bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose-dependent effects of arginine vasopressin on endocrine and blood gas responses of fetal sheep during the last third of pregnancy
Authors: Norman Laurie J. , Challis John R. G.
Published: April 2011

Arginine vasopressin (AVP) is released in fetal sheep in response to various intrauterine stresses such as hypoxaemia, hypotension, and haemorrhage. We have examined the effects of exogenous AVP injected at two doses (200 ng and 2 μg) on the plasma concentrations of ACTH and cortisol, and on arterial blood [Formula: see text], [Formula: see text], and pH in chronically catheterized fetal sheep at d110–115, d125–130, and at d135–140 of pregnancy. AVP (2 μg) provoked a significant elevation in the plasma ACTH and cortisol concentration at all three stages of gestation, whereas the administration of 200 ng AVP raised plasma ACTH and cortisol only at d110–115 and at d 125–130. The increment in plasma cortisol after 200 ng AVP at the two earlier stages of pregnancy was similar to that after 2 μg AVP, despite a dose-dependent difference in the change in ACTH concentration. AVP stimulated a rise in [Formula: see text] at each time of study, although the time course of response was shorter at d135–140 than at the previous stages of pregnancy. The effect of AVP on [Formula: see text] was more variable, showing a transient decrease at +5 min after injection in the two oldest groups of fetuses. pH fell after AVP at dl 10–115 and at d125–130, but it rose transiently in the oldest fetuses. We conclude that at high concentrations systemic administration of AVP provokes endocrine and blood gas changes in fetal sheep. ACTH was consistently elevated by AVP. [Formula: see text] also rose at each stage of pregnancy, but the effects on [Formula: see text] and pH varied as a function of fetal age. Our results support other studies that suggest a role for AVP in the responses of the fetus to intrauterine stresses such as hypoxia.
Functional origin of rate-induced changes in atrioventricular nodal conduction time of premature beats in the rabbit
Authors: Billette Jacques , St-Vincent Marie
Published: April 2011

The characteristics and origin of the rate-induced changes in atrioventricular nodal conduction time of premature beats (A2H2 intervals) were studied in isolated rabbit heart preparations. Increasing the basic driving rate during a periodic premature stimulation prolonged (a net inhibitory effect) and shortened (a net facilitatory effect) significantly (p < 0.01, n = 17) the A2H2 intervals associated with long and short recovery times (H1A2 intervals), respectively. The origin of these responses was sought for by analyzing interactions between facilitation and fatigue. When the fatigue developed at a fast basic rate was estimated from changes in conduction time of basic beats and subtracted from the corresponding A2H2 intervals, the calculated A2H2 intervals showed enhanced facilitation but no fatigue. When independently obtained fatigue and facilitation effects were added to the control A2H2 intervals for corresponding H1A2 intervals, resulting A2H2 intervals correlated strongly with the ones observed at the equivalent fast basic rate (r = 0.99, p < 0.001). Moreover, changes in the A2H2 intervals of premature beats tested with constant coupling intervals during 5-min fast rates were biphasic, confirming the overlapping and competition between facilitation and fatigue effects. Hence, rate-induced deviations of premature nodal conduction time from that predicted by changes in recovery time are consistent and result from the interaction between the overlapping effects produced by two independent, antagonist, and dynamically distinct nodal properties (facilitation and fatigue).
In vitro inhibition of calcium binding by alloxan and of calcium transport by isolated vascular smooth muscle microsomes
Authors: Kwan C. Y. , Beazley J. S.
Published: April 2011

The primary purpose of this study was to investigate the possible direct toxic effect of alloxan on the Ca2+ handling by microsomal membranes isolated from rat mesenteric arteries. It was found that preincubation of the vascular muscle microsomal membranes with alloxan had a suppressive effect on both binding of Ca2+ (in the absence of ATP) and ATP-supported Ca2+ transport. Such an inhibition was time, dose, pH, and temperature dependent. ATP-surpported Ca2+ transport was more susceptible to the inhibitory action of alloxan than Ca2+ binding. Unlike alloxan, another commonly used diabetogenic drug, streptozotocin, was not effective in causing such an in vitro inhibition of Ca2+ handling.
Plasma parathyroid hormone during the development of spontaneous hypertension in rats
Authors: Pang P. K. T. , Harvey S. , Doris P. A.
Published: April 2011

Plasma parathyroid hormone levels (pPTH) have been measured by radioimmunoassay (RIA) in young spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto controls (WKY) aged from 6 to 16 weeks to assess the possible role of PTH during the development of hypertension. Three antisera were used in the RIAs. One antiserum was directed toward the inactive C-terminal fragment of PTH, another toward the bioactive N-terrninal fragment (PTH 1–34), and a third was obtained by immunization against intact PTH 1–84. Blood pressures were measured by tail-cuff plethysmography with prewarming. Blood ionized calcium and sodium concentrations (b[Ca2+] and b[Na+]) were determined by ion-selective electrolyte analysis. No significant differences were observed between pPTH in the SHR compared with WKY during the development of hypertension. Neither were significant differences in b[Ca2+] or b[Na+] present at any age. The expected progression of hypertension in SHRs was observed and blood pressure was significantly greater in SHR than in WKY at all times. The results suggest that differences in pPTH and b[Ca2+] in SHR reported in other studies may be secondary phenomena to the establishment of hypertension. Our data suggest that PTH is not involved in the pathogenetic processes occurring during the development of spontaneous hypertension in rats.
Qualitative measurements of the entry of L-lactate into single surface fibres of frog skeletal muscle using a lactate-sensitive microelectrode
Authors: Mason M. J.
Published: April 2011

