bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptidergic inputs to sympathetic preganglionic neurons
Authors: Krukoff Teresa L.
Published: April 2011

This paper presents data showing that the sympathetic autonomic areas of the cat thoracolumbar spinal cord contain nerve terminals and fibres with immunoreactivity for at least seven neuropeptides. The distribution in the intermediolateral cell column of the terminals and fibres which contain enkephalin-, neuropeptide Y-, neurotensin-, substance P-, and neurophysin II-like immunoreactivity (ENK, NPY, NT, SP, and NP2, respectively) suggests that these peptides are involved in more generalized functions of the autonomic nervous system. On the other hand, peaks in density of immunoreactivity at certain levels suggest that different levels of influence of sympathetic preganglionic neurons by the various peptides may occur along the length of the thoracolumbar cord. The distribution of terminals and fibres containing somatostatin- and oxytocin-like immunoreactivity (SS and OXY) suggests that these peptides may be part of specific pathways to particular sympathetic preganglionic neurons. The possible sources of the terminals and fibres containing ENK, NPY, NT, SS, and SP include the spinal cord and supraspinal areas, whereas the source of these structrues with OXY and NP2 is most likely supraspinal. The data suggest that coexistence of peptides and interactions between structures containing different neuropeptides occur in the spinal autonomic areas. It is speculated that neuropeptides have an important role to play in the regulation of the cardiovascular division of the autonomic nervous system.
Responses of vasoactive hormones in congestive cardiac failure
Authors: Johnston C. I. , Arnolda L. F. , Tsunoda K. , Phillips P. A. , Hodsman G. P.
Published: April 2011

Congestive cardiac failure causes activation of various neurohumoral responses that increase total peripheral resistance and promote salt and water retention. These effects increase blood pressure and organ perfusion in the short term, but ultimately cause further cardiac decompensation by increasing ventricular afterload and cardiac work. The role of the renin–angiotensin–aldosterone system and the catecholamines is partially understood, and blockade of these systems as a treatment of heart failure is now established. The role of vasopressin in heart failure is more controversial, but there is now compelling evidence that vasopressin may have important vasoconstrictor actions in addition to its fluid retaining properties. Atrial natriuretic factor is a newly described cardiac hormone released from the atrium. Atrial natriuretic factor causes natriuresis, diuresis, vasodilatation, suppression of thirst, and suppression of both renin and aldosterone. These actions largely counteract the effects of the renin–angiotensin system and vasopressin. Plasma atrial natriuretic factor has been reported to be markedly elevated in human and experimental heart failure, and may act to limit the neurohumoral response to reduced cardiac output. This review summarizes our understanding of the vasoactive hormones and reports experimental evidence supporting a pathophysiological role for vasopressin and atrial natriuretic factor in congestive cardiac failure.
Sodium restriction can delay the return of hypertension in patients previously well-controlled on drug therapy
Authors: Morgan Trefor , Anderson Adrianne
Published: April 2011

Sodium restriction can reduce blood pressure in hypertensive patients. The present study indicates that if hypertension is well controlled then the reemergence of hypertension can be decreased by the use of a reduced sodium intake. The present paper demonstrates that in such patients on a normal salt diet, 90% become hypertensive within 6 months while only 40% of people on a reduced sodium diet become hypertensive. It is proposed that a high sodium intake activates a number of amplifiers that causes a shift of the dose–response curve to sodium to the left and if not prevented or interrupted leads to the development of hypertension.
Calcium channels and excitation–contraction coupling in cardiac cells. I. Two components of contraction in guinea-pig papillary muscle
Authors: Honoré E. , Adamantidis M. M. , Dupuis B. A. , Challice C. E. , Guilbault P.
Published: April 2011

Biphasic contractions have been obtained in guinea-pig papillary muscle by inducing partial depolarization in K+-rich solution (17 mM) containing 0.3 μM isoproterenol; whereas in guinea-pig atria, the same conditions led to monophasic contractions corresponding to the first component of contraction in papillary muscle. The relationships between the amplitude of the two components of the biphasic contraction and the resting membrane potential were sigmoidal curves. The first component of contraction was inactivated for membrane potentials less positive than those for the second component. In Na+-low solution (25 mM), biphasic contraction became monophasic subsequent to the loss of the second component, but tetraethylammonium unmasked the second component of contraction. The relationship between the amplitude of the first component of contraction and the logarithm of extracellular Ca2+ concentration was complex, whereas for the second component it was linear. When Ca2+ ions were replaced by Sr2+ ions, only the second component of contraction was observed. It is suggested that the first component of contraction may be triggered by a Ca2+ release from sarcoplasmic reticulum, induced by the fast inward Ca2+ current and (or) by the depolarization. The second component of contraction may be due to a direct activation of contractile proteins by Ca2+ entering the cell along with the slow inward Ca2+ current and diffusing through the sarcoplasm. These results do not exclude the existence of a third "tonic" component, which could possibly be mixed with the second component of contraction.
Endothelial cell morphometry near branch junctions of rabbit aortae
Authors: Kratky Ralph G. , Roach Margot R.
Published: April 2011

