bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of chronic ethanol and food deprivation on intestinal villus morphology and brush border membrane content of lipid and marker enzymes
Authors: Keelan M. , Walker K. , Thomson A. B. R.
Published: April 2011

Brush border membranes (BBM) were isolated from the jejunum and ileum of control, ad libitum (CAL); control, food-restricted (CFR); control, weight gain (CWG); and ethanol-fed (EF) rabbits. Jejunal alkaline phosphatase activity was similar among control groups, but higher in CAL than EF animals. Sucrase activity was higher in EF and CWG animals than in CAL and CFR. The alkaline phosphatase/sucrase ratio was lower in EF than control animals. Ileal enzyme marker activity was similar among EF and control animals. Sucrase (S) activity was lower in the ileum than in the jejunum. Jejunal free fatty acid and phospholipid/cholesterol (PL/C) were lower in EF than control animals, whereas ileal lipid content was generally similar among all animal groups. Total phospholipid content was similar between sites, but the cholesterol and free fatty acid content were lower in the ileum than the jejunum. The phospholipid/cholesterol ratio was increased only in the ileum of EF animals. The amount of lecithin was decreased in the jejunal BBM of EF animals resulting in a decreased choline/amine phospholipid ratio as compared with control animals. The ileal phospholipid composition was similar among all groups. A large increase in villus height is observed in the jejunum of EF animals. Villus surface area and mucosal surface area are altered with ethanol feeding and food deprivation. Thus, (i) there is a gradient of S and cholesterol between the BBM of jejunum and ileum; (ii) changes in food intake are associated with changes in the morphology as well as the enzyme marker and lipid content of BBM; and (iii) ethanol feeding is associated with a decline in PL/C, a decrease in the amount of lecithin, and a decrease in the choline/amine PL ratio in the jejunal BBM. It is proposed that changes in the BBM lipid content owing to ethanol feeding may influence intestinal permeability and thereby explain the previously reported effect of chronic ethanol feeding on the intestinal uptake of lipids.
Partial purification of a hypertensive substance from rat erythrocytes
Authors: McCumbee William D. , Wright Gary L.
Published: April 2011

A crude extract prepared from rat erythrocytes was previously shown to contain an active component (hypertensive factor, HF) that stimulates the in vitro uptake of calcium by aortic rings and causes a sustained and severe elevation in systolic blood pressure in normotensive rats. The present report demonstrates that the in vitro effects of HF on calcium uptake are concentration dependent and reversible, and that these effects on calcium uptake provide a convenient bioassay for monitoring the purification of HF. HF was prepared from a diffusate obtained by dialyzing hemolyzed rat erythrocytes. The diffusate was applied successively to molecular sieve and anion exchange columns resulting in a 1500-fold increase in specific activity relative to the starting hemolysate. The compound stimulating calcium uptake was found to be heat stable and resistant to digestion with trypsin and chymotrypsin. In contrast, treatment with pronase E, a nonspecific protease, markedly increased the calcium transport stimulatory activity. The administration of the purified preparation to normotensive rats having a systolic blood pressure of 118 ± 2 Torr (1 Torr = 133.322 Pa) resulted in a significant elevation of blood pressure (171 ± 11 Torr) by day 5. The severity of this increase further suggests that there is a marked enhancement in potency relative to earlier fractions that were examined. Perhaps most importantly, these results indicate that, at this stage of purification, the pressor component and the calcium-stimulatory component of HF appear to co-purify.
The influence of temperature and frequency of stimulation on the impairment of excitability of frog skeletal muscle by local anesthetics and alkyl amphipathic agents
Authors: Foulks James G. , Morishita Lillian
Published: April 2011

The potency of various types of alkyl amphipathic (cationic, anionic, and neutral) as well as tertiary amine local anesthetics in impairing the excitability of frog skeletal muscle was markedly enhanced by an increase in temperature from 20 to 30 °C. Enhancement of the local anesthetic effects of all types of agents was also produced by a decrease in temperature to 5 °C, but this effect was found to be frequency dependent. With abrupt increase or decrease in temperature, changes in excitability were rapid and unlikely to be the result of changes in the partition of the apolar portions of these molecules into the hydrophobic regions of the sarcolemma. These results are interpreted as indicating that both the presence of local anesthetics and alterations in temperature can influence the rates of potential-dependent changes in the conformation of membrane proteins that control the permeability of excitable sodium channels, possibly by modifying the fluidity of specific portions of their hydrophobic components or their immediate lipid environment. The accumulation of inactivation as the result of incomplete recovery from the effects of preceding depolarizations appears sufficient to explain the frequency-dependent effects produced by these agents.
Electrophysiological observations on diaphragm muscle from normal and dystrophic hamsters
Authors: Hunter E. G. , Elbrink J.
Published: April 2011

The cellular electrical activity of diaphragm from F1B normal and BIO 14.6 dystrophic hamsters has been investigated using microelectrodes. Resting membrane potentials and action potentials were recorded from control muscles and from muscles exposed to 2,4-dinitrophenol. The action potentials of normal and dystrophic diaphragms were similar in amplitude and configuration. Treatment with 2,4-dinitrophenol caused the action potential amplitude of both diaphragms to decline by similar amounts. The control resting membrane potential of diaphragm from dystrophic hamsters is not significantly different from that of normal hamsters. Treatment with 2,4-dinitrophenol caused a linear decrease in the resting membrane potentials of both groups of muscles. Dystrophic muscle, however, showed a more rapid decline in excitability when exposed to 2,4-dinitrophenol. This suggests that adenosine triphosphate production in dystrophic muscle is partially inhibited as has been suggested by other workers.
Effect of aldosterone on vascular angiotensin II receptors in the rat
Authors: Schiffrin Ernesto L. , Franks Douglas J. , Gutkowska Jolanta
Published: April 2011