The present results demonstrate the sensitivity of the Corning chloride liquid ion exchanger 477913 to L-lactate. Microelectrodes filled with this exchanger showed responses to changes in L-lactate concentration in chloride-free solutions. In these experiments L-lactate replaced gluconate in equimolar amounts. Microelectrodes filled with this exchanger were used to qualitatively detect changes in intracellular anion in chloride-depleted frog sartorius muscle fibres during exposure to extracellular concentrations of L-lactate. The increase in intracellular anion concentration is consistent with the movement of L-lactate into the cell. This microelectrode enables one to qualitatively monitor changes in intracellular L-lactate in chloride-free experiments without incorporating selectivity coefficients.
Adrenomedullary origin of the hindquarter vasodilation during the transposition response of the rat
Authors: Sakata S. , Iriuchijima J.
Published: April 2011

Transposing a rat from the home cage to a new cage produces a cardiovascular response (transposition response) characterized by an increase in hindquarter blood flow with unchanged systemic arterial pressure. Arterial blood samples were collected from rats before and during this response for radioenzymatic assay of catecholamines. During the transposition response, the concentration of adrenaline and noradrenaline in plasma increased about six- and two-fold, respectively. Ablation of the adrenal medulla prevented these changes in plasma catecholamine concentration. Constant i.v. infusion of adrenaline, at rates producing a hindquarter flow approximately matching that observed during the transposition response, evoked an increase in plasma adrenaline concentration also approximately matching the increase observed during the transposition response. It is concluded that the increase in plasma adrenaline secreted from the adrenal medulla is the main cause of the increase in hindquarter blood flow in the transposition response.
The effects of neomycin on membrane properties and discharge activity of an isolated sensory neuron
Authors: Nation Patrick N. , Roth Sheldon H.
Published: April 2011

The effects of neomycin sulfate were examined upon the discharge activity and electrical membrane properties of an isolated invertebrate sensory neuron, the crayfish stretch receptor neuron. Neomycin depressed cell discharge activity in a concentration-dependent manner over the concentration range of 0.01–1.0 mM. Significant concentration-related increases were observed in the resting membrane potential and the width of the orthodromic action potential. There was a significant concentration-dependent decrease in the fast rising phase of the antidromic action potential. Significant changes also were observed in other electrical properties such as membrane resistance, but these were found not to be concentration related. The most significant change was membrane hyperpolarization, which could account for the depression of cell discharge activity. The observed changes are consistent with a neomycin-induced change in the membrane potassium conductance. It is proposed that the neural effect of neomycin is a selective interaction with the neuronal membrane phospholipids.
Myosin light chain phosphorylation and contractile performance of human skeletal muscle
Authors: Stuart D. S. , Lingley M. D. , Grange R. W. , Houston M. E.
Published: April 2011

Twitch tension and maximal unloaded velocity of human knee extensor muscles were studied under conditions of low phosphate content of the phosphorylatable light chains (P-light chains) of myosin and elevated phosphate content, following a 10-s maximal voluntary isometric contraction (MVC). After the MVC, twitch tension was significantly potentiated, with greater potentiation observed at a shorter muscle length (p < 0.05). The MVC was associated with at least a twofold increase in phosphate content of the fast (LC2F) and two slow (LC2S and LC2S′) P-light chains, but this increase was unrelated to muscle length. No significant differences in knee extension velocity were observed between conditions where P-light chains had low or elevated phosphate content. Positive but nonsignificant correlations were noted between the extent of twitch potentiation and phosphate content of individual P-light chains as well as the percentage of type II muscle fibres in vastus lateralis muscle. No significant relationships were determined for myosin light chain kinase activity and either P-light chain phosphorylation or type II fibre percentage. These data suggest that, unlike other mammalian fast muscles, P-light chain phosphorylation of mixed human muscles is not strongly associated with altered contractile performance.
Degradation and conversion of somatostatin in normal and diabetic rats in vivo and in vitro
Authors: Seno Michiyo , Tsuda Kinsuke , Kitano Norikazu , Takeda Jun , Fukumoto Hirofumi , Koh Gyohan , Imura Hiroo , Taminato Tomohiko , Seino Yutaka
Published: April 2011

