 5 °C treatment compared with 21 °C. The men's noradrenaline response to 5 °C was similar to that of women at rest and 50 W, but the level subsequently declined at 100 and 150 W. Thus, the women do not show a heart rate – stroke volume shift in either resting or exercising states in cold environments. Furthermore, the data fail to support that either skin cooling or changes in noradrenaline cause the bradycardia and enhanced stroke volume seen in men.
Left ventricular catecholamines during acute myocardial infarction in the dog
Authors: Kaufman W. Reuben , Jugdutt Bodh I.
Published: April 2011

To determine whether changes in left ventricular catecholamine content occur during the first 30 to 90 min of acute myocardial infarction, myocardial catecholamine (radioenzymatic assay) over the interval was studied in the dog. In nine pentobarbital-anesthetized opened-chest dogs without coronary ligation, myocardial catecholamine at 2.5 h after pentobarbital (i) consisted mainly of norephinephrine (87% total catecholamine), (ii) showed a base to apex gradient in norephinephrine (1.44 ± 0.10 vs. 1.03 ± 0.10 μg/g, p < 0.05) and dopamine (0.20 ± 0.03 vs. 0.12 ± 0.02 μg/g, p < 0.05) but not epinephrine (0.017 vs. 0.016 μg/g), and (iii) showed no difference in norepinephrine, dopamine, or epinephrine across basal, mid, and apical left ventricular transverse planes spanning the vascular territories of the two coronary arteries. In 18 pentobarbital-anesthetized dogs with coronary ligation, (i) norepinephrine, measured in 14 regions across the mid left ventricle after 90 min ischemia in four dogs, was less in the ischemic center of the occluded bed than normal myocardium (1.01 ± 0.04 vs. 1.29 ± 0.04 μg/g, p < 0.05), and (ii) norepinephrine was unchanged in normal myocardium of 14 dogs at 30, 60, 90 min, and 48 h but decreased in ischemic myocardium by 31% at 60 min (0.89 ± 0.10 vs. 1.29 ± 0.08 μg/g, p < 0.025) and 79% at 48 h (0.27 ± 0.04 vs. 1.26 ± 0.08 μg/g, p < 0.001). Thus, norepinephrine depletion from ischemic but not normal myocardium is detectable by 60 min during acute myocardial infarction.
Inotropic responses of the left ventricle to changes in heart rate in anesthetized rabbits
Authors: Bell Leonard B. , Peterson D. Fred
Published: April 2011

Factors known to influence left ventricular contractility include preload, afterload, circulating catecholamine concentration, efferent sympathethic discharge, and heart rate. Heart rate influences have been primarily determined in the dog, whereas the influence of heart rate in smaller mammals has not been determined. Eight pentobarbital-anesthetized rabbits were instrumented to measure electrocardiogram, heart rate, left ventricular pressure, end-diastolic pressure, dP/dt, and mean and pulsatile aortic pressures. Systematic bradycardia was induced by stimulating the peripheral end of the sectioned right vagus nerve. Between 293 and 235 beats/min, there was no change in (dP/dt)max as heart rate was decreased. Below this range there was a direct relationship between (dP/dt)max and heart rate. Preload remained unchanged down to 132 beats/min. There was a small but significant decrease in afterload (0.09 mmHg∙beat−1∙min−1; 1 mmHg = 133.32 Pa) throughout the decrease in heart rate. Infusion of propranolol (2.0 mg/kg) produced no marked change in the heart rate – (dP/dt)max relationship, although both resting heart rate and (dP/dt)max were reduced. This study demonstrates that (dP/dt)max is not influenced by changes in heart rate above 235 beats/min in the pentobarbital-anesthetized rabbit. These results differ from findings in other animals, and demonstrate that species and heart rate ranges must be considered when drawing conclusions regarding (dP/dt)max as a reliable index of contractility.
A novel analysis of fetal breathing
Authors: Ioffe S. , Jansen A. H. , Chernick V.
Published: April 2011

