bluuebunny/crossref_metadata_2025 huggingface dataset:
Bidirectional communication between the pineal gland and the immune system
Authors: Skwarlo-Sonta Krystyna , Majewski Pawel , Markowska Magdalena , Oblap Ruslan , Olszanska Bozenna
Published: June 2003

The pineal gland is a vertebrate neuroendocrine organ converting environmental photoperiodic information into a biochemical message (melatonin) that subsequently regulates the activity of numerous target tissues after its release into the bloodstream. A phylogenetically conserved feature is increased melatonin synthesis during darkness, even though there are differences between mammals and birds in the regulation of rhythmic pinealocyte function. Membrane-bound melatonin receptors are found in many peripheral organs, including lymphoid glands and immune cells, from which melatonin receptor genes have been characterized and cloned. The expression of melatonin receptor genes within the immune system shows species and organ specificity. The pineal gland, via the rhythmical synthesis and release of melatonin, influences the development and function of the immune system, although the postreceptor signal transduction system is poorly understood. Circulating messages produced by activated immune cells are recipro cally perceived by the pineal gland and provide feedback for the regulation of pineal function. The pineal gland and the immune system are, therefore, reciprocally linked by bidirectional communication.Key words: pineal gland, melatonin, immunity, melatonin receptors, melatonin receptor transcripts.
Development of the brain: a vital role for cerebrospinal fluid
Authors: Miyan Jaleel A , Nabiyouni Mohammad , Zendah Mahjuib
Published: June 2003

There has been considerable recent progress in understanding the processes involved in brain development. An analysis of a number of neurological conditions, together with our studies of the hydrocephalic Texas (H-Tx) rat, presents an important role for cerebrospinal fluid (CSF) in the developmental process. The fluid flow is essentially one-way and the location of the choroid plexuses in the lateral, third, and fourth ventricles allows for the possibility of new components being added to the fluid at these points. The role of the fourth ventricular CSF is particularly interesting since this is added to the fluid downstream of the cerebral hemisphere germinal epithelium (the main site of cortical cell proliferation and differentiation) and is destined for the basal cisterns and subarachnoid space suggesting different target cells to those within the ventricular system. Moreover, other sources of additions to the CSF exist, notably the subcommissural organ, which sits at the opening of the third ventricle into the cerebral aqueduct and is the source of Reisner's fibre, glycoproteins, and unknown soluble proteins. In this paper a model for the role of CSF is developed from studies of the development of the cortex of the H-Tx rat. We propose that CSF is vital in controlling development of the nervous system along the whole length of the neural tube and that the externalisation of CSF during development is essential for the formation of the layers of neurones in the cerebral cortex.Key words: cerebrospinal fluid, cerebral cortex, development, rat, hydrocephalus.
In vivo gene transfer to dissect neuronal mechanisms regulating cardiorespiratory function
Authors: Paton Julian F.R , Waki Hidefumi , Kasparov Sergey
Published: June 2003

This lecture reviews recent information from our laboratory regarding brainstem mechanisms regulating the arterial baroreceptor reflex. Our long-term goal is to understand some of the mechanisms involved in the etiology of essential hypertension. Our hypothesis is that this problem may arise, in part, because of changes within brainstem circuits controlling arterial pressure, and in particular to occlusion of baroreceptive information at the level of the primary afferent relay within the brainstem. Although it is established that baroreceptors provide a mechanism for short-term regulation of arterial pressure, there is convincing evidence that they also play a role in its long-term control (see Thrasher 2002, for an example). It follows that dysfunction of this reflex circuit could contribute to high blood pressure levels. Here, we discuss the central actions of angiotensin II on the baroreceptor reflex circuitry within the nucleus of the solitary tract (NTS) for arterial pressure control. Our findings have led us to hypothesize a novel form of intercellular communication within the NTS, one of vascular-neuronal signaling.Key words: baroreceptor reflex, nitric oxide, eNOS, nucleus tractus solitarii, adenovirus, somatic gene transfer.
Phosphate absorption inAplysiacalifornicagut: glucocorticoid inhibition
Authors: Gerencser George A , Loo Stanley Y , Robbins Frank W , Zhang Jianliang
Published: June 2003