Plasma somatostatin-like immunoreactivity in the portal and jugular veins of streptozotocin diabetic rats was compared with that in normal control rats. In the diabetic group, somatostatin levels in the portal (p < 0.05) and jugular (p < 0.01) veins were both elevated compared with those in the control group. Moreover, the degree of elevation was greater in the jugular vein than in the portal vein. To further investigate the role of the liver in the clearance of somatostatin-28 in vivo, 2 μg of somatostatin-28 was administered as a bolus into the external jugular vein of intact and functionally hepatectomized rats. The mean half-time of somatostatin-28 was significantly longer in intact diabetic rats than in controls (p < 0.05). The functional hepatectomy did not cause a significant difference in the half-time in diabetic rats but made it longer in control rats. These results suggest that the longer half-time of somatostatin-28 in diabetic rats in vivo is due to its slower hepatic clearance. The hepatic clearance of somatostatin-28 and somatostatin-14 was further studied in vitro using a recirculating liver perfusion method. The hepatic clearance of 1.2 nM of either somatostatin-28 or somatostatin-14 was significantly lower in diabetic rats than in controls (p < 0.01). This indicates that elevated plasma somatostatin levels in diabetic rats are caused at least in part by decreased hepatic clearance of somatostatin. Gel chromatography of plasma samples obtained 0.5 and 4 min after the somatostatin-28 injection into intact, hepatectomized, and nephrectomized rats showed two major peaks: one compatible with somatostatin-28 and the other compatible with somatostatin-14 in elution position, in both diabetic and control rats. When somatostatin-28 was added to perfusate in vitro, however, gel chromatography failed to demonstrate the second peak was compatible with somatostatin-14 even after 30 min of recirculating perfusion. Gel chromatography of plasma samples obtained 5 and 30 min after incubation of somatostatin-28 showed two major peaks: one compatible with somatostatin-28 and the other compatible with somatostatin-14 in both diabetic and control rats. These results suggest that the conversion of somatostatin-28 to somatostatin-14 occurs mainly in plasma in vivo.
Euvolemic cirrhotic dogs in sodium balance maintain normal systemic hemodynamics
Authors: Levy M. , Maher Elizabeth , Wexler Marvin J.
Published: April 2011

Dogs with chronic biliary cirrhosis and portal hypertension commonly develop plasma volume expansion, urinary sodium retention, ascites, and perturbed systemic hemodynamics, i. e., a rise in cardiac output and a fall in peripheral vascular resistance. Our laboratory has previously demonstrated that creating a side-side portacaval anastomosis in such animals, and so venting hepatoportal pressure, will prevent sodium retention and ascites formation and will maintain the animals euvolemic. In the present study, in four cirrhotic dogs with such an anastomosis, observations made at 12 weeks postbiliary duct ligation, and in the presence of grossly disturbed liver function and morphology, failed to demonstrate any change from control conditions in arterial blood pressure, cardiac output, or peripheral vascular resistance. We conclude that venting hepatoportal pressure in cirrhotic dogs with markedly disturbed liver function prevents the advent of a hyperdynamic circulation, possibly by preventing volume expansion.
Bioactive atrial natriuretic factor-like peptides in rat anterior pituitary
Authors: Gutkowska Jolanta , Cantin Marc
Published: April 2011

The presence of biologically active atrial natriuretic factor (ANF)-like peptides was demonstrated in rat anterior pituitary. ANF-like immunoreactivity was detected in rat anterior pituitary by specific radioimmunoassay and was extracted from rat anterior pituitary homogenates by heat-activated Vycor glass beads; extracts were purified by reverse-phase high performance liquid chromatography. Two peaks containing ANF immunoreactive material were obtained. The first peak was eluted from the C18 μBondapak column at a position similar to the 28-amino acid carboxy terminal peptide (Ser99-Tyr126)-ANF of prohormone. The second peak had the same pattern of elution as the 126-amino acid prohormone, (Asn1-Tyr126)-ANF. The biological activity of the smaller molecular weight peptide (28 amino acid) was assessed by its inhibitory effect on 10−8 M ACTH-stimulated aldosterone secretion in rat zona glomeralosa cell suspension. This ANF-like material also displaced I125-labelled ANF from rat glomerular receptors with a potency similar to synthetic (Arg101-Tyr126)-ANF. Immunocytochemical localization revealed a distribution of ANF-stained cells similar in pattern and location to that of gonadotrophs. These results suggest the existence of biologically active ANF-like peptides and ANF prohormone within the anterior pituitary. However, their role remains to be elucidated.
Bay K 8644-like contractile effects of a peptide isolated from spontaneously hypertensive rats
Authors: Huang Bing S. , McCumbee William D. , Wright Gary L.
Published: April 2011

The in vitro contractile effect of a peptide recently isolated from the blood of spontaneously hypertensive rats was assessed on rat aortic rings. Preincubation of aortic rings with the peptide had no effect on resting tension but significantly enhanced K+ or norepinephrine-induced contractile responses. Contractile effects were abolished by removal of extracellular calcium or by additions of the calcium channel antagonists, verapamil and nifedipine. The antagonism of peptide enhancement of contraction by verapamil was noncompetitive, whereas nifedipine blockade was competitive in nature. Moreover, preincubation of aortic rings with the peptide attenuated the contractile response to Bay K 8644, a newly described synthetic calcium channel agonist. We suggest that this peptide has similar effects to Bay K 8644 and may act as an endogenous modulator of voltage-dependent calcium channels.
Neural control of canine colon motor function: studies in vivo
Authors: Gonda T. , Daniel E. E. , Kostolanska F. , Oki M. , Fox J. E. T.
Published: April 2011