The effect of aldosterone on the density and affinity of binding sites for 125I-labelled angiotensin II was investigated in a particulate fraction prepared from the rat mesenteric arteriolar arcades. The infusion of aldosterone 6.6 μg/h intraperitoneally via Alzet osmotic minipumps for 6 d produced an increase in the density of binding sites for 125I-labelled angiotensin II without change in affinity. After sodium depletion, mesenteric artery angiotensin II receptors were down-regulated as expected. An increase in the number of binding sites could be found when aldosterone was infused into sodium-depleted rats with no change in the elevated plasma renin activity. The intraperitoneal infusion of angiotensin II (200 ng ∙ kg−1 ∙ min−1 for 6 d) simultaneously with aldosterone resulted in down-regulation of vascular angiotensin II receptors, whereas after intravenous angiotensin II infusion (at 60 ng ∙ kg−1 ∙ min−1) the density of angiotensin II binding sites rose with aldosterone infusion. Plasma renin activity (PRA) was reduced and plasma angiotensin II increased in a dose-dependent fashion after angiotensin II infusion. An aldosterone concentration of 3 ng/mL for 18 h produced an increase in the number of angiotensin II binding sites in rat mesenteric artery smooth muscle cells in culture. We conclude that increased plasma aldosterone may result in up-regulation of vascular angiotensin II receptors independently of changes in plasma renin activity, and may in certain physiological states effectively antagonize the down-regulating action of angiotensin II.
Resection of rabbit ileum: effect on brush border membrane enzyme markers and lipids
Authors: Keelan M. , Walker K. , Thomson A. B. R.
Published: April 2011

Alterations in transport function have been described 6 weeks after surgical resection of 50% of the distal small intestine. Previous studies demonstrated a modest increase in the jejunal uptake of medium chain length fatty acids following resection, while the uptake of many other lipids (cholesterol, bile acids, fatty alcohols, short and long chain length fatty acids) appears to be unaffected. Marked changes in the kinetic constants for the carrier-mediated uptake of four sugars and leucine were observed following resection, but the changes in transport were not associated with changes in the mucosal surface area. This study was undertaken to examine the possible adaptive mechanisms that occur with ileal resection in the rabbit. A 29% increase in the wet weight of jejunal mucosal scrapings and a 53% increase in jejunal brush border membrane (BBM) protein was observed following resection. The jejunal BBM sucrase (S) was unchanged following ileal resection, but alkaline phosphatase (AP) total activities were increased in the resected rabbits. This resulted in a 45% increase in the ratio of AP/S with resection. The lipid composition (total free fatty acids, total bile acids, total cholesterol, total phospholipids, individual phospholipids, and the ratio of total phospholipids/total cholesterol) of BBM was similar in control and resected rabbits. This suggests that quantitative rather than qualitative changes in the membrane composition may be responsible for the transport changes observed in resected animals.
Modulation of rat hepatic microsomal testosterone hydroxylases by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related toxic isostereomers
Authors: Keys Barbara , Hlavinka Michelle , Mason Grant , Safe Stephen
Published: April 2011

The effects of several toxic halogenated aryl hydrocarbons including 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, 2,3,4,7,8-pentachlorodibenzofuran, 3,3′,4,4′-tetrabromobiphenyl, 3,3′,4,4′5-pentachlorobiphenyl, and 3,3′,4,4′-tetrachloroazobenzene on hepatic microsomal testosterone hydroxylases were determined in the immature male rat. All of these compounds induced hepatic testosterone 7α-hydroxylase and inhibited testosterone 6β-, 16α-, 16β-, and 2α-hydroxylases and androstenedione formation. It was observed that there was a good correlation between the increase in testosterone 7α-hydroxylase by the halogenated hydrocarbons and their ability to cause body weight loss in the exposed rats. Comparable linear correlations were observed between toxicity and the decreased activities of other testosterone hydroxylases. The role of altered testosterone metabolism in the toxicity of halogenated aryl hydrocarbons is unknown.
Metabolic and hormonal effects of test meals with various protein contents in pigs
Authors: Rérat A. , Chayvialle J. A. , Kandé J. , Vaissade P. , Vaugelade P. , Bourrier T.
Published: April 2011

