bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin resistance and its reversal by in vivo infusion of ATP in hemorrhagic shock
Authors: Chaudry Irshad H. , Sayeed Mohammed M. , Baue Arthur E.
Published: April 2011

Hemorrhagic shock in rats was produced by bleeding the animals to a mean arterial pressure of 40 mmHg, which was maintained for 2 h. Muscles from these animals ('shock' muscles) demonstrated basal glucose uptake values unchanged from control values but, unlike the control muscles, the 'shock' muscles showed resistance to the stimulation of glucose uptake by insulin. Infusion of ATP–MgCl2, ADP–MgCl2, adenosine–MgCl2, or GTP–MgCl2 to animals following shock had no effect on basal glucose uptake; however, ATP–MgCl2 but not the other nucleotides permitted insulin to exert its stimulatory effect on such muscles. An optimal insulin effect in ATP–MgCl2 treated 'shock' muscles occurred at an insulin concentration of 0.001 U/ml, which is also the concentration required to produce optimal insulin effect in control muscles. Following 1-h incubation in Krebs–HCO3 medium, intracellular ATP contents of 'shock' muscles were about 50% lower than in control muscles. Treatment with ATP–MgCl2 following shock, however, resulted in ATP contents in such muscles similar to those in control muscles. Possible mechanisms for this reversal of insulin resistance by in vivo infusion of ATP–MgCl2 in shock are discussed.
Cardiac edema in dogs: Distribution of renal blood flow and glomerular filtrate
Authors: Boudreau Robert J. , Mandin Henry
Published: April 2011

The injection of Freund's adjuvant into the pericardial sac of 29 dogs resulted in chronic pericardial tamponade with persistent sodium retention. Micropuncture, clearance, and radioactive microsphere experiments were initiated 6–13 days after pericardial injection and 60 min after pericardiocentesis. Pericardiocentesis increased sodium excretion (from 12.2 to 41.3 μequiv./min) and mean arterial pressure (+ 20 mmHg (1 mmHg = 133.322 Pa)). Central venous pressure decreased 6.5 mmHg, as did hematocrit (from 45.7 to 39.8%) and plasma protein concentration (from 5.88 to 5.15 g%). Pericardiocentesis had no significant effect on renal blood flow (RBF), nor plasma flow. Redistribution of glomerular filtrate was suggested by the observation that superficial nephron glomerular filtration rate increased (from 91 to 108 nL/min) while glomerular filtration rate remained unaltered. Determination of intrarenal distribution of RBF revealed that cortical blood flow also distributed superficially. A significant increase in the fraction of RBF perfusing zone 1 (outer cortex) and a decrease in fractional perfusion of zones 2, 3, and 4 (juxtamedullary cortex) were observed in each experiment following pericardiocentesis. RBF distribution examined in a series of six animals prior to and during the development of pericardial tamponade showed the opposite effect.These results indicate that pericardiocentesis causes redistribution of both glomerular filtrate and RBF to superficial nephrons. The development of pericardial tamponade was associated with increased fractional juxtamedullary blood flow. These changes may have been the result of altered blood pressure, hematocrit, plasma protein concentration, or altered renal resistance.
The effect of vasoactive intestinal polypeptide on the urinary bladder and taenia coli of the guinea pig
Authors: Johns A.
Published: April 2011

The effect of vasoactive intestinal polypeptide (VIP) on the contractile activity of the urinary bladder and taenia coli of the guinea pig has been investigated. In the urinary bladder VIP caused a weak contraction and a small potentiation of the nerve-induced contraction. In the taenia coli VIP caused a small relaxation and had no effect on the nerve-induced relaxation of the preparation. The present experiments provide no evidence that VIP fulfills a role as a neurotransmitter in the urinary bladder or taenia coli, but it could be a modulator of transmitter action in the urinary bladder.
Sensitivity of hypothalamic sites to salicylate and prostaglandin
Authors: Vaughn L. K. , Veale W. L. , Cooper K. E.
Published: April 2011

This study was designed to determine the dose of salicylate necessary to produce substantial antipyresis, and to determine the relationship between the response to salicylate and prostaglandin infused into the same region of the preoptic area of the rabbit. The effect of preoptic infusions of three doses of sodium salicylate, or a control solution, on the fever produced by an intravenous injection of endogenous pyrogen was measured. The pyrogenic response to prostaglandin E1 injected into the same preoptic sites in the same rabbits was also monitored. The results showed that the 50 μg/μL per hour dose of salicylate did not produce significant antipyresis but that the 100 and 200 μg/μL per hour doses did. The results also showed a significant correlation between the magnitude of fever produced by prostaglandin E1 and the magnitude of antipyresis produced by sodium salicylate at a particular site. Those sites at which infusion of salicylate produced the most effective antipyresis were also the ones at which prostaglandin E1 produced the largest fevers.
Effects of 16,16-dimethyl prostaglandin E2 on bile-induced histamine release and permeability alterations in canine oxyntic mucosa
Authors: Tepperman B. L.
Published: April 2011