The responses of the circular muscle of canine colon to stimulation of intrinsic nerves and to the probable mediators of these nerves were studied in vivo. In vivo studies were carried out using close intra-arterial injections and local field stimulation of proximal, mid-, and distal colon while recording circumferential contractions. Our results suggest that acetylcholine is the major excitatory mediator, but another excitatory mediator could be released by high frequency field stimulation after atropine. Norepinephrine had mixed inhibitory and excitatory effects, but no evidence was obtained that it was released by field stimulation. Substance P had mainly excitatory effects partly by a mechanism involving nerves and partly by a direct effect on muscle; it in addition to norepinephrine deserves further evaluation as the mediator of noncholinergic excitation to high frequency field stimulation. There is no explanation of the inhibition it produced after initial excitation during field stimulation. Vasoactive intestinal peptide had inhibitory effects but these were incomplete and inconsistent. This may be related to our inability to demonstrate relaxation or inhibition to field stimulation after atropine. Further evaluation of the possible role of vasoactive intestinal peptide and other agents as nonadrenergic, noncholinergic inhibitory mediators is required.
Effects of 6-hydroxydopamine on oxidative phosphorylation of mitochondria from rat striatum, cortex, and liver
Authors: Thakar J. H. , Hassan M. N.
Published: April 2011

The catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) has been used to produce cardiac chemical sympathectomy as well as a model of parkinsonism. Several mechanisms have been proposed to explain its cytotoxicity, including the productions of quinones, hydrogen peroxide, and free radicals by autooxidation and the uncoupling of mitochondrial oxidative phosphorylation. We have observed that 6-OHDA at a concentration of 0.05 mM rapidly consumes oxygen from the mitochondrial incubation medium but does not affect oxidative phosphorylation in the mitochondria from rat striatum, cortex, and liver. At the higher concentration of 0.5 mM, 6-OHDA consumes all of the available oxygen from the incubation medium. Mitochondria exposed to this concentration of 6-OHDA show decreases in the respiratory control ratio and adenosine triphosphate synthesis as measured by the consumption ratio of ADP to oxygen. Thus, only the higher (0.5 mM) concentration of 6-OHDA, which produces anoxia in vitro, also causes mitochondrial damage.
Saccadic command signals in the superior colliculus: implications for sensorimotor transformations
Authors: Sparks David L.
Published: April 2011

Recent findings concerning the anatomical and functional organization of the deep division of the primate superior colliculus are summarized. These data are interpreted as supporting the hypothesis that the deeper layers of the superior colliculus are organized in motor, rather than sensory, coordinates. According to this hypothesis, a dynamic remapping of sensory signals is required for interfacing with the map of motor error space contained in the superior colliculus
The 1987 James A. F. Stevenson Memorial Lecture. The development of fetal behavioural patterns
Authors: Dawes G. S.
Published: April 2011

The development of fetal behaviour is reviewed. Fetal cutaneous and muscle sensory receptors are developed by the time movements are first seen. Human infants certainly respond to painful stimuli at 28 weeks. There is no clear evidence that prenatal "stress," e.g., maternal exposure to random noise and bright lights, impairs fetal development in the rat, on the contrary. Fetal diurnal rhythms appear in man and sheep before the development of sleep states; they are dependent on maternal corticosteroids, but the fetal mechanism is uncertain. With the development of sleep states (in late gestation in man and sheep, postnatally in the rat), the complex central control of behaviour is gradually established, but wakefulness is still of low incidence. The location of the sleep cycle generator is uncertain; the results of experimental lesions of the brainstem in fetal lambs appear incompatible with studies in adult rats and cats.
The 1987 Upjohn Award Lecture. The role of membrane transport in the control of glucose metabolism and its coupling to cellular function
Authors: Bihler Ivan
Published: April 2011

In muscle and some other tissues the membrane transport of glucose is normally rate limiting for glucose utilization. It is modulated by insulin, muscular contraction, availability of oxygen and alternative substrates, and many other factors. An increase in glucose transport is associated with interventions increasing the influx of Ca2+ or its release from internal stores, thus presumably raising cytoplasmic [Ca2+]. Recent results with isolated myocytes from adult rat hearts are shown to be consistent with this hypothesis, and supporting evidence was obtained with other cell types. In avian erythrocytes glucose transport was found to be modulated only by internal Ca2+ redistribution, as plasmalemmal fluxes were very slow. In isolated bovine adrenal chromaffin cells glucose transport was found to be increased in a Ca2+-dependent manner by insulin (resembling muscle) and by stimulators of catecholamine secretion. These features are essentially preserved during the morphologic changes these cells undergo when cultured. Thus, enhanced glucose transport is often coupled to increased energy production for contraction, secretion, growth, etc., and to some hormonal signals. Other factors, notably the oxidation of fatty acids, exert a suppressive influence; this negative feedback may account in part for the decreased peripheral response to insulin in diabetes. It is suggested that binding of Ca2+ to a regulatory site, perhaps involved in the translocation of glucose transporters to the plasma membrane, may be involved in these regulatory phenomena and may play a central role in coupling glucose transport to a variety of other cellular processes.
Effect of hormones on hydrolase activities and DNA synthesis in kidney of the developing mouse
Authors: Brière Normand
Published: April 2011