We have analyzed a variety of approaches in assessing fetal breathing parameters (VT, T1, Ttot, VT/TI, V1) in eight fetal sheep during a control period and during stimulation with 6 and 9% CO2. By using conventional analysis of data blocks varying from 100 to 1500 breaths, several different conclusions could be reached regarding the respiratory response to hypercapnia: stimulation, depression, or no change in all parameters studied. A new analysis based on piecewise linear regression used as a data grouping technique indicated that a simple mean ± SD of the individual parameters was an inappropriate description of normal or stimulated fetal breathing. Based on tests for homogeneity of regressions of VT on T1 for a completely random design, it is concluded that an estimate of fetal respiratory drive is only described adequately by two to four regression regimes. These regimes, estimated from the regression technique, could be combined to give a weighted mean value based on the proportion of time they were present. Using this new approach and an analysis of variance, we found (i) that frequency and V1 were similar between animals during control and hypercapnia, (ii) that breathing frequency decreased during hypercapnia, and (iii) a positive relationship between VT and TI.
The diffusion and electrogenic components of the membrane potential of hypoxic myocardium
Authors: Leblanc Normand , Ruiz-Ceretti Elena
Published: April 2011

The diffusion and electrogenic components of the resting potential of hypoxic ventricular muscle were separated by inhibition of the sodium pump with 10−4 M ouabain. The response to varying external K concentrations (Ko) was studied. Arteriaily perfused rabbit hearts were submitted to 60 min hypoxia in Krebs solution containing 5 mM K throughout or to different external K concentrations during the last 20 min of hypoxia. For K concentrations between 1.5 and 10 mM, hypoxia did not change the resting potential except for a slight hyperpolarization in 7.5 mM K. The diffusion component of the resting potential did not differ from the resting potential at Ko < 5 mM. An electrogenic potential of −3 to −6 mV was detectable at Ko values between 5 and 10 mM. The internal K concentration, Ki, was estimated from extrapolations to zero potential of the relation resting potential vs. Ko in normoxic and hypoxic hearts. These experiments revealed a decline of Ki of 16 mM with hypoxia. The variation of the diffusion potential with external K was fitted by a PNa:PK ratio five times lower than in normoxia. It has been concluded that an increase in K permeability and the persistence of electrogenic Na extrusion during hypoxia of rather short duration prevent membrane depolarization despite the myocardial K loss.
Relationship of urotensin I induced vasodilatory action in rat thoracic aorta to Ca2+ regulation
Authors: Itoh H. , Lederis K.
Published: April 2011

The relaxant effects of the synthetic fish neuropeptide urotensin I were examined in helical strips of rat aorta. In K+-depolarized aorta strips, urotensin I and verapamil competitively inhibited Ca2+-induced contractions. Urotensin I relaxed, in a concentration-dependent manner, the contraction produced by the Ca2+ ionophore A23187, whereas verapamil had no effect on this contraction, even at a concentration of 10−5 M. In the absence and presence of extracellular Ca2+, urotensin I inhibited both components of the contractions elicited by norepinephrine or urotensin II, another fish neuropeptide. Verapamil reduced only the norepinephrine or urotensin II induced contraction in the presence of extracellular Ca2+, with little or no change in the contraction in Ca2+-free buffer. The urotensin I induced relaxation response in aortic strips contracted by 40 mM KCl was enhanced by pretreatment with papaverine or forskolin. Pretreatment with dibutyryl cAMP did not significantly alter the action of urotensin I. The presence or absence of endothelial cells did not change the response to urotensin I. These results suggest that urotensin I antagonizes the action and (or) mobilization of extracellular and intracellular Ca2+.
The role of the mast cell in allergic bronchospasm
Authors: Befus D.
Published: April 2011

In allergic bronchospasm inhaled allergen interacts with specific IgE antibody on the surface of mast cells, inducing the release of mediators, particularly histamine and leukotrienes, which induce bronchoconstriction. Disodium cromoglycate, previously considered to be predominantly a mast cell stabilizing agent, is effective prophylactically in inhibition of early and late phase asthmatic reactions. However, the microenvironment of the airways contains many cell types and the precise role of mast cells is not clear. Lymphocytes, alveolar macrophages, eosinophils, platelets, and neutrophils possess low affinity surface receptors for IgE and can respond to allergen, releasing mediators that have diverse functions. These observations compound the problem of which mediator(s) is most important in pathogenesis of asthma. Moreover, mast cell products modulate the functions of many cells, and thus whether mast cells act directly or indirectly on bronchial smooth muscle requires clarification. Neuropeptides activate or modulate mast cells, and together with evidence of the close association of mast cells and nerves, these observations provide exciting new directions for investigation. Evidence that mast cells from different sites are heterogeneous in their response to stimuli and antiallergic drugs and differ in mediator production and function amplifies the problems identified above. In summary, the role of mast cells in bronchoconstriction is complex and systematic analysis of interactions between mast cells and other cells of the airways is essential.
Studies on the mechanism of action of diallyl sulfide, an inhibitor of the genotoxic effects of cyclophosphamide
Authors: Goldberg Mark T. , Josephy P. David
Published: April 2011