Damage to the stomach results in excessive movement of hydrogen ion (H+) out of the lumen, and increased movement of sodium (Na+) and potassium (K+) into the lumen. Histamine liberation during damage probably adds to the destruction by increased capillary permeability and formation of edema. Previous reports have shown that the synthetic prostaglandin analogue 16,16-dimethyl prostaglandin E2 (dm PGE2) protects dog gastric mucosa from aspirin- and ethanol-induced gastric mucosal damage. The effects of dm PGE2 on bile salt (sodium taurocholate) induced injury has not been investigated. Using the canine Heidenhain pouch, the present study examined the action of dm PGE2 on gastric mucosal damage induced by 5 mM sodium taurocholate in 100 mM HCl. Bile salt damaged the pouch mucosa as evidenced by an increased loss of H+, and increased net fluxes of both Na+ and K+. There was also an increase in the histamine content of the fluid irrigating the Heidenhain pouch. Intravenous injection of dm PGE2 in the doses 0.1 and 1.0 μg/kg [Formula: see text] before administration of the sodium taurocholate in HCl significantly reduced the net loss of H+ and the gain of Na+, K+ and histamine. It is concluded the dm PGE2 effectively protects the canine gastric mucosa from the damaging effects of bile salt and that the mechanism of dm PGE2 protection of canine oxyntic mucosa may be mediated in part via inhibition of the gastric mucosal release of histamine.
The ultrastructure of blebs induced in the hamster jejunum by ethanol
Authors: Fox J. E. , Morris G. P. , Beck I. T. , McElligott T. F.
Published: April 2011

Previous light microscopic studies showed that perfusion of the hamster jejunum with 4.8% ethanol (ethanol period) in vivo produced fluid-filled subepithelial blisters (blebs) on the villi. These blebs had virtually disappeared within 45 min after the discontinuation of the ethanol perfusion (recovery period). The present study examined these ethanol-induced changes in the jejunum by scanning (SEM) and transmission (TEM) electron microscopy. TEM revealed that ethanol did not damage epithelial cells in areas where blebs were not present. In these areas the basal surfaces of the epithelial cells were attached to the basal lamina, and the lateral intercellular spaces (LIS) were open. In the areas where blebs formed, the stretched epithelial cells which covered the blebs lost their basal anchoring and so could not maintain their LIS. Both SEM and TEM indicate that there was a decrease in the quantity of glycocalyx at the surfaces of cells which covered blebs. Our findings indicate that ethanol does not directly damage epithelial ceils but that the cellular damage is due to detachment over the blebs. It is likely that ethanol at first traverses the epithelial layer and then produces stasis in the villus core. Continued fluid transport by the epithelial layer in the presence of statis results in accumulation of the fluid and widely dilated LIS. With subsequent enlargement of the LIS the bases of the cells detach from the basal lamina and blebs are formed.
Carotid sinus reflex and norepinephrine release following acute volume depletion in dogs
Authors: Carrière Serge , Cardinal Jean , LeGrimellec Christian
Published: April 2011

Norepinephrine (NE) release and pressor response to sympathetic stimulation were studied in dogs under furosemide-induced acute volume depletion. The rise in blood pressure observed following carotid clamping proved similar before and after acute salt and water depletion in the first group of animals and NE rose comparably in these two conditions. Similar results were obtained in a second group of dogs that received an angiotensin II converting enzyme inhibitor (CEI). This study shows that contrary to isotonic saline loading, acute salt and water depletion cause a progressive increase in NE plasma levels. Moreover, these results clearly demonstrate that the decrease in sympatho–adrenergic response and the predominant role played by the rennin–angiotensin system during chronic salt depletion are not observed in acute conditions.
Antagonists of angiotensin II containing N-methyl-L-alanine and DL-nipecotic acid in position 7
Authors: Moore Graham J. , Ko Evelyn M.
Published: April 2011

[1-sarcosine, 7-N-methyl-L-alanine, 8-isoleucine]-Angiotensin II and [1-sarcosine, 7-DL-nipecotic acid, 8-isoleucine]-angiotensin II were synthesized by the solid-phase method and purified by cation-exchange chromatography and high-pressure liquid chromatography. In the isolated rat uterus these analogs and < 0.1% of the myotropic activity of angiotensin II and inhibited angiotensin II with pA2 values of 8.2 and 7.8, respectively. In the rat pressor assay (vagotomized ganglion blocked rat) these analogs had 0.9 and 2.8%, respectively, of the pressor activity of angiotensin II. The results show that the proline residue in position 7 of [Sar1,Ile8]-angiotensin II may be replaced by other secondary amino acids without disrupting interactions at angiotensin II receptors.
A source of large axons for neurophysiology: The North Atlantic squid Illex illecebrosus
Authors: Geduldig D. , Hoekman T.
Published: April 2011

A new axon preparation from the ommastrephid squid (Illex illecebrosus (Lesueur)) is described. This squid is common in the Northwestern Atlantic and features a number of long, unbranched, and moderately large-diameter axons having no apparent 'twigging.' Although the diameters of these axons are somewhat smaller than those of 'giant' axons coming from some other species of squid, this axon preparation should be considered as an attractive alternative for neurobiologic research.
Actions of the novel bronchodilator, trimetaquinol, on bovine pulmonary vein
Authors: Hanna Christopher J. , Hambleton Ann , Eyre Peter
Published: April 2011

The actions of the β-sympathomimetic bronchodilator trimetaquinol (TMQ) were examined on bovine pulmonary vein smooth muscle in vitro. TMQ partially and reversibly inhibited 5-hydroxytryptamine (5HT) induced contractions of the vein strips. The relaxant activity was neither blocked by propranolol (10−7 M) nor enhanced by phentolamine (10−7 M). Isoproterenol, alone or in the presence of phentolamine (10−7 M), was much less effective than TMQ in relaxing 5HT-induced contractions. From these results it is suggested that TMQ functions via a "non-β-adrenergic" mechanism to relax bovine pulmonary vein smooth muscle.
The innervation of smooth muscle in the primary bronchus of the chicken
Authors: Bhatla R. , Ferguson C. C. , Richardson J. B.
Published: April 2011