The postnatal development of brush border enzyme activities, namely maltase, trehalase, alkaline phosphatase, γ-glutamyltranspeptidase, and leucylnaphthylamidase, as well as the ontogenic profile of DNA synthesis has been determined in the mouse kidney. In addition, these parameters were evaluated following daily administration of hormones during 3 days to 8-day-old mice. Insulin or epidermal growth factor induced a 34% increase of maltase activity over that of 11-day-old controls. Trehalase activity was precociously and significantly augmented by cortisone alone or combined with thyroxine (p < 0.05), although thyroxine alone had no influence. Only epidermal growth factor had a significant effect on alkaline phosphatase activity. γ-Glutamyltranspeptidase activity was significantly decreased when insulin and thyroxine were given simultaneously, but was not modified by any of the hormones injected separately. The level of leucylnaphthylamidase activity was enhanced by 70% after cortisone injection, but it was significantly reduced by thyroxine injected in combination with insulin or cortisone. The incorporation of [3H]thymidine into DNA was increased by 107% after epidermal growth factor administration, but it was decreased by 33% after the cortisone treatment. In spite of this precocious reduction, the level of incorporation was still 2 times higher than that in adult mice. These results show that hormones act separately or in cooperation to accelerate or retard the maturation of the suckling mouse kidney.
Interaction of amiloride with α-adrenoreceptors: evidence from radioligand binding studies
Authors: Periyasamy S. M.
Published: April 2011

We investigated the effect of amiloride on α-adrenoreceptors (α1 and α2) using radioligand binding techniques. Amiloride inhibited [3H]yohimbine and [3H]prazosin binding to α2- and α1-adrenoreceptors, respectively, from various tissues in a concentration-dependent manner. Amiloride was approximately 9–12 times more potent in inhibiting [3H]yohimbine binding to α2-adrenoreceptors from rat tissues than from other mammalian tissues. However, it had almost the same potency in inhibiting [3H]prazosin binding to α1-adrenoreceptors from rat as well as other mammalian tissues. Further, in rat tissues, amiloride was approximately 10 times more potent in inhibiting [3H]yohimbine than [3H]prazosin binding. Amiloride inhibited [3H]yohimbine binding noncompetitively and [3H]prazosin binding competitively. The inhibition of [3H]yohimbine and [3H]prazosin binding by amiloride was reversible. Since amiloride has been shown to be an inhibitor of Na+–H+ exchanger protein, we believe that it regulates the α2-adrenoreceptors by binding to Na+–H+ exchanger protein. Triamterene, a compound similar to amiloride in regard to diuretic effect, had very little effect on [3H]yohimbine and [3H]prazosin binding to rat kidney membranes, suggesting that the α-adrenoreceptor antagonistic properties of amiloride are not related to its antikaliuretic effect. The results of the present study suggest that some of the pharmacological actions of amiloride (antihypertensive and diuretic effects) can be explained in part by its regulatory effect on both α1- and α2-adrenoreceptors.
Interaction of amiloride and hydrochlorothiazide with atrial natriuretic factor in the medullary collecting duct
Authors: Wilson Douglas R. , Honrath U. , Sonnenberg H.
Published: April 2011

Medullary collecting duct function was studied using the in vivo microcatheterization technique in three groups of rats receiving amiloride, hydrochlorothiazide, or both diuretics. In each group of animals, atrial natriuretic factor (ANF 99–126) was given in the second phase of the experiment. The combination of amiloride and hydrochlorothiazide resulted in a more marked natriuresis than either diuretic given as a single agent. Sodium reabsorption in the medullary collecting duct, as a fraction of the delivered load, was reduced from 64% (amiloride) and 69% (hydrochlorothiazide) to 29% (amiloride and hydrochlorothiazide). Atrial natriuretic factor reduced collecting duct sodium reabsorption when added to amiloride or hydrochlorothiazide to 23% and to 41%, respectively, but had no additional effect when given with amiloride and hydrochlorothiazide. Potassium excretion with amiloride and hydrochlorothiazide was intermediate between amiloride or hydrochlorothiazide given as single agents. With the diuretic combination, potassium transport showed no significant reabsorption or secretion along the medullary collecting duct, amiloride was associated with potassium reabsorption, and hydrochlorothiazide was associated with potassium secretion in the duct. The results confirm the importance of the medullary collecting duct as a site of diuretic action. The known additive effects of amiloride and hydrochlorothiazide on sodium excretion and the opposing effects of these agents on potassium excretion occur, to a major degree, in the medullary collecting duct. Furthermore, the additive effects of amiloride and ANF indicate that blocking of amiloride-sensitive sodium channels is not the only mechanism of action of ANF on duct salt transport in vivo.
Effects of sucralfate on gastric prostaglandin and leukotriene synthesis: relationship to protective actions
Authors: Wallace John L. , Morris Gerald P. , Beck Paul L. , Williamson Todd E. , Gingras Guy R.
Published: April 2011

The mechanism of the protective actions of sucralfate against ethanol-induced gastric mucosal damage in the rat has been investigated. In particular, the role of prostaglandins as mediators of such protection was assessed. Oral administration of sucralfate at a dose causing a significant reduction of ethanol-induced gastric damage (500 mg/kg) did not significantly alter gastric 6-ketoprostaglandin F1α synthesis. Pretreatment with indomethacin at a dose that inhibited gastric cyclooxygenase activity by an average of 88% did not affect the protective actions of sucralfate. To further investigate the mechanism of action of sucralfate, an ex vivo gastric chamber model was used in which sucralfate could be applied to only one side of the mucosa. Sucralfate did not affect gastric prostaglandin synthesis, but did cause a significant increase in leukotriene C4 synthesis, a fall in transmucosal potential difference, and a significant decrease in gastric myeloperoxidase activity on the side exposed to sucralfate. These observations suggest that sucralfate has an irritant action on the mucosa. The release of mediators in response to such irritation may play an important role in the protective action of sucralfate. The present study supports the hypothesis that prostaglandins do not mediate the protection afforded by exposure to sucralfate.
Effect of active head movements about the pitch, roll, and yaw axes on human optokinetic afternystagmus
Authors: Lafortune S. H. , Ireland D. J. , Jell R. M.
Published: April 2011