The postprandial release of immunoreactive insulin, glucagon, gastrin, somatostatin, pancreatic polypeptide (PP), and gastric inhibitory polypeptide (GIP) was studied in parallel with the absorption of sugars and amino acids in conscious pigs. Six pigs fitted with permanent catheters in the portal vein and arterial blood system as well as with an electromagnetic flow probe around the portal vein received successively at 3-day intervals, three meals of 800 g each containing 0, 14, or 28% protein (semisynthetic diets based on fish protein). Blood samples were collected and portal blood flow was recorded during a postprandial period of 8 h. For the same level of feed intake, an increase in the dietary protein concentration led to a higher alpha-amino nitrogen absorption and to a lower appearance of reducing sugars in the portal vein; in addition, the carbohydrate absorption efficiency (amounts absorbed as a percentage of amounts ingested) was reduced, showing the competition between the absorption of amino acids and glucose. The largest absorption occurred during the first 4 h after the meal, but neither the digestion of proteins nor that of carbohydrates were finished 8 h after the meal since portoarterial differences could still be observed. All test meals induced a rise of portal and peripheral concentrations of insulin, gastrin, somatostatin, and PP, and of the systemic level of GIP. Glucagon increased after the 28% protein meal only. The rise of plasma insulin paralleled that of blood glucose, and bore a significant positive relationship to the systemic GIP level in the early postprandial period. In terms of absolute amounts, portoarterial concentration gradients increased postprandially. Insulin release was significantly the highest after intake of the 14% protein diet. The gastrin response was significantly correlated to the amount of protein. Similarly the release of glucagon and somatostatin tended to increase with increasing dietary amount, but differences failed to reach significance (P < 0.05), except for glucagon 2 h after the meal. There were very close relationships between the hourly amounts of alpha-amino nitrogen absorbed and gastrin and glucagon production, as between insulin and PP secretions. From the present results, the induction of physiological increments of plasma peptide concentration in 60-kg pigs would require infusion rates of about 50–250 μg/h for insulin, 1–4 μg/h for gastrin 17, 5–10 μg/h for glucagon and somatostatin, and 5–50 μg/h for PP.
Effect of the blood lactate concentration on renal glutamine metabolism in dogs with chronic metabolic acidosis
Authors: Halperin Mitchell L. , Chen Ching B. , Cheema-Dhadli Surinder
Published: April 2011

It appears that glutamine and lactate are the principal substrates for the kidney in dogs with chronic metabolic acidosis. Accordingly, the purpose of this study was to determine if a higher or lower rate of renal lactate extraction would influence the rate of glutamine extraction at a constant rate of renal ATP turnover. The blood lactate concentration was 0.9 ± 0.01 mM in 15 acidotic dogs. However, eight dogs with chronic metabolic acidosis had a spontaneous blood lactate concentration of 0.5 mM or lower. The kidneys of these dogs extracted considerably less lactate from the arterial blood (19 vs. 62 μmol/100 mL glomerular filtration rate (GFR)). Nevertheless, glutamine, alanine, citrate, and ammonium metabolism were not significantly different in these two groups of dogs. Renal ATP balance in acidotic dogs with a low blood lactate could only be achieved if a substrate other than additional glutamine were oxidized in that segment of the nephron which normally oxidized lactate; presumably a fat-derived substrate and (or) lactate derived from glucose was now the metabolic fuel at these more distal sites. When the blood lactate concentration was greater than 1.9 mM, lactate extraction rose to 219 μmol/100 mL GFR. Glutamine, alanine, citrate, and ammonium metabolism were again unchanged; in this case, ATP balance required substrate flux to products other than carbon dioxide, presumably, gluconeogenesis. It appears that renal ammoniagenesis is a proximal event and is independent of the rate of renal lactate extraction.
Inhibition of monoamine oxidase by amiloride
Authors: Palatý Vladimír
Published: April 2011

Amiloride was found to lower the overflow of 3,4-dihydroxyphenylethylene glycol from isolated rat tail artery. The overflow was reduced to about 50% in the presence of 10−5 M concentration of the drug. Reduced overflows of the glycol were observed also under conditions when the nonexocytotic release of endogenous noradrenaline was enhanced by tyramine, reserpine, or by the elevation of external K+ in the absence of extracellular Ca2+. They were accompanied by increased overflows of the amine. Amiloride inhibited monoamine oxidase activity (E.C. 1.4.3.4) of the A form in rat brain homogenate by acting as a competitive inhibitor.
The role of the pituitary–adrenal axis in the hyperthermia induced by acute peripheral or central (preoptic anterior hypothalamus) administration of morphine to unrestrained rats
Authors: Thornhill J. A. , Saunders W. S.
Published: April 2011

The role of the pituitary–adrenal axis in the mediation of morphine-induced hyperthermia of conscious, unrestrained rats was investigated. Rectal (TR) and tail (Tt) temperatures and oxygen uptake rates [Formula: see text] were measured following peripheral or central injection of morphine sulphate (MS) in groups of Sprague–Dawley rats before and after adrenalectomy (adx), hypophysectomy (hyp), or pituitary suppression (via dexamethasone treatment). The hyperthermic TR responses of groups given MS either subcutaneously (5 or 15 mg/kg) or directly into the preoptic anterior hypothalamus (POAH, 1 or 10 μg/μL) before adx were not different upon retesting with the same dose of MS 2 weeks later following adx. The hyperthermia with MS was not caused by vasoconstriction or by increases in basal metabolic rate, for Tt rose after the opiate injections whereas oxygen uptake rates [Formula: see text] were reduced. Unexpectedly, the TR following POAH injections of sterile saline (SS) or deionized water after adx increased from those seen before adx. Adx groups supplemented with dexamethasone phosphate (either chronically with 20 μg/kg daily for 2 weeks post-adx before retesting with MS or acutely with 250 μg/kg 2 h before retesting) showed a hyperthermia to MS (5 mg/kg sc or 1.0 μg/μL POAH) similar to that seen before adx. However, dexamethasone phosphate (250 μg/kg) supplementation to adx rats, that received POAH injections of SS, did reduce the rise in TR. Hyp rats given MS (5 mg/kg, sc) also evoked hyperthermic responses similar to those of non-hyp control groups. The results clearly show that the acute hyperthermia of unrestrained rats induced by either peripheral or central injections of morphine is not caused by activation of the pituitary–adrenal axis.
Arginine esterase from isolated dog prostate secretory granules is fully active enzymatically
Authors: Frenette Gilles , Dubé Jean Y. , Marcotte Jean R. , Tremblay Roland R.
Published: April 2011