Diallyl sulfide, a component of garlic oil, has been previously shown to inhibit induction of nuclear aberrations in the colons of mice treated with 1,2-dimethylhydrazine, a colon carcinogen. The ability of this agent to block cyclophosphamide-induced nuclear aberrations in urinary bladder and hair follicles was tested. [14C]Cyclophosphamide was injected and urine was collected to determine the disposition of metabolites of cyclophosphamide in mice treated with diallyl sulfide. This agent was capable of blocking nuclear aberration induction by cyclophosphamide in bladder and hair follicles. The effect was not mediated through inhibition of mitosis as determined by [3H]thymidine autoradiography in hair follicles. Diallyl sulfide pretreatment decreased the amount of radioactivity excreted in the urine in the first 24 h following cyclophosphamide treatment and blocked the appearance of acrolein, a cytotoxic metabolite of cyclophosphamide, in the urine over this time period. These results suggest that diallyl sulfide acts by conjugating the toxic metabolites of cyclophosphamide, thereby limiting their systemic circulation and diverting their route of excretion from the urine.
Use of intermediate endpoints in quantitating the response of precancerous lesions to chemopreventive agents
Authors: Rosin Miriam P. , Dunn Bruce P. , Stich Hans F.
Published: April 2011

A current area of emphasis in cancer research is the determination of whether cancer can be prevented through the use of naturally occurring chemopreventive agents such as β-carotene. A major area of concern in the design of long-term, large-scale population studies to ascertain the efficacy of such chemopreventive agents lies in the paucity of biological data on the activity of these agents in man. The studies described in this paper were performed to determine whether a series of short-term markers could be used in chemopreventive trials as indicators of the possible success of a chemopreventive regime. Three such markers are described. The first involves the measurement of genotoxic damage in the target tissues of carcinogen-exposed individuals by using the micronucleus test on exfoliated cells. This end point has been successfully used to demonstrate a reduction in carcinogen damage (micronuclei production) in the oral cavity of individuals in population groups at elevated risk for oral cancer (tobacco and betel quid users in the Philippines, snuff users in the Northwest Territories). The second marker involves the determination of DNA adducts in exfoliated cells of carcinogen-exposed individuals by the use of DNA postlabelling procedure. The final marker discussed involves a chemical determination of the levels of a chemopreventive agent in target tissues of individuals receiving a supplement in the diet. In this case, the example described is β-carotene in exfoliated cells of carcinogen-exposed individuals. These three markers may be combined to determine whether a chemopreventive agent reaches a target tissue, affects DNA adduct formation, and prevents genotoxic damage. Whether agents effective using these end points will also produce a response in preventing or reversing premalignant lesions is currently under investigation.
Increased incidence of isoproterenol-induced ventricular fibrillation in aging rats
Authors: Guideri Giancarlo , Olivetti Giorgio , Hiler Beth , Ricci Roberto , Anversa Piero
Published: April 2011

Prolonged β-adrenergic stimulation obtained by subcutaneous injection of isoproterenol in unanesthetized, unrestrained rats elicited ventricular fibrillation in approximately 80% of animals at 10–12 months of age. Ventricular fibrillation failed to occur in 1-month-old rats and involved only 12% of rats at 2 months. Senescence appeared not to increase the frequency of ventricular fibrillation since a similar incidence was seen in rats at 10–12 and 19–21 months. In all instances, ventricular fibrillation was preceded by ECG changes consistent with acute subendocardial ischemia. To evaluate whether acute β-adrenergic stimulation elicits comparable cardiovascular effects in animals of different age, a dose–response curve to intravenous injection of isoproterenol was performed in anesthetized rats. Changes in heart rate, systemic arterial pressure, left ventricular pressure, and dP/dt were not different among animal groups. It was concluded that the arrhythmogenic potential of isoproterenol may not be related to differences in cardiac β-receptor sensitivity with age as suggested by the comparable changes in the inotropic and chronotropic actions of isoproterenol in the animal groups studied.