The innervation of the primary bronchus of the chicken was studied with in vitro pharmacological techniques and with the electron microscope. The primary response of the smooth muscle to field stimulation is relaxation of the muscle and this is not blocked by adrenergic blocking agents. Excitatory cholinergic innervation can be demonstrated when the muscle is partially relaxed. Examination of the ultrastructure of the muscle and nerves shows numerous axon profiles filled with large granular vesicles of the type associated with noradrenergic or purinergic neurotransmission. Agranular vesicles characteristic of cholinergic innervation are also seen but there is no evidence of adrenergic innervation to the smooth muscle. The smooth muscle ceils show connections of the nexus type. These findings indicate that the primary bronchus of the chicken has a dominant inhibitory system and this is nonadrenergic in type.
The effects of hemicholinium-3 on synaptic depression, facilitation, and post-tetanic potentiation at an identified synapse of Aplysia californica
Authors: Tremblay Jacques P. , Grenon Gilles , Plourde Gilles
Published: April 2011

(1) Hemicholinium-3 (HC-3) reduces the size of the depolarization obtained by iontophoretic application of acetylcholine (ACh) on cell R15 in Aplysia. This effect of HC-3 is not antagonized by choline and is attributed to a blockade of the postsynaptic cholinergic excitatory receptor as HC-3 has no effect on the membrane potential and resistance of R15.(2) HC-3 does not affect the desensitization observed by giving successive pulses of exogenous ACh.(3) HC-3 reduces the cholinergic excitatory postsynaptic potentials (EPSPs) recorded in cell R15 following stimulation of the right connective (synapse RC1-R15). This effect cannot be accounted for solely by the postsynaptic action of HC-3, as this effect is partially antagonized by choline and is increased by a higher stimulation frequency of the synapse or by a higher extracellular Ca2+ concentration.(4) Part of the action of HC-3 on the EPSP size is therefore accounted for by a reduction of choline reuptake by the presynaptic terminal. This would reduce the size of the storage pool of neurotransmitter and indirectly the size of the available pool of neurotransmitter.(5) Synapse RC1-R15 was stimulated for a long period (30 min) at 2 Hz with or without HC-3 in the perfusate. Following this initial phase, the rate of transmitter mobilization was evaluated by giving a short train of 100 stimuli at several frequencies. In the presence of HC-3, the rate of mobilization is reduced more at the higher frequencies. As the depletion of the storage pool produced by HC-3 during the initial phase is the same in all cases, it is concluded that the process of mobilization is more sensitive to a reduction of the storage pool when the mobilization rate is higher.(6) HC-3 increases the posttetanic potentiation (PTP) and the synaptic depression observed at synapse RC1-R15 when perfused in the presence of elevated extracellular Ca2+ (2 × Ca2+, 22 mM), but HC-3 reduces the amplitudes of these phenomena when perfused in reduced Ca2+ (½ × Ca2+, 5.5 mM).(7) HC-3 has been perfused alone or with choline, with or without continuous stimulation at 2 Hz in a medium containing a high concentration of Ca2±. Following this initial phase, PTP and depression were tested by a short train of stimulation. When there is stimulation during the initial phase, choline significantly antagonizes the increase of PTP and depression produced by HC-3 alone. However, when there is no stimulation during the initial phase, choline increases the augmentation of PTP and depression produced by HC-3 alone.(8) Similar experiments were also done in low Ca2± concentration. With stimulation during the initial phase, choline does not antagonize the reduction of PTP and depression produced by HC-3. However, without stimulation during the initial phase, choline significantly antagonizes the reduction of PTP and depression produced by HC-3.
Age-related differences in the febrile response of the New Zealand White rabbit to endotoxin
Authors: Ferguson A. V. , Veale W. L. , Cooper K. E.
Published: April 2011

The effect of age on the febrile response of New Zealand White rabbits was investigated by administering bacterial endotoxin intravenously to animals from two different age groups. Rabbits greater than 2.0 years of age developed significantly smaller fevers than did animals that were less than 1.0 year old (p < 0.001). The deficit in the febrile response of older animals was specifically related to an absence of the second peak of fever.
Patterns of muscular and motor cortical activity during a simple arm movement in the monkey
Authors: Lamarre Y. , Spidalieri G. , Lund J. P.
Published: April 2011

This article describes the behavior of motor cortex neurons recorded in macaque monkeys (Macaca mulatta) which had been trained to make extension and flexion movements about the elbow in response to auditory, visual, or somesthetic cues. The pattern of activity of 65% of those movement-related neurons which were recorded during both flexion and extension was reciprocally related to the direction of movement. However, the movements of extension and flexion were made by co-contraction of the biceps and triceps in a pattern that did not match that of the motor cortex neurons. The majority of motor cortex neurons had firing frequencies that were related to movement parameters but by their nature could not be directly involved in the control of α motoneurons in both directions of movement. We suggest that they could, instead, control the fusimotor system. It is more likely that α motoneurons are controlled by the 35% of motor cortex neurons that, like the muscles, do not show reciprocal patterns of activity for movements in opposite directions.
Influence of vitamin D3 states, phenobarbital, and diphenylhydantoin treatment on the plasma 25-hydroxyvitamin D3 concentrations in the rat
Authors: Gascon-Barré Marielle , Delvin Edgard E. , Glorieux Francis H. , Côté Michel G.
Published: April 2011