We have isolated secretory granules from dog prostate homogenates and have determined whether a major portion of arginine esterase was localized in this fraction and if it was enzymatically active. Secretory granules were purified by density gradient centrifugation on sucrose, metrizamide, or Percoll. A major proportion of whole prostate homogenate arginine esterase was found in the granule fractions. Furthermore, the specific enzymatic activity in the granules was similar to the one observed in seminal plasma. No evidence could be found for the existence of significant amount of a zymogen inactive form of arginine esterase. These results suggest that arginine esterase could be active within the secretory granules in vivo and that it could hydrolyze protein substrates contained in this organelle.
Effects of chronic streptozotocin-induced diabetes on the cardiac responses to milrinone
Authors: Goyal Ramesh K. , McNeill John H.
Published: April 2011

We have studied the effects of milrinone on various cardiac preparations obtained from 6-week streptozotocin diabetic rats. The basal rate of spontaneously beating right atrium from diabetics was significantly lower as compared with controls. Milrinone (5 × 10−5 to 8 × 10−4 M) produced a dose-dependent positive inotropic and positive chronotropic effect in left atrium and right atrium, respectively. The positive chronotropic response to milrinone was slightly increased in right atria from diabetic animals. In papillary muscle neither the maximum response nor the pD2 value of milrinone was altered significantly in diabetic animals. The pD2 values of milrinone in right atrium and left atrium were found to be significantly higher in diabetic preparations compared with controls. The data indicate that the responses to milrinone are either unchanged or enhanced in hearts from diabetic animals.
Studies on transhepatic insulin absorption
Authors: Zingg W. , Rappaport A. M. , Leibel B. S.
Published: April 2011

The intraperitoneal administration of insulin has been recommended because it was found to effectively control the plasma glucose level. Several authors have suggested that intraperitoneal insulin administration may be more "physiological" and therefore preferable because the insulin is absorbed into the portal venous system without, however, identifying the exact pathways. The possibility that insulin is absorbed through the surface of the liver was investigated in rats. The results show that insulin is absorbed rapidly by this route, but the effect on glucose modulation is similar to that of insulin given by other routes. In contrast, the effect on glucose modulation was delayed following insulin administration into the lower peritoneal cavity with exclusion of the liver.
Amygdaloid kindling in aiioxan-diabetic rats
Authors: Mello Luiz E. A. M. , Cavalheiro Esper A.
Published: April 2011

Wistar rats, made diabetic by intravenous administration of alloxan, 40 mg/kg, were submitted to amygdala kindling. The EEG and behavioral responses elicited by stimulating the amygdala nuclei in these animals were compared with those observed in control rats. Alloxan-treated rats required more stimulation to kindle, had increased duration of afterdischarges (AD), presented intense interictal spiking, and exhibited greater number of wet-dog shakes than controls. Although the AD threshold was not different between control and experimental rats, the above results seem to indicate an increase in the local epileptic susceptibility represented by longer ADs. On the other hand, this increased local discharge seems to be unable to access the generalization mechanism, which can be verified by the increased kindling rate. Hyperosmolarity, pH alterations, or other generalized metabolic changes frequently associated with diabetes could be implicated in these results.
Inhibition of water–sodium intestinal absorption by an atrial extract
Authors: Seeber A. Martïnez , Vidal N. A. , Carchio S. M. , Karara A. L.
Published: April 2011

The rat atrium contains a diuretic and natriuretic factor which appears to inhibit the sodium reabsorption in the kidney tubules. We observed, in rats, that our atrial extract possesses a potent diuretic and natriuretie effect that was accompanied by an increased dextrose excretion. Similarly, extracts of rat atria, but not of ventricles, reduced intestinal absorption of water, sodium, and dextrose. The omission of sodium or dextrose in the perfusion fluid annulled this effect. These data suggest that the substance inhibiting the intestinal absorption of water and solutes is probably atrial natriuretie factor and that it acts on the sodium–dextrose cotransport mechanism.
Comparative effects of the ionophore A23187 on the mechanical responses of muscle in normal Pietrain pigs and pigs with malignant hyperthermia
Authors: Reiss G. , Monin G. , Lauer C.
Published: April 2011

Since increased intracellular Ca2+ is believed to be the main factor causing skeletal muscle contracture in human and porcine malignant hyperthermia, the potential effects of the ionophore A23187, which enhances intracytoplasmic Ca2+, were investigated in Pietrain pig muscles. These effects were compared with those of caffeine, known to induce dose-dependent contracture in vitro in isolated muscle from human subjects with malignant hyperthermia. For this purpose, the mechanical and biochemical actions of caffeine and A23187 were tested in intercostal muscle biopsies from 10 normal pigs and 10 with malignant hyperthermia. The results show that A23187 allowed very clear differentiation between the muscles of normal and pathological animals. In view of the wide spectrum of drug sensitivity characterizing subjects with malignant hyperthermia, it is suggested that exposure to A23187 be added to the halothane and caffeine tests currently used to detect this disease.
Inhibitory actions of a series of Ca2+ channel antagonists against agonist and K+ depolarization induced responses in smooth muscle: an assessment of selectivity of action
Authors: Yousif F. B. , Triggle D. J.
Published: April 2011