Effects of active head movements about the pitch, roll, or yaw axes on horizontal optokinetic afternystagmas (OKAN) were examined in 16 subjects to test the hypothesis that otolith organ mediated activity induced by a change in head position can couple to the horizontal velocity storage in humans. Active head movements about the pitch axis, forwards or backwards, produced significant OKAN suppression. Pitch forward head movements exerted the strongest effect. Active head movements about the roll axis towards the right also produced OKAN suppression but only if the tilted position was sustained. No suppression was observed following sustained yaw. However, an unsustained yaw left movement after rightward drum rotation significantly enhanced OKAN. Sustained head movement trials did not significantly alter subsequent control trials. In contrast, unsustained movements about the pitch axis, which involve more complex interactions, exerted long-term effects on subsequent control trials. We conclude that otolith organ mediated activity arising from pitch or roll head movements couples to the horizontal velocity storage in humans, thereby suppressing ongoing OKAN. Activity arising from the horizontal canals during an unsustained yaw movement (observed mainly with yaw left), following drum rotation in a direction contralateral to the movement, may also couple to the velocity storage, resulting in increased activity instead of suppression.
Manganese can inhibit or potentiate contractile responses in mesenteric portal vein
Authors: Sutter M. C. , May P. B. Y. , Lim S. L.
Published: April 2011

The effects of a number of agents believed to interfere with Ca were examined on contraction induced by noradrenaline (NA) or K in rat mesenteric portal veins. The organic calcium antagonists nifedipine, verapamil, methoxyverapamil, and felodipine slowly produced maximum inhibitory effects, nifedipine being fastest with a [Formula: see text] of 20 min. In contrast, the inhibitory effects of Mn were immediate but disappeared on continued exposure of the tissue to Mn. After removal of Mn from the bath fluid, an above normal contraction was produced by K or NA. Measurement of Mn by atomic absorption spectrometry showed that the concentrations of EDTA-resistant Mn increased in parallel with the loss of inhibitory effects of Mn. This is consistent with an external inhibitory effect of Mn but a potentiating effect of Mn once it reaches an EDTA-inaccessible site. The potentiating effect of Mn was not seen with other ions such as Cd, Ni, Co, Mg, and La, which produced only inhibition of responses to NA or K. Contractile responses to Ba were examined in the absence of external Ca and it was found that the responses decreased with time. The presence of Mn not only prevented the loss of contractility but produced a marked increase in the response to Ba. Relaxation rates were also studied and it was found that Mn speeds the relaxation of contractures produced by NA or Ba as long as Mn is present in the bath fluid, but Mn slows relaxation when it is present (presumably) intracellularly. Mn does not alter relaxation rates of K contractures. These results suggest that the limiting step in the magnitude of NA, Ba, or K contractures involves an intracellular site at which Mn acts, whereas the limiting step in the relaxation of NA or Ba contractures involves a relatively superficial site readily accessible to external Mn. This site is not involved in relaxation of K-induced contractures.
Small fibronectin fragments induce endothelium-dependent vascular relaxations
Authors: Laplante Claude , St-Pierre Serge , Beaulieu André D. , Marceau François
Published: April 2011

Strips of rabbit thoracic aorta precontracted with phenylephrine relaxed when exposed to selected synthetic peptides derived from the cell attachment domain of fibronectin. The relaxations elicited by both acetylcholine and the hexapeptide Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) were dependent on the presence of an intact endothelium, were resistant to indomethacin, and were inhibited by hemoglobin. The structure–activity relationship of four oligopeptides derived from fibronectin was in fair agreement with their ability to prevent fibronectin-mediated cell adhesion in other experimental systems. Human plasma fibronectin (up to 2.3 μM) did not relax this preparation and did not prevent the relaxant effect of the synthetic hexapeptide GRGDSP. On the rabbit isolated mesenteric artery, the relaxations induced by GRGDSP were significantly inhibited by indomethacin treatment, suggesting a contribution of locally produced prostaglandins. The displacement of fibronectin by soluble peptides from its binding sites on endothelial cells may result in significant pharmacologic responses, probably resulting from perturbations of the endothelial cell membranes.
Role of hyperthyroidism in increased thermogenesis in the cold-acclimated Syrian hamster
Authors: Sigurdson S. Lynn , Himms-Hagen Jean
Published: April 2011

The oxygen consumption of cold-acclimated Syrian hamsters (measured in pentobarbital-anaesthetized animals) was 59% greater than that of warm-acclimated hamsters. Upon return of the cold-acclimated hamsters to 24 °C, the elevated metabolic rate declined slowly, with half-life of approximately 1 day. The increase correlated well with our previous finding of a four-fold increase in serum 3,5,3′-triiodothyronine concentration in cold-acclimated hamsters and the slow decline in concentration of this hormone during deacclimation. Daily administration of T3 (for 7 days) to warm-acclimated hamsters at 24 °C resulted in a similar increase in oxygen consumption that persisted 1 day after the last injection and had disappeared by 7 days after the last injection. We conclude that the high concentration of serum triiodothyronine in the cold-acclimated hamster exerts a thermogenic effect that probably contributes to thermoregulatory thermogenesis in the cold.
Autoregulation of blood flow in renal medulla of the rat: no role for angiotensin II
Authors: Cupples W. A. , Marsh D. J.
Published: April 2011