Apical membranes of Aplysia californica foregut epithelia contain a sodiumphosphate symporter. Dexamethasone inhibited the absorptive activity of the sodiumphosphate symporter, whereas amiloride had no effect on the sodiumphosphate symporter. It appears that glucocorticoids or their molluscan equivalent play a role in the overall regulation of phosphate homeostasis by the Aplysia californica gut.Key words: phosphate absorption, sodiumphosphate symporter, glucocorticoid inhibition.
Synthesis and degradation of endothelin-1
Authors: D'Orléans-Juste P , Plante M , Honoré J C , Carrier E , Labonté J
Published: June 2003

The endothelin-converting enzyme (ECE) is the main enzyme responsible for the genesis of the potent pressor peptide endothelin-1 (ET-1). It is suggested that the ECE is pivotal in the genesis of ET-1, considering that the knockout of both genes generates the same lethal developments during the embryonic stage. Several isoforms of the ECE have been disclosed, namely ECE-1, ECE-2, and ECE-3. Within each of the first two groups, several sub-isoforms derived through splicing of single genes have also been identified. In this review, the characteristics of each sub-isoform for ECE-1 and 2 will be discussed. It is important to mention that the ECE is, however, not the sole enzyme involved in the genesis of endothelins. Indeed, other moieties, such as chymase and matrix metalloproteinase II, have been suggested to be involved in the production of ET intermediates, such as ET-1 (131) and ET-1 (132), respectively. Other enzymes, such as the neutral endopeptidase 2411, is curiously not only involved in the degradation and inactivation of ET-1, but is also responsible for the final production of the peptide via the hydrolysis of ET-1 (131). In this review, we will attempt to summarize, through the above-mentioned characteristics, the current wisdom on the role of these different enzymes in the genesis and termination of effect of the most potent pressor peptide reported to date.Key words: endothelin converting enzyme, endothelin-1, isoforms, human, inhibitors, chymase, ET-1 (131).
Evaluation of the antiulcerogenic activity of violacein and its modulation by the inclusion complexation with β-cyclodextrin
Authors: Durán Nelson , Justo Giselle Z , Melo Patrícia S , De Azevedo Mariângela B.M , Souza Brito Alba R.M , Almeida Ana B.A , Haun Marcela
Published: June 2003

The effects of β-cyclodextrin (βCD) inclusion complexation on the ability of violacein to prevent gastric ulceration in mice were studied. ViolaceinβCD inclusion complexes were prepared in 1:1 and 1:2 molar ratios and analysed by differential scanning calorimetry and powder X-ray diffractometry. Violacein previously administered orally at 10 mg/kg significantly reduced indomethacin-induced gastric lesions, as well as 100 mg/kg of cimetidine (positive control). However, βCD complexation in both molar ratios significantly potentiated the protective action of violacein. In the HClethanol-induced gastric ulcer model, violacein and the 1:2 inclusion complex (10 mg/kg, p.o.) inhibited gastric damage by almost 85%, whereas a 63% reduction was observed for the positive control, lansoprazole, at 30 mg/kg. In contrast, treatment with the 1:1 inclusion complex resulted in almost total disappearance of the antiulcer activity in this model. No significant changes in stress-induced gastric injury were found. In addition, the 1:2 inclusion complex improved the antilipoperoxidant activity of violacein in rat liver cells exposed to t-butyl hydroperoxide, whereas the 1:1 complex was less active than violacein. In summary, the 1:2 βCD inclusion complex has gastroprotective properties similar to or higher than that of violacein. An increase in mucosal defensive mechanisms and protection against peroxidative damage might be involved.Key words: violacein, β-cyclodextrin, gastric ulcer, lipid peroxidation, hepatocyte.
Growth hormone in the nervous system: autocrine or paracrine roles in retinal function?
Authors: Harvey S , Kakebeeke M , Murphy A E , Sanders E J
Published: June 2003