The inhibitory effects of the Ca2+ channel antagonists D-600, diltiazem, nifedipine and seven 1,4-dihydropyridine analogs of nifedipine against 80 mM K+ depolarization induced responses in guinea pig trachea, parenchyma, and pulmonary artery and rat renal and mesenteric artery preparations were determined. Together with similar data previously obtained for guinea pig ileum and bladder, these data permitted an assessment of tissue selectivity of action in smooth muscles of a series of Ca2+ channel antagonists under constant conditions (saline composition) and an identical challenge (K+ depolarization). Very similar rank orders of activity were expressed in all tissues suggesting that the same basic structure–activity relationship operates. However, the series of antagonists were significantly less active in respiratory smooth muscle than in other visceral or vascular smooth muscles. pA2 values for a series of 1,4-dihydropyridine antagonists measured in guinea pig taenia coli against Ca2+-induced responses in K+-depolarizing media correlated with mean inhibitory concentration values against K+-induced responses, suggesting that the latter were an appropriate measure of antagonist potency. pA2 values measured for nifedipine, D-600, and diltiazem against Ca2+-induced responses in taenia coli in the presence of a depolarizing K+ saline, or methylfurmethide, histamine, or 5-hydroxytryptamine did not differ, suggesting that the same channels were activated regardless of stimulant.
Neurochemical effects of choline supplementation
Authors: Wecker Lynn
Published: April 2011

Whether or not the brain can use supplemental choline to enhance the synthesis of acetylcholine (ACh) is an important consideration for assessing the merits of using choline or phosphatidylcholine (lecithin) for the treatment of neuropsychiatric disorders postulated to involve hypocholinergic activity. While it is well documented that administered choline is incorporated into ACh, the ability of supplemental choline to increase the synthesis and release of ACh has been questionable. Studies in my laboratory have demonstrated that acute or chronic choline supplementation does not, by itself, enhance the levels of ACh in brain under normal biochemical and physiological conditions. However, supplemental choline prevents the depletion of ACh in brain induced by numerous pharmacological agents that increase the firing of cholinergic neurons. Since the levels of free choline in brains from supplemented rats were not different from controls prior to drug challenge, evidence suggested that the observed effects of choline were mediated by alterations in the mobilization of choline from choline-containing compounds. Studies investigating the release of choline from brain indicated that more choline was released per unit time in tissues from choline-supplemented rats than from controls. In addition, brain tissue from choline-supplemented rats had increased concentrations of total lipid phosphorus as compared with controls. Hence, although choline supplementation does not alter the levels of ACh in brain under normal conditions, it does appear to support ACh synthesis during drug-induced increases in neuronal activity, an effect most likely mediated by alterations in the metabolism of choline-containing phospholipids.
Blood volume, the venous system, preload, and cardiac output
Authors: Greenway Clive V. , Lautt W. Wayne
Published: April 2011

Cardiac output is determined by heart rate, by contractility (maximum systolic elastance, Emax) and afterload, and by diastolic ventricular compliance and preload. These relationships are illustrated using the pressure–volume loop. Diastolic compliance and Emax place limits determined by the heart within which the pressure–volume loop must lie. End-diastolic and end-systolic pressures and hence the exact position of the loop within these limits are determined by the peripheral circulation. In the presence of minimal sympathetic tone, some 60% of total blood volume is hemodynamically inactive and constitutes a blood volume reserve (the unstressed volume). The remainder of the blood volume (the stressed volume) and the compliance of the venous system determine the venous pressure. This venous pressure together with venous resistance determines venous return, right atrial pressure, cardiac preload, and hence cardiac output. Venoconstriction causes conversion of unstressed volume to the stressed volume, the blood volume reserve is converted into hemodynamically active blood volume. After hemorrhage this replaces the lost stressed volume, while in other situations where total blood volume is not reduced, it allows a sustained increase in cardiac output. The major blood volume reserve is in the splanchnic bed: the liver and intestine, and in animals but not man, the spleen. A major unsolved problem is how the conversion of unstressed volume to stressed volume by venoconstriction is reflexly controlled.
Mapping of ventricular tachycardia induced by thoracic neural stimulation in dogs
Authors: Cardinal René , Savard Pierre , Armour J. Andrew , Nadeau Réginald , Carson D. Leigh , LeBlanc A. Robert
Published: April 2011

To investigate ventricular tachycardias produced in healthy canine myocardium by stimulation of sympathetic ganglia or cardiac nerves, we simultaneously recorded a surface ECG and 63 ventricular electrograms in anesthetized open-chest dogs. Isochronal and isopotential maps were generated off-line by computer. Ventricular tachycardia with uniform beat-to-beat morphology was induced in 13 or 22 dogs by electrical stimulation of the left stellate ganglion (five experiments), the left middle cervical ganglion (four experiments), the left caudal pole cardiopulmonary nerve (two experiments), or the ventrolateral cardiac nerve (eight experiments). It was not inducible by stimulation of the right-sided major cardiopulmonary nerves or ganglia. In most instances the earliest measured electrical excitation occurred on the posterior aspect of the ventricles. Isochronal maps demonstrated a radial spread of the impulse away from the area of earliest excitation. Changes in the region of earliest excitation and (or) activation pattern were accompanied by changes in QRS morphology. The potential gradients measured between areas displaying positive and negative T waves on the anterior and left lateral aspects of the ventricles were significantly increased by ventrolateral cardiac nerve stimulation. However, the ventricular regions where these potential gradients existed differed from the regions of earliest excitation during ventricular tachycardia. These results demonstrate that the thoracic autonomic nervous system can induce repetitive ventricular excitation originating from consistent loci.
Temporal relationships between biotransformation, detoxication, and chlordecone potentiation of chloroform-induced hepatotoxicity
Authors: Hewitt L. Arthur , Caillé Gilles , Plaa Gabriel L.
Published: April 2011