Autoregulation of blood flow was assessed by a dual-slit technique in descending and ascending vasa recta of the exposed renal papillae of antidiuretic rats. There was complete autoregulation of blood flow in descending vasa recta. The lower limit of autoregulation was approximately 85 mmHg (1 mmHg = 133.3 Pa) and the upper limit was greater then 160 mmHg. Auto-regulation in ascending vasa recta was also good. To test the role of angiotensin II in this autoregulation, the converting enzyme inhibitor captopril was infused. Captopril had no effect on autoregulation of blood flow in either descending or ascending vasa recta. We conclude that blood flow in vasa recta of renal medulla is efficiently autoregulated and that this autoregulation is independent of angiotensin II
The effect of lung concentrations of glutathione and vitamin E on the pulmonary toxicity of 3-methylindole
Authors: Kubow Stan , Bray Tammy M.
Published: April 2011

The relative roles of tissue glutathione and vitamin E concentrations in the pneumotoxicity of 3-methylindole were studied. Thirty-two goats were divided into four groups and pretreated with (i) vitamin E + cysteine, (ii) vitamin E + diethylmaleate, (iii) cysteine, and (iv) diethylmaleate to vary tissue concentrations of glutathione and (or) vitamin E. Lung tissue concentrations of glutathione, vitamin E, and cytochrome P-450 were measured after pretreatments in four of eight animals in each group. Groups pretreated with cysteine had higher glutathione levels in the lung than those of diethylmaleate-pretreated goats. Goats receiving vitamin E had significantly higher concentrations of vitamin E than unsupplemented groups. After pretreatments the other four goats in each group were challenged with 3-methylindole (0.03 g/kg body weight) by intrajugular infusion. The severity of lung lesions was evaluated and scored by gross and microscopic examination at 72 h after infusion. 3-Methylindole-induced lung lesions were severe when tissue glutathione was reduced and were mild when tissue glutathione was induced. Enhancement of tissue vitamin E did not significantly affect 3-methylindole toxicity. These results indicate that the initial toxicological event is likely to be the result of binding of 3-methylindole free radical covalently to cellular protein rather than lipid peroxidation.
Systolic pressure gradients between the wall of the left ventricle, the left ventricular chamber, and the aorta during positive inotropic states: implications for left ventricular efficiency
Authors: Butler C. K. , Wong A. Y. K. , Armour J. A.
Published: April 2011

To study systolic pressure gradients developed between the left ventricular wall, its chamber, and the aortic root, in one group of dogs left ventricle ventral wall intramyocardial pressure, left ventricular outflow tract pressure, and aorta pressure were compared with aortic flow as well as left ventricular dimension changes during control conditions as well as during positive intropic states induced by isoproterenol, stellate ganglion stimulation, and noradrenaline. In another group of dogs systolic pressures in the ventral wall of the left ventricle, the main portion of the left ventricular chamber, and the aorta were compared with aortic flow during similar interventions, before and after the administration of phentolamine. Pressure gradients between the wall of the left ventricle and the outflow tract of the left ventricle were minimal during control states, but during the three positive inotropic states were increased significantly. In contrast, pressure gradients between the outflow tract of the left ventricle and the aortic root were insignificant during positive inotropic states; those between the wall and main portion of the chamber were only significantly different during left stellate ganglion stimulation. The data derived from these experiments indicate that useful peak power output of the left ventricle (systolic aortic pressure × flow) is unchanged following isoproterenol infusion, but is increased by stellate ganglion stimulation and noradrenaline. The useful peak power output index (an index of left ventricular efficiency derived by dividing useful peak power output by peak intramyocardial pressure) was reduced more by isoproterenol than the other two interventions. It is concluded that the product of aortic flow and pressure does not accurately indicate the efficiency of the heart during hyperdynamic states. Second, a derived momentum equation indicates that the relatively large pressure gradients which develop between the main chamber of the left ventricle and the aortic root during positive inotropic states are due primarily to fluid dynamic changes and internal dimension changes within the chamber.
The kinetics of drug–membrane interactions in human erythrocytes from neonates
Authors: Eskelinen Sinikka
Published: April 2011

The kinetics of drug–membrane interactions of erythrocytes from neonates were compared with those from adults by monitoring the time course of the shape transformations and vesicle release caused by drugs, using a light microscope – video recording technique. Both crenation caused by lysophosphatidylcholine (LPC) and cupping caused by chlorpromazine (CPZ) took place more slowly in the neonatal cells than in the cells from adults. The equilibrium concentrations of LPC and CPZ in erythrocytes did not differ significantly between the neonates and adults, however. The slower responses of the neonatal erythrocytes can be explained by the presence of negatively charged phosphatidylethanolamine and phosphatidylserine in the outer layer of the erythrocyte membrane, which may reduce the rate of incorporation of amphipathic LPC and attract cationic CPZ to remain in the outer membrane layer, lowering the rate of inward bending of the membrane normally caused by CPZ.
The Anrep effect: an intrinsic myocardial mechanism
Authors: Nichols C. G. , Hanck D. A. , Jewell B. R.
Published: April 2011