Growth hormone (GH) is primarily produced in the pituitary gland, although GH gene expression also occurs in the central and autonomic nervous systems. GH-immunoreactive proteins are abundant in the brain, spinal cord, and peripheral nerves. The appearance of GH in these tissues occurs prior to the ontogenic differentiation of the pituitary gland and prior to the presence of GH in systemic circulation. Neural GH is also present in neonates, juveniles, and adults and is independent of changes in pituitary GH secretion. Neural GH is therefore likely to have local roles in neural development or neural function, especially as GH receptors (GHRs) are widespread in the nervous system. In recent studies, GH mRNA and GH immunoreactive proteins have been identified in the neural retina of embryonic chicks. GH immunoreactivity is present in the optic cup of chick embryos at embryonic day (ED) 3 of the 21-d incubation period. It is widespread in the neural retina by ED 7 but also present in the nonpigmented retina, choroid, sclera, and cornea. This immunoreactivity is associated with proteins in the neural retina comparable in size with those in the adult pituitary gland, although it is primarily associated with 1516 kDa moieties rather than with the full-length molecule of approximately 22 kDa. These small GH moieties may reflect proteolytic fragments of "monomer" GH and (or) the presence of different GH gene transcripts, since full-length and truncated GH cDNAs are present in retinal tissue extracts. The GH immunoreactivity in the retina persists throughout embryonic development but is not present in juvenile birds (after 6 weeks of age). This immunoreactivity is also associated with the presence of GH receptor (GHR) immunoreactivity and GHR mRNA in ocular tissues of chick embryos. The retina is thus an extrapituitary site of GH gene expression during early development and is probably an autocrine or paracrine site of GH action. The marked ontogenic pattern of GH immunoreactivity in the retina suggests hitherto unsuspected roles for GH in neurogenesis or ocular development.Key words: growth hormone, growth hormone receptor, nervous system, retina, autocrine, paracrine.
RyR1/SERCA1 cross-talk regulation of calcium transport in heavy sarcoplasmic reticulum vesicles
Authors: Gilchrist James S.C , Palahniuk Chris , Abrenica Bernard , Rampersad Penelope , Mutawe Mark , Cook Tom
Published: June 2003

We investigated the functional interdependence of sarco-endoplasmic reticulum Ca2+ATPase isoform 1 and ryanodine receptor isoform 1 in heavy sarcoplasmic reticulum membranes by synchronous fluorescence determination of extravesicular Ca2+transients and catalytic activity. Under conditions of dynamic Ca2+exchange ATPase catalytic activity was well coordinated to ryanodine receptor activation/inactivation states. Ryanodine-induced activation of Ca2+release channel leaks also produced marked ATPase activation in the absence of measurable increases in bulk free extra vesicular Ca2+. This suggested that Ca2+pumps are highly sensitive to Ca2+release channel leak status and potently buffer Ca2+ions exiting cytoplasmic openings of ryanodine receptors. Conversely, ryanodine receptor activation was dependent on Ca2+-ATPase pump activity. Ryanodine receptor activation by cytosolic Ca2+was (i) inversely proportional to luminal Ca2+load and (ii) dependent upon the rate of presentation of cytosolic Ca2+. Progressive Ca2+filling coincided with progressive loss of Ca2+sequestration rates and at a threshold loading, ryanodine-induced Ca2+release produced small transient reversals of catalytic activity. These data indicate that attainment of threshold luminal Ca2+loads coordinates sensitization of Ca2+release channels with autogenic inhibition of Ca2+pumping. This suggests that Ca2+-dependent control of Ca2+release in intact heavy sarcoplasmic reticulum membranes involves a Ca2+- mediated "cross-talk" between sarco-endoplasmic reticulum Ca2+ATPase isoform1 and ryanodine receptor isoform 1.Key words: Ca2+, sarcoplasmic reticulum, RyR, SERCA, calsequestrin, ryanodine.
Sex steroid communication in the ring dove brain during courtship
Authors: Belle Mino David Charles , Tsutsui Kazuyoshi , Lea Robert William
Published: June 2003