The plasma 25-hydroxyvitamin D3 (25(OH)D3) response to a single intraportal injection of 100 μg∙kg−1 of vitamin D3 (D3) was determined before as well as 24 and 48 h after D3 administration in male Sprague-Dawley rats following a 3-week treatment with phenobarbital (PB), diphenylhydantoin (DPH), or the combination of the two drugs during normal vitamin D status (D+) or vitamin D deficiency (D−). Before D3 injection, plasma 25(OH)D3 concentrations were not statistically affected by the anticonvulsant (ACV) drug treatment in the D+ group and were at undetectable levels in the D− group. Twenty-four hours after D3, mean plasma 25(OH)D3 concentrations in the D− rats varied between 24.4 and 76.7 ng∙mL−1 while, in the D+ animals, the mean concentrats varied between 28.3 and 50.1 ng∙mL−1. The factorial analysis of variance revealed a significant effect of the drug treatment on plasma 25(OH)D3, concentrations in all groups (p < 0.005), a nonsignificant effect of the deficiency but a statistically significant positive interaction between PB and the D− state (p < 0.001). In the subsequent 24 h, 25(OH)D3 concentrations did not change significantly in both D− and D+ controls; in ACV drug treated animals, the plasma 25(OH)D3 concentrations dropped in D− animals only, revealing a statistically significant effect of the deficiency on plasma 25(OH)D3 (p < 0.001). These observations suggest that (1) during constant intake of D3, plasma 25(OH)D3 concentrations are not affected by ACV drug treatment; (2) 24 h after an acute D3 load, the plasma 25(OH)D3 concentrations attained are (a) independent of D3 nutritional status, (b) stimulated by ACV drug treatment both in the D+ and D− states, and (c) potentiated by PB treatment during D deficiency; (3) 48 h after D3 administration, ACV drug treatment contributes, in the D− state, to accelerate the plasma 25(OH)D3 disappearance; and (4) the effects of PB on plasma 25(OH)D3 concentrations are more pronounced than those of DPH and not potentiated by the combined drug treatment.
Somatostatin Inhibits prolactin secretion in the estradiol primed male rat
Authors: Cooper G. R. , Shin S. H.
Published: April 2011

Somatostatin inhibits not only growth hormone secretion, but also the secretion of several other hormones. The role of somatostatin in prolactin (PRL) secretion has not been clearly demonstrated. The present study was undertaken to examine the effects of somatostatin on rat PRL secretion in several different circumstances where the circulating PRL level is elevated: (1) the estradiol primed intact male rat, (2) normal and (3) estradiol primed rats pretreated with pimozide, (4) normal and (5) estradiol primed hypophysectomized male rats with adenohypophyses grafted under the kidney capsule (HAG rat). Blood samples (70 μL) were taken every 2 min via an indwelling atrial cannula from conscious, unrestrained animals. In the estradiol primed intact rats, a bolus injection of somatostatin (10, 100, and 1000 μg/kg) lowered PRL levels in a dose-dependent manner. When the PRL concentration was elevated by the administration of pimozide (3 mg/kg), a dopaminergic receptor blocking agent, somatostatin was ineffective in decreasing plasma PRL concentration but the PRL concentration was lowered by somatostatin when the rat had been primed with estradiol. Somatostatin had no effect on the normal HAG rats, but lowered the plasma PRL concentration in the estradiol primed HAG rats. Since somatostatin inhibits PRL secretion only in the estradiol primed rats, it is suggested that estradiol priming creates a new environment, presumably via new or altered receptors, which can be inhibited by somatostatin.
Identification and specific blockade of histaminergic receptors in guinea pig vasa deferentia
Authors: Joshi Dinesh P. , Verma Subhash C.
Published: April 2011

Histamine produces contractions of the guinea pig vas deferens. The present investigation was undertaken to characterize the nature of histaminergic receptors in this tissue. Histamine (1.6 × 10−6 M to 3.2 × 10−5 M) produced dose-related contractions of guinea pig vas deferans (GPVD). Mepyramine (5.3 × 10−8 M and 1 × 10−9 M) blocked the responses to histamine competitively. Metiamide (1.23 × 10−5 M) did not block the responses to histamine significantly. Specific H1 and H2 receptor agonists, namely 2-(2′-pyridyl)ethylamine (PEA) (2.55 × 10−6 M to 3.0 × 10−5 M) and 4-methylhistamine (4-MH) (2.52 × 10−5 M to 3.0 × 10−4 M), respectively, produced dose-related contractions of GPVD. The responses to PEA were blocked competitively by mepyramine, whereas the responses to 4-MH were blocked by metiamide. Reserpine pre-treatment (5 mg/kg, i.p., 24 h) did not alter the responses to histamine and PEA. Our data suggest the presence of both H1 and H2 receptors in the GPVD which are excitatory in nature.
Baclofen-induced decrease of excitability of primary afferents and depression of monosynaptic transmission in cat spinal cord
Authors: Čapek Radan , Esplin Barbara
Published: April 2011

The relationship of the depressant effect of baclofen on spinal monosynaptic transmission and its effect on the excitability of primary afferents was examined in spinal unanesthetized cats. Baclofen (1.0 mg/kg, i.v.) produced a deep and long-lasting depression of spinal reflex responses with a concomitant decrease of terminal excitability. Primary afferent depolarization, as indicated by an increase of terminal excitability, evoked by conditioning of an antagonistic muscle nerve, was greatly reduced by this drug. Depression of monosynaptic transmission induced by baclofen was temporarily reversed by posttetanic potentiation. However, the same high frequency orthodromic stimulation further reduced excitability of terminals. It is therefore unlikely that block of terminal invasion is responsible for baclofen-induced depression of spinal monosynaptic transmission. These results are compatible with the suggestion that baclofen causes a reduction of transmitter release. In the spinal cord, this action is probably limited to the excitatory transmitter of primary afferents.
Uptake of cytidine by isolated, perfused mouse liver
Authors: Kolassa Norbert , Paterson Alan R. P.
Published: April 2011