In cat papillary muscles contracting physiologically, increasing the afterload caused a biphasic change in contractility. In response to an increase in afterload, contractility (as measured by peak shortening, peak developed force, or peak dF/dt) initially decreased (antihomeometric autoregulation) over the first few beats and then increased slowly with t1/2 of about 3 min at 30 °C and about 1 min at 37 °C (homeometric autoregulation). The antihomeometric autoregulation is due to decreased active shortening when the afterload is increased, since it also occurs in response to increased afterload in isotonic contractions. The secondary slow increase in contractility is primarily due to the increase in mean diastolic length that occurs as a result of increased afterload. The time course and the magnitude of the biphasic change in contractility are very similar to those observed in response to afterload increase in intact hearts; we suggest that the secondary slow increase in contractility that we observed is a contributory mechanism to homeometric autoregulation (or the Anrep effect), as it is observed in the whole heart.
Adenosine modulation of vasoconstrictor responses to stimulation of sympathetic nerves and norepinephrine infusion in the superior mesenteric artery of the cat
Authors: Lautt W. Wayne , Lockhart Leslie K. , Legare Dallas J.
Published: April 2011

Vasoconstriction induced by sympathetic nerve stimulation and by norepinephrine infusion in the superior mesenteric artery of cats anesthetized with pentobarbital was inhibited by adenosine infusions in a dose-related way. The responses to nerve stimulation were not inhibited to a greater extent than the responses to norepinephrine, thus suggesting no presynaptic modulation of sympathetic nerves supplying the resistance vessels of the feline intestinal vascular bed. Blockade of adenosine receptors using 8-phenyltheophylline did not alter the degree of constriction induced by nerve stimulation or norepinephrine infusion, indicating that in the fasted cat, endogenous adenosine co-released or released subsequent to constriction does not affect the peak vasoconstriction reached. Isoproterenol caused similar degrees of vasodilation as adenosine but did not show significant antagonism of the pooled responses to nerve stimulation or norepinephrine infusion; there was no tendency for the degree of dilation induced by isoproterenol to correlate with the inhibition of constrictor responses. Thus, the effect of adenosine on nerve- and norepinephrine-induced constriction is not secondary to nonspecific vasodilation.
The effects of amino acid loading on glomerular filtration in dogs on different protein diets: a controlled study
Authors: Fine A.
Published: April 2011

Considerable variation in both the magnitude and pattern of response of glomerular filtration rate (GFR) to protein loading in omnivores has been reported in the literature. These experiments were designed to examine, under carefully controlled conditions, the effects of different acute protein loads given to a group of dogs placed on a normal protein (NP) intake for 4 weeks and to the same dogs when on a low protein (LP) intake for the same duration. GFR did not change when the dogs were changed from NP to LP diets, 3.0 + 0.2 (NP) vs. 3.2 + 0.3 (LP) mL∙min−1∙kg−1. Intravenous amino acid was infused at 15, 25, and 40 mL/h on different days. Regardless of whether on a low or high protein diet, the GFR did not change. Another set of experiments was performed in another Canadian centre 2000 miles away. In these studies with dogs on a similar normal protein diet, a striking rise in GFR occurred following amino-acid infusion at 25 mL/h, 3.1 + 0.3 vs. 4.8 + 0.6 mL∙min−1∙kg−1 (p < 0.001). These results demonstrate, at least in the dog, that contrary to previous reports, dietary protein changes do not affect the GFR. Furthermore, the GFR response to an acute intravenous protein load does not depend on the amount of protein given nor the previous protein diet but appears to be possibly dependent on other factors that may be environmental or congenital.
Effects of physostigmine and scopolamine on long-term potentiation of hippocampal population spikes in rats
Authors: Ito Tsugutaka , Miura Yoshiki , Kadokawa Toshiaki
Published: April 2011

To elucidate an involvement of the cholinergic system in the long-term potentiation phenomenon, effects of physostigmine and scopolamine on population spike and its long-term potentiation in the dentate granule cell layer of anesthetized rats and in the CA1 pyramidal cell layer of rat hippocampal slices were examined. In anesthetized rats, physostigmine (0.01 mg/kg, i.v.) enhanced at a late phase the long-term potentiation induced by tetanic stimulation (15 Hz, 15 s, 7.5 times the threshold for population spike) of the perforant path, while scopolamine (1.0 mg/kg) suppressed it at an early phase. The two drugs did not affect the population spike itself. The time course of the long-term potentiation under the treatment of physostigmine was similar to that induced by stronger tetanic stimulation (10 times the threshold). In hippocampal slices, physostigmine (10−6 M) showed a tendency to enhance the long-term potentiation induced by tetanic stimulation (15 Hz, 15 s, 5 times the threshold) of the stratum radiatum, with an increase of the population spike itself. Scopolamine (10−5 M) markedly suppressed the long-term potentiation with a decrease of the population spike itself. From these results, it is suggested that cholinergic modification by physostigmine or scopolamine affects the long-term potentiation phenomenon in the hippocampus under the in vivo and in vitro conditions.