Endothelial cell morphometric data were gathered from corrosion casts of the aorta and its branches of six New Zealand white rabbits weighing 2–3 kg. The endothelial cell outlines were ditigized to provide cell orientation index (COI) from the equation COI = 2Mg/2Ml−1, where 2Ms and 2Ml are the second moments of area about short and lone axes of the cell. The COI varies from zero to infinity. The former occurs when cells are symmetrical (e.g., circular) since 2Ms = 2Ml and the latter occurs for a straight line. Large values of COI were found distal to intercostals, lumbars, and the aortorenal junction, and probably reflect relatively stable high shear regions. Values close to zero occur on the flow divider where the shear stress approaches zero. Other values were less predictable and we concluded that while the long axis of the cell appears to indicate flow direction, the shape of the cell does not appear to be a reliable indicator of either tensile forces or shear stress acting in it, but probably reflects a combination of the two.
Muscarinic receptors on nerves and muscles in opossum esophagus muscularis mucosa
Authors: Daniel E. E. , Jury J. , Bowker P.
Published: April 2011

The muscarinic receptors of muscularis mucosa have some recognition properties that suggest they resemble receptors of the M1 sybtype. The nerves of these tissues also contain muscarinic receptors which inhibit tonic contractions caused by release of a substance-P-like material by field stimulation. These receptors also appear to be M1 in type as they are maximally activated by McNeil A343 as well as by carbachol (pD2, 5.5 and 7.5, respectively). They are also inhibited by pirenzepine, as well as by atropine (negative logarithms of the required dose for 50% inhibition or potentiation, 6.6–6.7 compared with 8.2–8.3). Hexahydrosiladifenidol, an antagonist selective for M2 receptors of guinea pig ileum, had a low (~7.1) pA2 value for antagonism of both agonists in smooth muscle in this tissue. However, it was closer to atropine in potency with respect to potentiating tonic responses to field stimulation or to inhibiting phasic responses to field stimulation than it was to antagonizing smooth muscle contractions. Thus, atropine was about 40 times more potent than pirenzepine and 2–5 times more potent than hexahydrosilafenidol. There were some quantitative differences in the effectiveness of these three antagonists in blocking the phasic (acetylcholine-mediated) response to field stimulation. Atropine was 70–100 times more potent than pirenzepine and 8–25 times more potent than hexahydrosiladifenidol. This greater potency difference for inhibition of phasic contractions compared with potentiation of tonic contractions was discussed. This tissue appears to be one of the first smooth muscles in which both nerves and muscles contain muscarinic receptors with some recognition properties resembling those of the M1 subtype.
Binding of the hydrophilic β-adrenergic antagonist [3H]CGP-12177 to cardiac tissue slices: characterization and ontogenetic studies in dogs
Authors: Haddad C. , Wilkinson M. , Roeder L. M. , Tildon J. T. , Armour J. A.
Published: April 2011

A new technique was developed to characterize the binding of a hydrophilic β-adrenergic antagonist, [3H]CGP-12177, to 1-mm thick slices of canine cardiac tissue. This technique was used to quantify the density (Bmax) and the affinity (Kd) of these receptors in the right ventricular conus (RVC) and the left ventricle (LV) at day 1 to 6 weeks of age, and in the adult. Binding was found to be reversible, saturable, stereospecific, of high affinity, and thermolabile. There was an increase in the density of β-adrenergic receptors between day 1 (Bmax = 2.2 ± 0.3 fmol/mg tissue in RVC and 2.9 ± 0.8 fmol/mg tissue in the LV) and 2 weeks of age postnatally, after which it remained constant until 6 weeks of age (Bmax = 7.5 ± 0.4 and 6.8 ± 0.9 fmol/mg tissue in RVC and LV, respectively); however, by 6 weeks of age it had not reached adult levels (10.3 ± 1.0 fmol/mg tissue). The affinity of these receptors did not change between early neonatal life (Kd = 1.3 ± 0.4 nM) and adulthood (Kd = 1.4 ± 0.2 nM). The density of β-adrenergic receptors in the RVC was similar to that in the LV. This new method of quantifying β-adrenergic receptors in cardiac tissue is simple and fast, and requires minimal tissue handling. It proved to be useful in studying the development of cardiac β-adrenergic receptors with age.
Inhibition of neuromuscular transmission in the guinea-pig saphenous artery by atriopeptrin II
Authors: MacKay M. J. , Cheung D. W.
Published: April 2011

In the guinea-pig saphenous artery, stimulation of perivascular nerves elicited contraction and two types of synaptic potentials: the excitatory junction potential and the slow depolarization. The synaptic potentials were inhibited by atriopeptin II but not by sodium nitroprusside. Exogenous noradrenaline induced membrane depolarization and contraction, and both sodium nitroprusside and atriopeptin II inhibited the contraction but not the depolarization. These results suggest that atriopeptin II has an inhibitory effect both presynaptically at the nerve terminals and postsynaptically on the vascular smooth muscle cells.
Adrenergic and osmotic responses to atrial natriuretic peptide and angiotensin II in the duck (Anas platyrhynchos)
Authors: Wilson John X.
Published: April 2011

There is evidence that analogues of atrial natriuretic peptide (ANP) and angiotensin II (ANG II) occur in birds. The present experiments studied the adrenergic and osmoregulatory responses to synthetic ANP and ANG II in salt-loaded ducks (Anas platyrhynchos). Excretion of water and salt through the nasal salt glands was abolished by ANG II. This extrarenal, salt-retaining effect of ANG II was not altered by ANP. However, ANP did augment the diuretic response to ANG II. ANP also potentiated the stimulatory effect of ANG II on plasma norepinephrine. The data are consistent with physiological roles for native analogues of ANP and ANG II in adrenergic and osmotic regulation in the duck.
Gallbladder pressure, compliance, and hysteresis during cyclic volume change
Authors: Cole M. J. , Shaffer E. A. , Scott R. B.
Published: April 2011