Mouse livers were perfused at 22 °C with an oxygenated salts medium containing [5−3H]cytidine and [carboxyl-14C]inulin. The cellular uptake of cytidine was determined from the 3H content of liver samples less that present in the extracellular (inulin) space of the samples. Time courses of cytidine uptake were biphasic with initial phases which were approximately linear for 15 s and had time zero values that approximated the extracellular space. Rates of cytidine uptake derived from the initial phase of uptake evidently represented rates of membrane transport because (i) initial rates were saturable, and (ii) cytidine uptake was blocked by the nucleoside transport inhibitor, nitrobenzylthioinosine (NBMPR). Treatment of mice with the 5′-monophosphate of NBMPR (> 0.2 mg/kg, injected i.p.) 30–40 min prior to the perfusion also blocked cytidine entry into livers. An apparent half-saturation constant of about 10−3 M and a maximum rate of about 1 μmol∙g−1∙min−1 were estimated for the NBMPR-sensitive transport of cytidine into mouse liver cells.
Selective inhibitory synapse loss in chronic cortical slabs: a morphological basis for epileptic susceptibility
Authors: Ribak Charles E. , Reiffenstein R. J.
Published: April 2011

Electron microscopic examination of pyramidal neurones at the edges of chronic slabs of cerebral cortex in the cat revealed a selective loss of inhibitory (symmetric axosomatic) synapses compared with pyramidal neurones in the centers of the slabs. It appears likely that the neurons at the edges, which retain excitatory input (asymmetric axodendritic synapses) in the neuropil, but totally lack the somatic inhibitory input, act as the focus for the prolonged seizure activity which occurs in chronic cortical slabs.
Differential sensitivity of hepatic microsomal aryl hydrocarbon hydroxylase to the inhibitory effect of SKF 525-A in rats of varying age, hormonal- and drug-induced status
Authors: Gontovnick L. S. , Bellward G. D.
Published: April 2011

The inhibition of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity by SKF 525-A in vitro was studied in hepatic microsomes from rats of varying age, sex hormone status, and drug treatment. The concentration of SKF 525-A required to produce a 50% inhibition of AHH activity, the IC50, was determined for the various microsomal preparations. Microsomes from adult female and immature rats exhibited a similar sensitivity to SKF 525-A. However, microsomes from adult male rats were significantly more sensitive to the inhibitory effect of the drug. AHH activity from pseudohermaphroditic male rats was found to have the same sensitivity to SKF 525-A as in the female littermates. Microsomes obtained from adult rats that had been pretreated with various cytochrome P-450 inducing agents yielded significantly different IC50 values from untreated controls. These differences in IC50 values indicated that the predominant form(s) of cytochrome P-450 that hydroxylate benzo(a)pyrcne varied with the age, hormonal, and induced status of the animal.
Beta2-mediated hypotension and myocardial injury
Authors: Brown-Lukacsko Alison , Lukacsko Peter
Published: April 2011

This study was designed to investigate the importance of beta2 receptor mediated hypotension in the pathogenesis of myocardial injury. The effect of isoproterenol and the putative beta2 agonist albuterol on arterial blood pressure, heart rate, the myocardial content of ATP and cAMP, and the serum content of MB-CPK was examined in conscious rats. Isoproterenol (5.25 mg/kg, s.c.) and albuterol (45 mg/kg, s.c.) lowered blood pressure and elevated heart rate to the same extent. Also, both agonists increased the myocardial content of cAMP, decreased the myocardial content of ATP, and elevated serum MB-CPK. The beta1 antagonist practolol, but not the ganglionic blocking agent chlorisondamine, attenuated the elevation in heart rate to albuterol without reducing its effect on blood pressure. Practolol, but not chlorisondamine, abolished the effects of albuterol on cAMP, ATP, and MB-CPK. These data suggest that the myocardial injury which is associated with an increased heart rate and changes in cAMP, ATP, and MB-CPK following the administration of albuterol is not the result of beta2-mediated hypotension, but is due to stimulation of myocardial beta1 receptors.
Changes in plasma Cortisol and progesterone after administration of enkephalins to newborn lambs
Authors: Carson George D. , Challis John R. G.
Published: April 2011

Methionine-enkephalin and leucine-enkephalin were injected into the brachiocephalic artery of lambs at 8–18 days of age. There was a significant increase in the concentration of Cortisol in plasma 15 – 30 min after leucine-enkephalin (10-, 100-, and 500-μg bolus). After the 100-μg bolus, there was a biphasic response and a second significant rise in Cortisol was seen at 90 min. Plasma progesterone was elevated significantly at 15–30 min and at 90 min after the 100- and 500-μg injections of leucine-enkephalin. Methionine-enkephalin (100 μg) produced a transient rise in plasma Cortisol at 15 – 30 min, although the mean concentrations were not statistically different from the control period. We conclude that in newborn lambs, enkephalins may influence adrenal function. It is likely that such an action is secondary to effects on brain or pituitary hormone release.
Effects of chest wall compressions in kittens
Authors: Trippenbach T. , Gaultier C. , Cooper L.
Published: April 2011