Exposure to chlordecone (CD, Kepone) is known to increase the hepatotoxicity of chloroform (CHCl3) in rats. A time-course analysis was conducted relating several indices of biotransformation capacity with the ability of CD to potentiate CHCl3-induced hepatotoxicity. Male Sprague–Dawley rats were given a single administration of corn oil alone or CD (50 mg/kg, po) dissolved in corn oil. At 2, 4, 8, 16, 20, 24, or 32 days posttreatment, groups of rats were killed and their livers were analyzed for (i) cytochrome P-450, NADPH-dependent cytochrome c reductase, cytochrome b5 and glutathione content or (ii) in vitro irreversible binding of 14CHCl3-derived radiolabel to microsomal protein. Similarly treated rats were challenged (2–32 days posttreatment) with CHCl3 (0.5 mL/kg po); 24 h later, liver damage was assessed by plasma alanine aminotransferase (ALT), plasma ornithine carbamyl transferase (OCT), plasma bilirubin, and hepatic glucose-6-phosphatase. CD potentiation was maximal 2 days posttreatment; and enhanced susceptibility to CHCl3 persisted up to 20–24 days post-CD treatment. In a parallel study animals treated with chlordecone were killed 8, 16, 20, 24, or 32 days later. Blood, kidney, liver, and adipose tissue samples were taken and analyzed for chlordecone content. The results suggest that a general temporal correlation exists between biotransformation rate (microsomal 14C binding), chlordecone content, and the severity of liver injury; the other parameters monitored do not appear to relate directly to the potentiation.
Role of calcium channel in postvagal potentiation of contraction as evident from the effects of Mn2+, La3+, D-600, and deoxycholate on isolated guinea pig atria–vagus nerve preparation
Authors: Tripathi Onkar N. , Mehrotra M. , Dhawan B. N.
Published: April 2011

The role of the calcium channel in the first large contraction (postvagal potentiation, PVP) of the atria at the end of the inhibitory phase of its response (IPR) to vagal stimulation has been investigated by studying the effects of agents acting on the calcium channel (e.g., Ca2+, Mn2+, La3+, and D-600) or sarcoplasmic reticulum (SR) (e.g., deoxycholate (DOC)). IPR was potentiated by high [Ca2+]o (3–16 mM) and also by the calcium channel blockers, Mn2+ (1 μM–0.5 mM), La3+ (0.1 μM–0.5 mM), D-600 (1.0–10 μM), and DOC (1 μM–0.5 mM). PVP was also potentiated by enhanced [Ca2+]o, but the PVP ratio, which employs a correction for the simultaneous changes in the force of spontaneous contraction was inhibited. This indicated greater potentiation of contractility during spontaneous activity by Ca2+ than during PVP. Mn2+, La3+, and D-600 and even DOC in the above concentrations inhibited PVP but increased the PVP ratio. High concentrations of DOC (>1 mM), which disrupt SR, strongly inhibited PVP. It is concluded that the calcium channel plays a more prominent role in spontaneous contractions than in PVP in guinea pig atria. PVP is suggested to be generated by excessive triggered release of Ca2+ from SR leading to a marked increase in [Ca2+]i. The calcium channel and the calcium trapped in the glycocalyx also play significant roles in PVP.
Inhibition of Zn2+-induced potentiation of twitch tension by Ni2+ in frog muscle
Authors: Oba Toshiharu , Hotta Ken
Published: April 2011

Effect of Ni2+ on Zn2+-induced potentiation of twitch tension was studied electrophysiologically in the toe muscle fibers of Rana catesbeiana. The major findings of this investigation are as follows. When 2 mM Ni2+ was applied to fibers in a normal Ringer's solution containing 50 μM Zn2+ (Zn2+ solution), the Zn2+-potentiated twitch tension decreased remarkably to about one-third of that before Ni2+ treatment. This concentration of Ni2+ caused a 23% decrease in the duration of action potential which had been prolonged by Zn2+ (6.61–5.09 ms). Ni2+ (2 mM) added to normal Ringer's solution led to increases of about 30 and 42% in twitch tension and in the duration of action potential, respectively. A slight increase in the mechanical threshold was induced by 2 mM Ni2+. The inhibitory action of Ni2+ on the twitch tension in Zn2+ solution was larger than that in the case of tetanus tension. Diltiazem (40 μM), aCa2+ channel blocker, did not inhibit the twitch tension potentiated in Zn2+ solution. These results suggest that the decrease in Zn2+-potentiated twitch tension by Ni2+ may possibly derive from impairment of the propagation of action potential along the T tubules.
Differential effects of methylmercuric chloride and mercuric chloride on the L-glutamate and potassium evoked release of [3H]dopamine from mouse striatal slices
Authors: McKay S. J. , Reynolds J. N. , Racz W. J.
Published: April 2011