The gallbladder has both storage and contractile properties, but its pressure–volume characteristics have not been fully described. We studied gallbladder pressure, compliance, stress relaxation, and the work performed during infusion–withdrawal of fixed volumes of bile at increments of base-line volume under halothane anesthesia in 13 dogs. Two cannulae were inserted in the gallbladder fundus: one for cyclic infusion–withdrawal of bile, and one for pressure monitoring. Following ligation of the cystic duct, the gallbladder was fully aspirated and then filled to successive predetermined base-line volumes (15, 20, 25, 30, or 35 mL). At each base-line volume, 5 mL of bile was infused and withdrawn at 2.47 mL/min. Studies were performed under basal conditions and with cholecystokinin octapeptide (CCK) infusion (10 or 30 ng∙kg−1∙h−1 iv). Pressure was measured at base-line, after infusion, and after withdrawal. Compliance during infusion (ΔV/ΔP) was calculated for each cycle. Stress relaxation was defined as the difference between base-line pressure and any reduction in pressure after withdrawal. Hysteresis, the difference between work of infusion and work of withdrawal, was calculated. The results were such that base-line, end-infusion, and end-withdrawal pressures; work of infusion, work of withdrawal, and hysteresis; and stress relaxation all increased significantly with increases in the predetermined base-line volumes (p < 0.001). Compliance decreased significantly (p < 0.001) with increasing base-line volume. CCK at 10 ng∙kg−1∙h−1 iv had no effect, but infusion of CCK at 30 ng∙kg−1∙h−1 significantly (p < 0.05) increased pressure and work, decreased compliance, and increased stress relaxation compared with controls. Thus, with increasing resting volumes of bile, the gallbladder (1) exhibits increased intraluminal pressure and decreased compliance in response to further filling, but (2) accommodates to increased distension by stress relaxation. In response to CCK there is a decrease in compliance that promotes emptying.
The influence of α-fluoromethylhistidine on the regional brain histamine and plasma corticosterone levels in aging
Authors: Mazurkiewicz-Kwilecki I. , Nsonwah Simon
Published: April 2011

α-Fluoromethylhistidine, a histidine decarboxylase inhibitor, induced a significant depletion in the hypothalamic, midbrain, and cortical brain histamine amounts in 12- and 3-month-old rats. In all three brain regions the most evident depletion occurred 2 h after treatment. In both groups of rats midbrain histamine levels returned to control values 6 h after treatment; however, hypothalamic histamine depletion was still significant and more evident in the old than in the young animals. Cortical brain histamine also remained significantly depleted in old rats, but returned to control values in young animals 6 h after α-fluoromethylhistidine treatment. These results suggest that old rats show a slower rate of new histamine synthesis in the cortex and hypothalamus. Regional brain histamine depletion was associated with a very significant decrease in plasma corticosterone levels, which indicates that brain histamine–corticosterone interactions do occur.
Interactions of cholecystokinin, β-endorphin, and their antagonists on passive avoidance behavior in rats
Authors: Itoh Shinji , Katsuura Goro , Takashima Akira
Published: April 2011

The effects of cholecystokinin octapeptide (CCK-8), cholecystokinin tetrapeptide amide (CCK-4), β-endorphin, proglumide, and naloxone on passive avoidance behavior were studied in rats. Intracerebroventricular (i.c. v.) injection of β-endorphin (1–10 μg) had no significant influence on the latency of the avoidance response in intact rats. Also, β-endorphin (0.05–5 μg, i.c. v.) did not affect the response in rats treated with electroconvulsive shock (ECS). The preventive effect of CCK-8 (0.1–1.0 μg, i.c.v.) on ECS-induced amnesia was partly antagonized by β-endorphin (0.05–10 μg, i.c.v.). Intraperitoneal (i.p.) injection of naloxone (1–10 mg/kg) could not prevent ECS-induced amnesia, but continuous subcutaneous infusion of this drug (2 mg/day, 7 days) completely abolished the amnesia. Naloxone (1 and 10 mg/kg, i.p.) also partly antagonized amnesia induced by proglumide (1 and 10 μg, i.c.v.) and prevented it when induced by CCK-4 (5 and 10 μg, i.c.v.). The results indicate the facilitating action of naloxone and the inhibitory effect of β-endorphin on memory, suggesting that the endogenous opiate systems are involved in some way in the memory processes.
Enhancement of [3H]DAGO1 binding to rat brain by low concentrations of monovalent cations
Authors: Bolger Gordon T. , Marcus Kendall A. , Thibou Ronald , Skolnick Phil , Weissman Ben Avi
Published: April 2011

The effects of mono- and di-valent cations and the nonhydrolyzable guanyl nucleotide derivative 5′-guanylimidodiphosphate (Gpp(NH)p) on the binding of the selective, high affinity μ-opiate receptor agonist, [3H]DAGO ([3H]Tyr-D-Ala-Gly-Mephe-Gly-ol), to rat brain membranes were studied in a low ionic strength 5 mM Tris–HCl buffer. Na+ and Li+ (50 mM) maximally increased [3H]DAGO binding (EC50 values for Na+,2.9 mM and Li, 6.2 mM) by revealing a population of low affinity binding sites. The density of high affinity [3H]DAGO binding sites was unaffected by Na+ and Li+, but was maximally increased by 50 mM K+ and Rb+ (EC50 values for K+, 8.5 mM and Rb+, 12.9 mM). Divalent cations (Ca2+, Mg2+; 50 mM) inhibited [3H]DAGO binding. Gpp(NH)p decreased the affinity of [3H]DAGO binding, an effect that was enhanced by Na+ but not by K+. The binding of the μ-agonist [3H]dihydromorphine was unaffected by 50 mM Na+ in 5 mM Tris–HCl. In 50 mM Tris–HCl, Na+ (50 mM) inhibited [3H]DAGO binding by decreasing the density of high affinity binding sites and promoting low affinity binding. The effects of Na+ in 5 mM and 50 mM Tris–HCl were also investigated on the binding of other opiate receptor agonists and antagonists. [3H]D-Ala-D-Leu-enkephalin binding was increased and inhibited, [3H]etorphine binding increased and was unchanged, and both [3H]bremazocine and [3H]naloxone binding increased by 50 mM Na+ in 5 mM and 50 mM Tris–HCl, respectively. These findings indicate that the in vitro effects of Na+ at μ- and possibly other opiate receptors in rat brain are dependent on the concentration of Tris–HCl used in the assay buffer, lower concentrations of Tris-HCl revealing novel regulatory effects for Na+ at μ-opiate receptors.
Effect of parathyroid hormone and antagonist on aortic cAMP levels
Authors: Bergmann C. , Schoefer P. , Stoclet J. C. , Gairard A.
Published: April 2011