Effects of chest compressions on the pattern of breathing were studied in pentobarbital anaesthetized 9- to 11-day-old kittens before and after vagotomy. The chest was compressed by means of a micrometer at three levels (T1–4, T6–8, T9–11). In intact and vagotomized kittens, the group mean values of inspiratory time (tI), expiratory (tE) time, peak amplitude of the integrated phrenic activity (PHR) and its rate of rise (PHR/tI) during compressions were not different from those of the control breaths. On the other hand, in intact kittens during chest compressions variability of all the measured variables significantly increased. In the vagotomized kittens, variability of parameters other than inspiratory time was unaffected. Nevertheless we cannot exclude contribution of extravagal receptors in control of tE. The tE effects could be masked by the increased variability of the control value in vagotomized kittens. The effects of chest compression on the integrated phrenic activity were mostly dependent on the intact vagal feedback.
Investigations into the role of sulfhydryl groups in the mechanism of action of the nitrates
Authors: Moffat J. A. , Armstrong P. W. , Marks G. S.
Published: April 2011

The mechanism by which nitroglycerin (GTN) initiates relaxation in vascular smooth muscle is not known. According to one hypothesis a specific nitrate receptor exists with a key sulfhydryl (SH) group in the active site. The current study was performed with sulfhydryl reagents in helical strips of the canine medial saphenous vein from 20 dogs to examine the role of the SH group in the action of GTN. The reagents used were 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) and p-chloromercuribenzoate (PCMB) which bind to and inactivate SH groups, and dithiothreitol (DTT), an SH reducing agent. It was anticipated that DTNB and PCMB would decrease the sensitivity to GTN while DTT might increase the sensitivity to GTN. Treatment of strips with PCMB and DTNB did not alter the dose–response curves for GTN. In contrast, following DTT treatment (1 × 10−4 M) the maximum response to GTN (10−5 M) was significantly reduced from 80.3% ± 4.0 (SD) in control strips to 46.9% ± 4.4 (SD) in the treated strips. These data suggest that relaxation induced by GTN in vascular smooth muscle occurs by a mechanism other than interaction with membrane SH groups.
Manganese neurotoxicity: a model for free radical mediated neurodegeneration?
Authors: Donaldson John , McGregor Duncan , LaBella Frank
Published: April 2011

In man, manganese neurointoxication is characterised in the early phase by bizarre behavior reminiscent of that observed in schizophrenia. During chronic manganese intoxication the neuropsychiatric symptoms manifested earlier disappear and are followed by a permanent neurological phase typified by extrapyramidal symptoms similar to those of Parkinson's disease. Study of manganese intoxication in animals may provide important clues towards elucidation of the biochemical defect underlying neuropsychiatric as well as extrapyramidal diseases. Investigations in our laboratory suggest that neurotoxicity of manganese is an exaggeration of function in normal neuronal homeostasis. Manganese neurointoxication in neonatal rats resulted in significant depression of lipid peroxidation in several rat brain regions examined. In the striatum, lipid peroxidative activity was abolished, an effect which may be related to alteration in neurotransmitters often observed in the striatum of manganese-treated rats. The chronic, extrapyramidal stage of manganism, may ensue when excess Mn2+ is oxidised to higher valency forms where it can potentiate the autoxidation of catecholamines, like dopamine, resulting in concomitant formation of free radicals and cytotoxic quinones. This latter effect may arise preferentially in the substantia nigra, where neuromelanin is formed nonenzymatically by autoxidation of dopamine.
Role of the pituitary in the effects of tonin on adrenal secretion of the rat
Authors: Schiffrin Ernesto L. , Garcia Raul , Gutkowska Jolanta , Genest Jacques
Published: April 2011

Chronically catheterized conscious rats were infused intravenously with tonin at 2.4 and 12 μg∙kg−1∙min−1 for 2 h. Plasma aldosterone concentration (PAC) at the end of the experiment was 11.2 ± 2.4 ng% in controls, 8.5 ± 2.8 ng% in rats infused with tonin at the lower rate, and 26.2 ± 3.6 ng% (p < 0.01 vs. controls) in rats infused at the higher rate. Plasma corticosterone (PC) was significantly higher (p < 0.05) in the group infused at the high rate while plasma renin activity (PRA) was significantly reduced in this group of rats. Plasma angiotensin II (AII) concentration was similar in all three groups. PAC was elevated after tonin infusion in the presence of AII blockade. PAC in conscious sodium-depleted rats infused with tonin was not significantly changed, but PRA was significantly reduced (p < 0.01). In chronically hypophysectomized rats, PAC remained unchanged by tonin infusion. The failure of tonin to stimulate aldosterone in hypophysectomized animals indicates a role of a pituitary hormone (probably ACTH) in the effect of tonin on adrenal secretion.
Static elastic studies of lathyritic rabbit carotid arteries and thoracic aorta
Authors: Terpin Teresa , Roach Margot R.
Published: April 2011

Sixteen New Zealand White rabbits with an average initial weight of 1.6 kg were used to determine if lathyrism altered the static elastic properties of the aorta and carotid arteries. Eight were given 1% β-aminopropionitrile in their drinking water for the same period. All were fed regular rabbit chow. Blood pressures and body weights were taken twice weekly. Blood pressure was not significantly different between the two groups but the lathyritic animals did lose weight while the controls gained. The rabbits were sacrificed at the end of 4 weeks with an overdose of sodium pentobarbital (Nembutal) and the carotid arteries and thoracic aorta were removed for pressure–volume experiments. From these experiments tension–strain curves, elastances, and slack of the collagen were obtained. The longitudinal distensibility curves for the aortas and carotid arteries for both groups were almost identical. The longitudinal elastances of elastin and collagen, and the slack were not significantly different between the two groups. The circumferential-distensibility curves for the same arteries showed few differences, however, the elastances of elastin and collagen, and the slack decreased indicating an alteration in the elastin and a decrease in collagen fibres or a defect in the intramolecular cross-links of collagen.
Primary afferent depolarization in frog spinal cord is associated with an increase in membrane conductance
Authors: Padjen Ante L. , Hashiguchi Toshio
Published: April 2011