The effects of CH3HgCl and HgCl2 on the evoked release of 3H from mouse striatal slices prelabelled with [3H]dopamine have been examined. CH3HgCl (10 μM) was observed to increase the L-glutamate-evoked release of [3H]dopamine, while HgCl2 (10 μM) had no effect. In contrast, CH3HgCl at concentrations up to 100 μM had no effect on the 25 mM K+-stimulated release of [3H]dopamine, whereas HgCl2 (100 μM) significantly reduced the 25 mM K+-stimulated release of [3H]dopamine. Thus CH3HgCl and HgCl2 have differential effects on the L-glutamate- and K+-stimulated release of [3H]dopamine from mouse striatal slices, suggesting that these compounds may have different sites and (or) mechanisms of action in altering neurotransmitter release. It is suggested that CH3HgCl may act predominantly at intracellular sites or at the level of the L-glutamate receptor, whereas the major site of action of HgCl2 may be the voltage-operated calcium channel.
Branching characteristics of human coronary arteries
Authors: Zamir M. , Chee H.
Published: April 2011

Branching angles and branch diameters were measured in a total of 850 arterial junctions in the coronary networks of two human hearts. Comparison is made with similar data obtained previously from the coronary networks of rats, and with what is considered to be optimum on theoretical grounds. It is concluded that the branching characteristics of the human coronary arteries are closer to the theroretical optimum than those of the coronary networks of rats. While the human data exhibit some departure from optimality and a good amount of scatter, these are well within levels observed elsewhere in the cardiovascular systems of man and animals, and considerably better than those found in the coronary networks of rats. The departure from optimality, in terms of physiological cost to the system, is within 5% for most data points.
Effects of triiodothyronine and carnitine therapy on myocardial dysfunction in diabetic rats
Authors: Tahiliani Arun G. , McNeill John H.
Published: April 2011

Streptozotocin-diabetic rats were treated with a combination of triiodothyronine and carnitine for 6 weeks. These compounds were used as they are known to correct the diabetes-induced depression of cardiac myosin ATPase and sarcoplasmic reticular (SR) calcium uptake, respectively. Myocardial performance, which was assessed using the working heart preparation, revealed a depression of function in untreated diabetics when compared with controls at most left atrial filling pressures. Hearts from diabetic rats treated with the combination exhibited depression at only the higher filling pressures as compared with untreated or treated controls. The results suggest that functional alterations occurring as a result of diabetes cannot be accounted for by the depression of cardiac myosin ATPase and SR calcium uptake alone.
Semiautomated analysis of ethanol and acetate in human plasma by head space gas chromatography
Authors: Giles H. G. , Meggiorini S. , Vidins E. I.
Published: April 2011

Plasma samples (0.5 mL) were analyzed for ethanol and acetate by head space gas chromatography using a Porapak QS® column (80–100 mesh). Acetate was esterified to methyl acetate simply by the addition of acidified methanol. The analytical ranges were 1.61–103 and 0.05–1.9 mM for ethanol and acetate, respectively. The within-run coefficients of variation did not exceed 4.7% for acetate and 2.7% for ethanol. After the oral administration of ethanol to two healthy human subjects, the concentration versus time profiles of plasma ethanol and acetate were determined. Acetate concentrations (0.4–0.9 mM) remained quite constant while ethanol was being metabolized and appeared not to be affected by the concentration of ethanol in the range 3–18 mM. The advantages of the method are speed and simplicity.
Metabolism and disposition of N-(2-cyanoethyl)amphetamine (fenproporex) and amphetamine: study in the rat brain
Authors: Coutts R. T. , Nazarali A. J. , Baker G. B. , Pasutto F. M.
Published: April 2011

N-(2-Cyanoethyl)amphetamine (fenproporex, CE-AM) is a clinically used anorexiant claimed to be devoid of the stimulant properties associated with amphetamine (AM). This claim was inconsistent with preliminary studies conducted in our laboratories which indicated that CE-AM is metabolically dealkylated to AM to a considerable extent in the rat. Concentration–time profiles of CE-AM and its metabolites AM and 4-hydroxyamphetamine (4-OH-AM) in the rat brain were constructed after administration of CE-AM. Analyses of CE-AM, AM, and 4-OH-AM were performed by gas chromatography with electron-capture detection using pentafluorobenzoyl chloride (under aqueous conditions) as the derivatizing reagent. The half-life (t1/2) and the maximum concentration (Cmax) of AM after administration of CE-AM were calculated to be 2.04 and 0.56 times the respective t1/2 and Cmax obtained after an equimolar dose of AM. Significant differences in the profiles of 4-OH-AM were also observed. The Cmax of 4-OH-AM in rat brain after administration of CE-AM was nearly 4 times higher and the tmax (time at which concentration is maximum) 4 times lower than the respective Cmax and tmax values of 4-OH-AM observed after an equimolar dose of AM.
Involvement of intramural prostaglandin E2 in prenatal patency of the lamb ductus arteriosus
Authors: Coceani Flavio , Huhtanen Dayle , Hamilton Nancy C. , Bishai Isis , Olley Peter M.
Published: April 2011