Experiments were designed to further investigate the vasoactive mechanisms of parathyroid hormone (PTH) on vascular smooth muscle cells. Time courses of the cAMP responses to the fragment (1–34) of bovine PTH (bPTH (1–34)) on cAMP levels have been studied in rat isolated aorta and in aortic myocytes in primary culture. In both aorta and myocytes bPTH (1–34) induced an increase in cAMP levels that was maximal and reached, respectively, 1.6- and 1.9-fold the basal level after 2 min of contact with bPTH (1–34). The effect of bPTH (1–34) on aortic cAMP content was concentration dependent in the range of 30–300 nM. (Nle8,18, Tyr34)-bPTH (3–34)amide, an antagonist of bPTH (1–34) with a stimulant effect on renal and vascular adenylate cyclase activity, inhibited the cAMP-increasing effect of bPTH (1–34). These results are in favour of a role for cAMP in the vasodilating effect of PTH.
Ethanol-induced cardiac hypertrophy: effects of peripheral sympathectomy
Authors: Hirst M. , Adams M. A.
Published: April 2011

The development of cardiac hypertrophy was examined in rats that had undergone sympathectomy with 6-hydroxydopamine. After 4 days, the rats were given severely intoxicating doses of ethanol or isocalorically paired quantities of maltose–dextrin by intubation at 8-h intervals up to 48 h. The ethanol and sugar intubations were applied in a nutritionally adequate, liquid diet mix. The extent of the peripheral sympathectomy was evident from the absence of detectable quantities of noradrenaline in hearts of animals injected with the neurotoxin and in the reduced levels of excreted noradrenaline. The adrenal medullary catecholamine contents of sympathectomized rats were unchanged in the absence of ethanol; there were reduced quantities of adrenaline in the medullae of rats given ethanol. The adrenal glands of rats given ethanol were larger than those from control animals. Urine samples from sympathectomized and control rats, given ethanol, displayed equivalent increases in excreted adrenaline and noradrenaline. Increases in relative cardiac weight were evident in hearts from sympathectomized animals after 4 days of sympathectomy, and this change reached significance in the hearts from 6-hydroxydopamine-treated rats after a further 2 days on the control diet. Hearts from animals exposed to ethanol showed a marked, rapid development of cardiomegaly; after 24 h there was an increased mass of some 17%, which was sustained over the remaining 24-h period. The proportion of cardiac protein did not differ in the large hearts from ethanol-treated animals and those from their controls, hence myocardial oedema could not account for the increase in weight. The results of the study indicate that ethanol-induced cardiomegaly can occur in the absence of an intact cardiac sympathetic nerve supply.
Isolation of nonciliated bronchiolar epithelial (Clara) cells and alveolar type II cells from mouse lungs
Authors: Massey Thomas E. , Geddes Barbara A. , Forkert Poh-Gek
Published: April 2011

A method is described for the isolation of alveolar type II cells and nonciliated bronchiolar epithelial (Clara) cells from mouse lungs. Following digestion of lung tissue with Sigma type I protease, viable cells were isolated to 65% purity for type II cells (6.4 ± 1.5 × 105 cells/mouse) and 55–60% purity for Clara cells (2.6 ± 0.9 × 105 cells/mouse). Viability, as assessed by trypan blue exclusion, was routinely greater than 90% in all enriched cell fractions. Although minor mitochondrial changes occurred during isolation, the morphology of the cells showed good preservation, as revealed by electron microscopy. The isolated cells were found to be metabolically active, as indicated by the presence of 7-ethoxycoumarin deethylase (a cytochrome p-450-mediated activity). The highest activity of this enzyme (278 ± 116 pmol∙min−1∙mg protein−1) was found in the fraction enriched in Clara cells. The results indicate that this method produces viable cell populations that can be of value in investigations of the cellular distribution of lung metabolism activities.
Catecholamine and blood pressure regulation by gonadotropin-releasing hormone analogs in amphibians
Authors: Wilson John X. , Saleh Khaled J. , Armogan E. Davindra , Jaworska Ewa J.
Published: April 2011