The mechanism of primary afferent depolarization (PAD) was studied in the isolated frog spinal cord using intrafibre recording (microelectrodes filled with 0.6 M potassium sulfate) from large myelinated axons of dorsal roots. Standard current–clamp technique was used to obtain voltage–current (V–I) relationship. It was found that: (i) PAD is voltage dependent: its amplitude and rate of rise are increased with hyperpolarization; (ii) the slope of the linear part of the V–I curve obtained during PAD is decreased compared with the V–I curve at rest; (iii) the PAD equilibrium potential, estimated by extrapolation, ranged from −66 to −40 mV. These results suggest that PAD is associated with an increase in conductance of primary afferent terminals and thus seem to provide the first experimental evidence for the hypothesis that shunting of primary afferent membrane is the mechanism of presynaptic inhibition in the vertebrate nervous system.
Artifactual production and recovery of acetaldehyde from ethanol in urine
Authors: Giles H. G. , Meggiorini S.
Published: April 2011

Ethanol (1575 mg/L) incubated with fresh urine from healthy, ethanol-free subjects yields acetaldehyde. The concentration of acetaldehyde depends upon temperature, time of incubation, and pH. In samples made hypertonic with sodium chloride (200 mg/mL) and in samples filtered through 0.45-μm membranes, acetaldehyde production was not decreased. L-Ascorbic acid (0.1 mg/mL) added to normal pooled urine caused a threefold increase in acetaldehyde production but thiourea (7.6 mg/mL) stopped it. This suggests that the oxidation of ethanol to acetaldehyde is catalyzed by the semidehydroascorbate peroxy radical of ascorbic acid. Recovery of acetaldehyde added to urine was less than 100% over the pH range 1.5 to 10. Relative to blood, artifactual production of acetaldehyde from ethanol in urine is more easily controlled and is up to an order of magnitude less but corrections for the variables above are still required.
Vasorelaxing actions of molsidomine and its metabolites, in comparison with nitroglycerin
Authors: Muramatsu Ikunobu , Fujii Kazutoshi , Sakakibara Yoshihiko , Fujiwara Motohatsu
Published: April 2011

The effect of a novel antianginal agent, molsidomine (N-ethoxycarbonyl-3-morpholinosydnonimine) (SIN-10) and its metabolites, 3-morpholinosydnonimine (SIN-1) and N-nitroso-N-morpholinoaminoacetonitrile (SIN-1A) on isolated dog blood vessels were investigated. SIN-1 and SIN-1A elicited a concentration-dependent relaxation of prostaglandin F2α contracted strips, while SIN-10 was without effect even in a concentration of 10−4 M. The mean effective concentration (EC50) values of SIN-1A were much lower than SIN-1 and other vasodilators including nitroglycerin. The time course of relaxation was more rapid and transient in response to SIN-1A than to SIN-1. Adrenergic and cholinergic blocking agents did not affect the relaxing responses to SIN-1 and SIN-1A. SIN-1A also attenuated the norepinephrine-, KCl-, Ca2+-, or electrical transmural stimulation-induced contractile response, but SIN-1A increased the [3H]norepinephrine release from the adrenergic nerve terminals in response to transmural stimulation. Methemoglobin, which reportedly binds nitric oxide, or methylene blue, an inhibitor of guanylate cyclase, attenuated the relaxing response to SIN-1A. These results indicate that the vasodilating action of molsidomine results from the direct action on the vascular smooth muscle and suggest that the action is caused by its metabolites, probably SIN-1A, which contains a nitric oxide-moiety in the molecule. The possible mechanism of vasorelaxing action of SIN-1A is discussed in comparison with that of nitroglycerin.
Dynorphin and enkephalins in adrenal paraneurones. Opiates in the adrenal medulla
Authors: Lemaire Simon , Day Robert , Dumont Michel , Chouinard Lucie , Calvert Raymond
Published: April 2011

Immunoreactive dynorphin (ir-Dyn), immunoreactive leucine-enkephalin (ir-Leu-Enk) and various other neuropeptides were measured in acid extracts of bovine adrenal medulla and isolated adrenal chromaffin cells. Their respective levels ranged as follows: Leu-Enk > Dyn > bombesin > vasoactive intestinal peptide (VIP) > neurotensin > substance P. Comparisons of the total catecholamine levels with the levels of Leu-Enk in both extracts gave ratios in the same order of magnitude (2600, tissue extract and 5000, cell extract). However, the catecholamine/Dyn ratio in the tissue extract (138 000) was much higher than that found in the cell extract (20 180), suggesting a possible selective degradation of Dyn in tissue extract as compared with cell extract or an induction of Dyn biosynthesis in cells which have been isolated from their natural microenvironment. Immunofluorescence staining of isolated chromaffin cell sections revealed the presence of ir-Dyn in 5 to 10% of the total cell population. To localize ir-Dyn in regard to Leu-Enk and catecholamines, adrenal chromaffin cells were separated into three populations (I, II, and III) on a stepwise bovine serum albumin (BSA) gradient. Relative high levels of ir-Dyn were measured in cell layer I (4 pmol/106 cells), a cell population enriched in noradrenaline. However, ir-Leu-Enk was more concentrated in cell layers II and III (5.3 and 8.3 pmol/106 cells), two populations enriched in adrenaline. Isolation and high pressure liquid chromatography (HPLC) analysis of adrenomedullary Dyn indicated the presence of at least five molecular forms corresponding to Dyn-(1-11), Dyn-(1-12), Dyn-(1-13), Ala-containing-Dyn-(1-13) and a nonidentified molecule eluting closely to Dyn-(1-13). These data indicate that adrenal ir-Dyn and ir-Leu-Enk have distinct cellular distributions. In addition, the identification of Dyn fragments in bovine adrenal medulla indicates that these short peptides may be considered as natural active forms of Dyn.
Cytosolic enzyme leakage from isolated smooth muscle preparations
Authors: Baer Hans P. , Vriend Richard A.
Published: April 2011