Release of prostaglandin E2 (PGE2) was studied in isolated ductus arteriosus preparations from immature (103 or 104 days gestation; term, 147 days) and near-term fetal lambs. Mature preparations produced measurable amounts of the compound in most cases and the release rate was 19 ± 2 pg/(100 mg wet weight∙min) at a [Formula: see text] of 3–8 Torr (1 Torr = 133.3 Pa). PGE2 release increased with the [Formula: see text] of the medium, peak values (about 125 pg/(100 mg∙min)) being attained at 106–276 Torr when the oxygen-induced contraction was still submaximal. Experiments in which tissues were either contracted with excess potassium or relaxed with CO proved that PGE2 formation is independent from the contractile state. PGE2 was also released from ductus preparations lacking the adventitia, the intima, or both; however, release values were maximal when the adventitia was preserved. The magnitude of the intrinsic tone in these stripped preparations was inversely related to the rate of PGE2 formation. Reduced glutathione increased PGE2 release from the mature ductus, whole or stripped, and also relaxed hypoxic preparations; both effects were reversed by concomitant treatment with indomethacin. PGE2 synthesis tended to be greater in the immature than the mature ductus, maximal values (115 ± 27 pg/(100 mg∙min)) being observed at 6–8 Torr. We conclude that the ductus arteriosus is endowed with an enzyme system for the synthesis of PGE2 whose function accords with an effector role of the compound in the regulation of tone. These findings, together with the potent relaxation exerted by PGE2 at low [Formula: see text], indicate that the locally generated prostaglandin is well suited for keeping the ductus patent in the fetus.
Behavioral effect of cholecystokinin octapeptide in vagotomized rats
Authors: Itoh Shinji , Katsuura Goro
Published: April 2011

Cholecystokinin octapeptide (CCK-8) was administered intracerebroventricularly (icv) or subcutaneously (sc) into subdiaphragmatically vagotomized and sham-operated rats, and the behavioral effects were quantified by an open-field test. Intracerebroventricularly injection of CCK-8 decreased locomotion and rearing to the same extent in both vagotomized and sham-operated rats, while sc injection produced behavioral changes only in sham-operated rats but not in vagotomized ones. The results indicate that CCK-8 affects both central and peripheral receptors, and the vagal nerve may be the major pathway causing behavioral effects from the visceral organs to the brain.
Practical aspects of dietary management of hypertension: compliance
Authors: Dunbar Jacqueline
Published: April 2011

This paper addresses compliance issues that arise in the implementation of weight loss and other therapeutic diets prescribed for the individual with hypertension. Dietary compliance poses a significant problem. Studies suggest that dropout rates in both self-help and other weight loss programs range from 50 to 70% within 1–2 years. Further, just 50% of persons can be expected to comply with diets for cardiovascular disease. Assessment of adherence is confounded by the lack of precise measures that reflect adherence over time. Measures in general use include daily diaries, urinary chloride dip sticks, multiple 24-h or overnight urinary sodium, analysis of food samples, as well as 24-h recall and food histories. When poor compliance has been identified, it has been associated with a variety of factors. These include multicomponent regimens, conflicting lifestyle habits, skill in identifying and (or) preparing appropriate foods, the cost: benefit ratio of compliance, and social support. Limited investigation has been undertaken to directly improve compliance to diet. However, such strategies as tailoring, goal setting, self-monitoring, stimulus control, social support, cognitive restructuring, and a consistent approach between the care providers show promise.
Proteins and amino acids: effects on the sympathetic nervous system and blood pressure regulation
Authors: Anderson G. Harvey
Published: April 2011

Many functions of the brain and the sympathetic adrenal system are influenced by those amino acids that exert precursor control over neurotransmitter synthesis. One of the functions affected is regulation of blood pressure. Therefore, the purpose of this review is to describe how food proteins and amino acids affect the synthesis of neurotransmitters and their regulation of blood pressure.
The relationship between motor activity and transmural potential difference in the guinea pig intestine in vitro: is there a neural link?
Authors: Greenwood Beverley , Diamant Stephanie , Davison J. S.
Published: April 2011

The aim of the experiments was to examine, in vitro, the role of the enteric nervous system in the relationship between motor activity and transmural potential difference (PD) in the guinea pig jejunum and colon using the nerve blocking agents tetrodotoxin (TTX) and aconitine. Histological data showed that perfusion of the intestinal segments with gassed Hepes solution was essential for the maintenance of transmural PD. Disruption of the mucosa was associated with a loss of spontaneous fluctuations in transmural PD without any loss of spontaneous motor activity. Under spontaneous conditions, a neural pathway exists linking jejunal and colonic motility with transmural PD. However, in some cases a mechanical link was also apparent, as an attenuated TTX and aconitine–resistant component.
Comparison of two methods of altering blood pressures for assessing neonatal cerebral blood flow autoregulation
Authors: Ong B. Y. , MacIntyre C. , Bose D. , Palahniuk R. J.
Published: April 2011

The cerebral blood flow of newborn lambs at reduced and elevated arterial blood pressures, induced by intravenous infusion of sodium nitroprusside and phenylephrine hydrochloride as well as blood withdrawal and reinfusion, were compared. Both blood withdrawal and sodium nitroprusside infusion reduced mean arterial pressure from 83 to 60 mmHg (1 mmHg = 133 Pa). Reinfusion of blood increased arterial pressure to 94 mmHg. Phenylephrine hydrochloride infusion increased arterial pressure to 102 mmHg. The cerebral blood flows at corresponding arterial pressures were similar (coefficient of correlation = 0.88, P < 0.01). Cerebral blood flow before and after infusion of phenylephrine hydrochloride and sodium nitroprusside into the brain via the carotid artery did not change. The results indicate that blood-borne phenylephrine hydrochloride and sodium nitroprusside, in concentrations that would alter arterial blood pressure significantly from its resting level, do not change cerebral blood flow directly.