Analogs of gonadotropin-releasing hormone (GnRH) occur in the brain, plasma, and sympathoadrenal system of anuran amphibians. The present experiments studied the effects of GnRH and [Trp7, Leu8]-GnRH on plasma catecholamines and cardiovascular function in conscious adult bullfrogs (Rana catesbeiana) and cane toads (Bufo marinus). Both GnRH analogs elicited dose-dependent (0.1–1 nmol∙kg−1) increases in arterial norepinephrine, epinephrine, and blood pressure levels when injected intravenously into toads. In bullfrogs, [Trp7, Leu8]-GnRH (1 nmol∙kg−1) increased arterial norepinephrine concentration approximately 10-fold without affecting the concentrations of norepinephrine sulfate, norepinephrine glucuronide, epinephrine, epinephrine sulfate, or epinephrine glucuronide. The noradrenergic response of bullfrogs to [Trp7, Leu8]-GnRH was specific to the neurohormone because it could be inhibited by [D-pGlu1, D-Phe2, D-Trp3,6]-GnRH. The sympathomimetic activities of the GnRH analogs did not depend on changes in temperature, which occur seasonally in natural habitats, because similar noradrenergic responses were observed at 4 and 22 °C. GnRH and [Trp7, Leu8]-GnRH (0.01–10 nmol∙kg−1) did not raise arterial blood pressure in bullfrogs despite their pressor actions in toads. This interspecific difference was remarkable because cardiovascular responses to norepinephrine, angiotensin II, and vasotocin in bullfrogs were similar to those in toads. The parallels between catecholamine and blood pressure responses suggest that epinephrine is the principal mediator of the blood pressure response to native GnRH analogs in toads. In bullfrogs, [Trp7, Leu8]-GnRH mobilizes norepinephrine but not epinephrine, and the noradrenergic effect is insufficient to raise blood pressure. These observations are consistent with a physiological role for native GnRH analogs in the regulation of the sympathoadrenal system in anuran amphibians.
Apparent dissociation between sympathetic activity and brown adipose tissue thermogenesis during pregnancy and lactation in golden hamsters
Authors: Trayhurn P. , Wusteman M. C.
Published: April 2011

Sympathetic activity has been assessed by measurements of noradrenaline turnover in brown adipose tissue and in the heart of golden hamsters during pregnancy and lactation. Noradrenaline turnover was not significantly altered in either tissue in pregnant or lactating hamsters, despite the atrophy of brown adipose tissue that occurs during reproduction. This suggests that sympathetic activity and brown adipose tissue thermogenesis are dissociated during pregnancy and lactation in golden hamsters. The results also indicate that the large increase in food intake during lactation does not lead to a diet-induced stimulation of the sympathetic nervous system.
Effect of a Prudhoe Bay crude oil on hepatic and placental drug metabolism in rats
Authors: Khan Sumsullah , Martin Marie , Rahimtula Anver D. , Payne Jeremiah F.
Published: April 2011

Administration of a Prudhoe Bay crude oil (PBCO) to pregnant rats resulted in induction of hepatic microsomal P-450 levels and various monooxygenases in a dose-dependent manner. The activities of aniline hydroxylase, benzo[a]pyrene hydroxylase, aminopyrine-N-demethylase, ethoxyresorufin-O-deethylase, and pentoxyresorufin-O-depentylase were increased 2–3-fold, 12–15-fold, 1.4–1.8-fold, 20–24-fold, and 6–8-fold, respectively, on gestation day 18, when a single dose of PBCO (5–10 mL/kg body weight, p.o.) had been administered 24 h earlier. Glutathione-S-transferase, UDPG transferase, and DT-diaphorase activities were also increased; however, maximum induction was noticed when crude oil was given 72 h earlier. Repeated exposure (day 6 – day 17, daily) of crude oil at lower levels was able to produce similar induction patterns in enzyme systems at day 18 of gestation. The xenobiotic-metabolizing enzyme systems were also induced transplacentally: treatment of pregnant rats with PBCO induced both placental and fetal hepatic enzyme systems. Liver microsomal P-450 contents, benzo[a]pyrene hydroxylase, and ethoxyresorufin-O-deethylase activities were increased 2-fold, 2–3-fold, and 10–12-fold, respectively in 18-day-old fetuses. Similar trends were noticed in placenta. Activities of phase II enzymes such as glutathione-S-transferase, UDPG transferase, and DT-diaphorase were also significantly elevated. It is suggested that crude oil induces maternal hepatic drug metabolism and that some of its constituents (mainly aromatic hydrocarbons) and (or) their metabolites pass through the placenta and thus induce drug-metabolizing enzymes transplacentally. The practical importance of the results in relation to human and environmental health is also discussed.
Failure of renal denervation to attenuate hypertension in Dahl NaCl-sensitive rats
Authors: Wyss J. Michael , Sripairojthikoon Wanida , Oparil Suzanne
Published: April 2011

In previous experiments we have demonstrated that the renal nerves play a significant role in all genetic and (or) induced models of hypertension that we have studied. The current experiments extended this research by investigating the contribution of the renal nerves to hypertension in the Dahl NaCl-sensitive rat. This was investigated by assessing the effect of bilateral phenol renal denervation carried out prior to initiation of a high NaCl (8% NaCl) diet. In two separate studies, renal denervation did not affect systolic blood pressure in either Dahl NaCl-sensitive rats or their normotensive counterparts, Dahl NaCl-resistant rats. Further, denervation did not increase absolute urinary sodium excretion, percent urinary sodium excretion, urinary volume output, or food or water intake; nor did it differentially alter creatinine clearance or body weight. Denervation was verified at the termination of each study by a greater than 80% depletion of renal noradrenaline stores. These results indicate that the renal nerves do not provide a major contribution to hypertension in the Dahl NaCl-sensitive rat.
L-656,224 (7-chloro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-4-benzofuranol): a novel, selective, orally active 5-lipoxygenase inhibitor
Authors: Belanger P. , Maycock A. , Guindon Y. , Bach T. , Dollob A. L. , Dufresne C. , Ford-Hutchinson A. W. , Gale P. H. , Hopple S. , Lau C. K. , Letts L. G. , Luell S. , McFarlane C. S. , MacIntyre E. , Meurer R. , Miller D. K. , Piechuta H. , Riendeau D. , Rokach J. , Rouzer C. , Scheigetz J.
Published: April 2011