Several isolated smooth muscle preparations were shown to release cytosolic enzymes including adenosine deaminase, lactate dehydrogenase, and nucleoside phosphorylase under experimental conditions resembling those used in contractility or drug uptake studies. This enzyme leakage indicates significant general cell damage and suggests that experiments dealing with drug metabolism, binding, and uptake in isolated tissues must be interpreted with caution.
Functional anatomy of the canine mediastinal cardiac nerves located at the base of the heart
Authors: Brandys J. C. , Randall W. C. , Armour J. A.
Published: April 2011

The major canine cardiopulmonary nerves which arise from the middle cervical and stellate ganglia and the vagi course toward the heart in the dorsal mediastinum where they form, at the base of the heart dorsal to the pulmonary artery and aorta, the dorsal mediastinal cardiac nerves. In addition, the left caudal pole and interganglionic nerves project onto the left lateral side of the heart as the left lateral cardiac nerve. These nerves contain afferent and (or) efferent axons which, upon stimulation, modify specific cardiac regions and (or) systemic pressure. In addition, with the exception of the left lateral cardiac nerve, stimulation of each of these nerves produces compound action potentials in the cranial ends of the majority of the major cardiopulmonary nerves demonstrating that axons in each dorsal mediastinal cardiac nerve interconnect with axons in the majority of the cardiopulmonary nerves. Axons in the left lateral cardiac nerve connect primarily with axons in the left caudal pole and left interganglionic nerves. The dorsal mediastinal nerves project distally onto the heart as coronary nerves accompanying the right or left coronary arteries. These innervate the ventricular myocardium which is supplied by their respective vessels. The left lateral cardiac nerve projects directly onto the lateral epicardium of the left ventricle. The dorsal mediastinal and left lateral cardiac nerves are the major sympathetic cardiac nerves. Thus, the cardiac nerves located in the mediastinum at the base of the heart are not simple extensions of cardiopulmonary nerves, but rather have a unique anatomy and function of their own.
α-Adrenoceptor blockade and class III antiarrhythmic activity combined: hemodynamic and electrophysiological effects of melperone in the dog
Authors: Platou Eivind S. , Myhre Eivind S. P. , Refsum Helge
Published: April 2011

Melperone has been found to possess vasodilating and slight positive inotropic properties in addition to its class III antiarrhythmic action. To determine whether some of these effects might be related to an α-adrenoceptor blocking action of melperone, phenoxybenzamine (10 mg/kg) was given as a 2-h infusion to 12 pentobarbital-anesthetized dogs. In addition, six of the dogs were given atenolol 0.5 mg/kg i.v. After a 1-h stabilizing period, melperone (0.5,2.5, and 12.5 mg/kg) was given i. v. in cumulative doses to both series of dogs. In the presence of α-blockade as well as combined α- and β-blockade, atrial, atrioventricular (AV) nodal, and ventricular refractoriness increased and heart rate and AV nodal conduction time decreased, as previously reported after addition of melperone alone. A slight increase in left ventricular (dP/dt)max occurred after the addition of melperone (2.5 mg/kg) in the presence of α- and β-blockade, but only after the highest dose of melperone were small decreases in blood pressure and total peripheral resistance induced. The present study indicates that melperone combines the properties of class III antiarrhythmic action, slight positive inotropy, and α-adrenoceptor mediated vasodilation.
Tetrodotoxin-resistant relaxation to transmural nerve stimulation in canine saphenous veins: a possible neural origin
Authors: Senaratne Manohara P. J. , Kappagoda Tissa
Published: April 2011

Transmural nerve stimulation following sympathetic (guanethidine 10−4 mol/L, phenoxybenzamine 2 × 10−5 mol/L, propranolol 2 × 10−6 mol/L) and muscarinic blockade (atropine 5 × 10−5 mol/L) produces a relaxatory response in canine saphenous veins contracted with prostaglandin F2α. This relaxatory response was shown previously to be resistant to tetrodotoxin. Transmural nerve stimulation (10 V, 1.0 ms) was applied as intermittent trains of stimuli of 30 s duration at frequencies of 1–32 Hz. The veins showed a frequency dependent relaxation (maximum 2.65 ± 0.20 g). The stimulations were repeated in the presence of lignocaine (10−3 mol/L), apamin (10−8 mol/L), ascorbic acid (10−4 mol/L), or catalase (50 μg/mL). The relaxatory response was unaffected by apamin, scorpion toxin, superoxide dismutase, ascorbic acid, and catalase (p > 0.05). However, lignocaine (10−3 mol/L) reduced significantly the relaxatory response to transmural nerve stimulation in this preparation (p < 0.05). In a separate group of veins, lignocaine (10−3 mol/L)l abolished the contractile response to transmural nerve stimulation with little effect upon the contractile response to exogenous noradrenaline and the relaxatory responses to isoprenaline and sodium nitrite. These findings support the proposition that the nonadrenergic, noncholinergic tetrodotoxin-resistant relaxatory response observed with transmural nerve stimulation in the canine saphenous vein is mediated by a neural mechanism.