L-656,224 (7-chloro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-4-benzofuranol) was a potent inhibitor of leukotriene biosynthesis in intact rat and human leukocytes and CXBG mastocytoma cells (IC50 values, 18–240 nM) and of crude human leukocyte and highly purified porcine leukocyte 5-lipoxygenase (IC50 value, 4 × 10–7 M). The selectivity of L-656,224 for 5-lipoxygenase was shown through the relative lack of activity of the compound on 12-lipoxygenase, 15-lipoxygenase, cyclooxygenase, catalase, and myeloperoxidase. The compound showed (i) oral activity against hyperalgesia induced in the rat paw by injection of yeast or platelet-activating factor, (ii) dyspnea in sensitized inbred rats induced by an aerosol of antigen, and (iii) bronchoconstriction induced by an aerosol of Ascaris in squirrel monkeys, suggesting a role for 5-lipoxygenase inhibitors in the treatment of asthma and peripheral pain.
The effect of d-fenfluramine on anterior pituitary hormone release in the rat: in vivo and in vitro studies
Authors: Serri O. , Rasio E.
Published: April 2011

Administration of d-fenfluramine, a serotonin-releasing drug, to male rats induced a dose-dependent increase in both serum prolactin and corticosterone concentrations. Serum growth hormone levels increased, but not significantly, at a dose of 1.25 mg/kg i.p. and decreased significantly at higher doses. When rats were pretreated with the serotonin uptake inhibitor fluoxetine (10 mg/kg i.p.) 30 min prior to injection of d-fenfluramine (5 mg/kg i.p.), the serum prolactin response to d-fenfluramine was partially inhibited, whereas the growth hormone response was not significantly modified. Fluoxetine pretreatment increased the serum corticosterone to the same level as did d-fenfluramine. d-Fenfluramine's effect on prolactin and growth hormone release was further tested in a hypothalamic–pituitary in vitro system. The addition of d-fenfluramine (5–500 ng/mL) for 30 min to rat hypothalami resulted in an enhancement of prolactin and growth hormone-releasing activities. These were expressed as the ability of the media in which the hypothalami had been incubated to stimulate prolactin and growth hormone release by cultured pituitary cells. The data suggest that the effect of d-fenfluramine on prolactin secretion is exerted through the hypothalamus and is probably mediated, at least partially, by a serotoninergic mechanism. The mechanism of d-fenfluramine's effect on corticosterone and growth hormone release needs further evaluation.
Spectrum of effects of dietary long-chain fatty acids on rat intestinal glucose and lipid uptake
Authors: Thomson A. B. R. , Keelan M. , Garg M. , Clandinin M. T.
Published: April 2011

Isocaloric modification in the ratio of dietary polyunsaturated-to-saturated fatty acids influences intestinal uptake of actively and passively transported nutrients. This study was undertaken to determine which dietary fatty acid was responsible for these alterations in absorption. Adult female rats were fed isocaloric semisynthetic diets high in palmitic and stearic acids (SFA), oleic acid (OA), linoleic acid (LA), or linolenic acid (LNA). An in vitro technique was used to measure the uptake of varying concentrations of glucose as well as a series of fatty acids and cholesterol. Jejunal uptake of 40 mM glucose was highest in rats fed SFA and lowest in those fed LA; ileal glucose uptake was similar in OA, LA, and LNA, but was lowest in SFA. Jejunal uptake of medium-chain fatty acids (8:0–12:0) was higher in OA than in other diet groups; ileal uptake of medium-chain fatty acids was unaffected by diet. Jejunal and ileal uptake of 18:2 was higher in LNA than in SFA or OA; the uptake of the other long-chain saturated or unsaturated fatty acids was unchanged by diet. The ileal but not the jejunal uptake of cholesterol was increased in LA as compared with SFA or OA, and reduced in LNA as compared with LA. These transport changes were not explained by differences in the animals' food consumption, body weight gain, intestinal mass, or mucosal surface area. We postulate that these diet-induced transport alterations may be mediated via changes in brush border membrane phospholipid fatty acyl composition. Thus, intestinal transport of nutrients may be varied by isocaloric changes in the dietary content of individual fatty acids.
BAY-K-8644-stimulated amylase secretion from pancreatic acinar cells
Authors: Heisler Seymour , Desjardins Diane , Belles-Isles Marthe
Published: April 2011

Pancreatic acinar cells do not contain depolarization-sensitive calcium channels. Nonetheless, in the current study, the calcium channel activator, BAY-K-8644, was found to stimulate a time- and concentration-dependent increase in the spontaneous release of amylase. Secretion was dependent on the presence of extracellular calcium in the incubation medium. Racemic BAY-K-8644 and (or) its S(−)optical isomer did not enhance the secretory response to either carbachol or cholecystokinin octapeptide; however, when co-applied with either phorbol ester, vasoactive intestinal peptide, or forskolin, they potentiated amylase secretion. Nifedipine and the R(+)isomer of BAY-K-8644, which are both calcium channel antagonists, did not alter basal or forskolin-stimulated amylase secretion, and [3H]nitrendipine did not bind to acinar cell membranes. Neither atropine nor dibutyryl cGMP, inhibitors of cholinergic and cholecystokininergic receptors, respectively, affected BAY-K-8644-induced amylase secretion. While BAY-K-8644 stimulated concentration-dependent cGMP synthesis in acinar cells, it had no effect on basal or forskolin-stimulated cAMP formation. The data suggest that BAY-K-8644 may bind to acinar cell sites that are not functional calcium channel proteins but are coupled nevertheless to the secretory response, and that calcium channel antagonists do not bind to these sites. The mechanism of the secretagogue action of BAY-K-8644 remains to be elucidated.
Thermogenic effects of dihydrocodeine in the rat
Authors: Rothwell Nancy J. , Stock Michael J. , Tedstone Alison E.
Published: April 2011

The object of this study was to assess the effects of dihydrocodeine on thermogenesis and brown adipose tissue activity in the rat from measurements of oxygen consumption and blood flow. Acute injection of dihydrocodeine tartrate (s.c.) stimulated resting oxygen consumption [Formula: see text] in Sprague–Dawley rats in a dose-dependent manner (0.5–50 mg/kg), with a peak response (40–45% increase) occurring at 10–25 mg/kg. This effect was also observed in urethane-anaesthetized rats (although the effect was reduced) and in conscious animals following gastric intubation with the drug. Pretreatment of rats with either a β-adrenergic antagonist (propranolol, 20 mg/kg), ACTH (4 g/kg), or an opiate antagonist (WIN44441-1, 2 mg/kg) significantly reduced the response to dihydrocodeine, whereas corticosterone injection (5 mg/kg) enhanced the effect. Surgical adrenalectomy or hypophysectomy (HYPX) almost completely abolished the thermogenic effect of dihydrocodeine. Dihydrocodeine also stimulated [Formula: see text] in lean (58% increase) and genetically obese Zucker rats (69% increase), and in both Zucker genotypes these responses were only slightly affected by HYPX, but enhanced in HYPX rats treated daily with corticosterone (1 mg/kg). Tissue blood flow, assessed from the distribution of radiolabelled microspheres, was unaffected in white adipose tissue, skeletal muscle, testes, kidney, brain, and liver (arterial supply) after a single injection of dihydrocodeine (25 mg/kg), but flow to interscapular and perirenal brown adipose tissue was increased by 9- to 10-fold. Surgical sympathectomy of brown adipose tissue prevented the increase in blood flow. These potent thermogenic effects of dihydrocodeine in the rat appear to result from sympathetic activation of heat production in brown fat and to involve opiate receptors, but can also be modified by pituitary and (or) adrenal hormones.
Aspirin enhances evaporation in hydrated and dehydrated rats
Authors: Turlejska E. , Baker M. A.
Published: April 2011

The effect of acetysalicylic acid (aspirin) on thermoregulation in a warm environment was studied in hydrated and dehydrated adult rats to test the hypothesis that dehydration hyperthermia can be modified by an antipyretic drug. Metabolic rate (MR), evaporative water loss (EWL), and deep body temperature (Tb) were measured during 2 h of exposure to an ambient temperature of 36 °C after the rats had received an oral pellet of aspirin (100 mg∙kg−1) or placebo. The dehydrated placebo group had a higher Tb and lower EWL than the hydrated placebo group. Aspirin increased MR and EWL in both hydrated and dehydrated animals. Aspirin did not affect Tb in hydrated rats, but reduced Tb by 0.2 °C in dehydrated rats during the heat exposure. The elevation in EWL appears to be a thermoregulatory response to increased heat production in both hydrated and dehydrated animals after aspirin treatment. The possibility that aspirin may act in dehydrated animals to restore central thermosensitivity toward hydrated levels needs to be tested further.
The ex-vivo effects of thyroid status and extracellular calcium concentration on rat atrial and ventricular electrophysiology
Authors: Gristwood R. W. , Rothaul A. L.
Published: April 2011

The purpose of this study was to explore the relationship between the thyroid status and both ventricular and atrial electrophysiology in the rat. The study was extended to consider the effects of altering the extracellular calcium concentration. The work was performed in two sections. First, hypothyroid animals were compared with euthyroid (untreated animals); second, hypothyroid animals were compared with hyperthyroid animals. Rats were rendered hypothyroid by pretreatment with the goitrogen methimazole and hyperthyroid by additional treatment with triiodothyronine. Action potential recordings were obtained using standard microelectrode techniques. Action potential measurements were made initially in a Krebs solution to which had been added 2.55 mM calcium (higher Ca Krebs solution) and at the end of each experiment after stabilization with Krebs solution to which had been added 1.28 mM calcium (lower Ca Krebs solution). Assessment of the change in action potential duration on transition from higher to lower Ca Krebs solution revealed that the euthyroid preparations demonstrated less prolongation of action potential duration than the hypothyroid group, and the hyperthyroid group showed hardly any response to reduction in calcium concentration.
Central interaction of the brain atrial natriuretic polypeptide (ANP) system and the brain rennin–angiotensin system in ANP secretion from heart—evidence for possible brain–heart axis
Authors: Itoh Hiroshi , Nakao Kazuwa , Yamada Takayuki , Morii Narito , Shiono Shozo , Sugawara Akira , Saito Yoshihiko , Mukoyama Masashi , Arai Hiroshi , Imura Hiroo
Published: April 2011

To elucidate the involvement of the brain renin–angiotensin system and the brain atrial natriuretic polypeptide (ANP) system in the regulation of ANP secretion from the heart, the effects of intracerebroventricular administration of angiotensin II and ANP on the plasma ANP level were examined in conscious unrestrained rats. The intracerebroventricular administration of angiotensin II at doses of 100 ng and 1 μg significantly enhanced ANP secretion induced by volume-loading with 3-mL saline infusion (peak values of the plasma ANP level: control, 220 ± 57 pg/mL; 100 ng angiotensin II, 1110 ± 320 pg/mL, p < 0.01; 1 μg angiotensin II, 1055 ± 60 pg/mL, p < 0.01). The intracerebroventricular injection of angiotensin II at the same doses alone had no significant effect on the basal plasma ANP level. The enhancing effect of central angiotensin II on ANP secretion induced by volume-loading was significantly attenuated by pretreatment with the intravenous administration of the V1-receptor antagonist of vasopressin or with the intracerebroventricular administration of phentolamine. The intracerebroventricular administration of α-rANP(4–28) (5 μg) had no significant influence on the basal plasma ANP level; however, it significantly attenuated central angiotensin II potentiating effect of volume-loading induced ANP secretion. These results indicate that the brain rennin–angiotensin system regulates ANP secretion via the stimulation of vasopressin secretion and (or) via the activation of the central α-adrenergic neural pathway, and that the brain ANP system interacts with the brain renin–angiotensin system in the central modulation of ANP secretion from the heart. The result further supports the proposed antagonistic relationship between the brain ANP system and the brain renin–angiotensin system in body fluid and blood pressure homeostasis.
Alterations in atrial natriuretic peptide receptors in rat brain nuclei during hypertension and dehydration
Authors: Saavedra Juan M.
Published: April 2011

We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (99–126) in the rat brain. Atrial natriuretic peptide receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood pressure control. Spontaneously (genetic) hypertensive rats showed much lower numbers of atrial natriuretic peptide receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and in the choroid plexus. These changes are in contrast with those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of the atrial natriuretic peptide. In acute dehydration after water deprivation, as well as in chronic dehydration such as that present in homozygous Brattleboro rats, there was an up-regulation of atrial natriuretic peptide receptors in the subfornical organ. Thus, circumventricular organs contain atrial natriuretic peptide receptors that could respond to variations in the concentration of circulating peptide. The localization of atrial natriuretic peptide receptors and the alterations in their regulation present in hypertensive and dehydrated rats indicate that these brain receptors are related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function. Atrial natriuretic peptide receptors in the choroid plexus may be related to the formation of cerebrospinal fluid.
Neuropeptide Y does not inhibit the release of α-MSH from the pars intermedia of the rat adenohypophysis
Authors: Kraicer J. , Lussier B. , Kotanen S. , Moor B. C.
Published: April 2011

Neuropeptide Y in concentrations from 10−8 to 10−6 M inhibits the release of α-MSH from the frog (Rana pipiens) pituitary in a reversible, sustained, and concentration-related manner. However, it does not inhibit the release of α-MSH from the rat pars intermedia. Thus, while neuropeptide Y may play a role in the control of α-MSH release in amphibia, it appears not to be a regulatory peptide for the mammalian pars intermedia.
A voltage clamp study of the glutamate responsive neuromuscular junction in Drosophila melanogaster
Authors: McLarnon James G. , Quastel David M. J.
Published: April 2011

The point and single electrode voltage clamp methods have been used to study the characteristics of junctional currents in Drosophila melanogaster larvae muscle fibers and the modulation of these currents by excitatory amino acids, short and long chain n-alkanols, and pentobarbital. The decay phase of junctional currents in Drosophila was found to be dominated by cooperativity in transmitter binding associated with reverberation, that is, repeated binding of transmitter with receptors as the transmitter molecules diffuse away from the active region. The current decay does not directly reflect the closure of ion channels and is qualitatively similar to the decay of miniature end-plate currents at the mouse neuromuscular junction after poisoning of acetylcholinesterase by paraoxon. In Drosophila an increase in membrane hyperpolarization both slows the time course of current decay and increases the degree of reverberation. The application of excitatory amino acids including glutamate, N-methyl-D-aspartate, quisqualate, and kainate causes a significant decrease in the amplitude of the junctional currents, a prolongation of the decay time course, and a reduction in reverberation of transmitter. The height of junctional currents is also diminished by the n-alkanols ethanol, pentanol, and octanol and by the barbiturate pentobarbital; ethanol also hastened the time course of decay of the currents.
In vivo modulation by α2-adrenoceptors of adrenal catecholamine release in the anaesthetized dog
Authors: Foucart Sylvain , Champlain Jacques de , Nadeau Reginald
Published: April 2011

In this study, the reversal of the potentiating effect of idazoxan, a selective α2-antagonist, on adrenal catecholamine release elicited by splanchnic nerve stimulation in anaesthetized and vagotomized dogs, was investigated with the use of oxymetazoline, a selective α2-agonist. Stimulation of the left splanchnic nerve (5.0-V pulses of 2 ms duration for 3 min at a frequency of 2 Hz) was applied before and 20 min after the i. v. injection of each drug. Blood samples were collected in the adrenal vein before and at the end of each stimulation. The results show that the release of catecholamines induced by electrical stimulation was potentiated by 50% after idazoxan injection (0.1 mg/kg). This enhanced response was significantly antagonized by the subsequent injection of oxymetazoline (2 μg/kg). The α2-modulating effect appears to be related to the amount of catecholamines released during the stimulation, since by subgrouping of the data on the basis of the degree of potentiation by idazoxan, it was observed that this drug was more efficient when catecholamine release was higher during control stimulation. In contrast, the reversing effect of oxymetazoline was found to be more pronounced when catecholamine release was lower. These results thus suggest that the sensitivity of the α2-adrenoceptor mechanism may depend upon the in situ concentration of adrenal catecholamine release during electrical stimulation and that the potentiating effect of α2-blockade can be reversed by activation of those receptors by a selective α2-agonist.