This review examines possible role of progesterone receptor (PR) and androgen receptor (AR) "cross-talk" in the expression of courtship behaviour in the ring dove (Streptopelia risoria). In doves, although androgen has been mostly associated with aggressive courtship behaviour and progesterone with the initiation of incubation, progesterone administration to courting birds terminates the aggressive component of courtship whilst having no effect on nesting behaviour. Recent results in doves have identified a high density of androgen receptor and progesterone receptor immu no reactivity (AR-ir and PR-ir) in the hypothalamus of both sexes in regions known to be directly involved in courtship and incubation behaviour. Nuclear AR-ir in courting birds is widespread throughout the brain. Nuclear PR-ir is only localized in discrete regions of the preoptic hypothalamus of both sexes. In the anterior and posterior hypothalamus of courting birds an increase number of AR-ir and PR-ir neurons colocalizes (7090%) in the nucleus preopticus anterior (POA), nucleus preopticus medialis (POM), nucleus preopticus paraventricularis magnocellularis (PPM), nucleus hypothalami lateralis posterioris (PLH), and tuberal hypothalamus (Tu). A lower percentage of colocalization is seen in birds at other stages of the breeding cycle. The high percentage of AR-ir and PR-ir colocalization in the preoptic hypothalamus of courting doves supports previous reports involving progesterone acting in these brain regions to terminate the androgen-dependent aggressive courtship behaviour in male doves. The increase in PR-ir staining intensity in AR-ir neurons in courting birds suggests that this progesterone-dependent termination of aggressive courtship display in males occurs at the receptor level and may be orchestrated by central oestrogen.Key words: androgen receptor, progesterone receptor, cross-talk, colocalization, ring dove.
Effects of contrast media on erythrocyte aggregation during sedimentation
Authors: Huang Xuequn , Yoshikoshi Akio , Hirano Kunihiro , Sakanishi Akio
Published: June 2003

To evaluate the effects of contrast media (CMs) on erythrocyte aggregation, we measured the erythrocyte sedimentation with Westergren method at 25°C. CMs were diatrizoate (Urografin® 76%) for ionic CM and iopamidol (Iopamiron® 370) for nonionic CM. Swine red blood cells (RBCs) were suspended in autologous plasma containing diatrizoate (URO), iopamidol (IOP), and saline (SAL) at 6.7% w/w, as well as in plasma alone (PLA), at 40% of the hematocrit. Sigmoid sedimentation curves were fitted to the Puccini et al. (1977) equation, and the average number of RBCs per aggregate m was calculated by Stokes' law against the time t. According to the MurataSecomb (1988) theory we estimated the collision rate K between two aggregates from dm/dt in the stationary phase during sedimentation. Corresponding to the maximal ESR, the dm/dt (in cells/s) was 0.52 in PLA, 0.09 in SAL, 0.06 in URO and 0.03 in IOP, so that K also decreased in proportion to dm/dt from 145 fL/s in PLA to 8 fL/s in IOP. Both the ionic and nonionic CMs tend to inhibit the RBC aggregation more than that in SAL; the latter iopamidol appears to be inhibitory more than the former diatrizoate in autologous plasma.Key words: erythrocyte sedimentation, RBC aggregation, contrast media, diatrizoate, iopamidol.
Bioavailability of anthocyanidin-3-glucosides following consumption of red wine and red grape juice
Authors: Frank Thomas , Netzel Michael , Strass Gabriele , Bitsch Roland , Bitsch Irmgard
Published: June 2003

Pharmacokinetic parameters and the bioavailability of several dietary anthocyanins following consumption of red wine and red grape juice were compared in nine healthy volunteers. They were given a single oral dose of either 400 mL of red wine (279.6 mg total anthocyanins) or 400 mL of red grape juice (283.5 mg total anthocyanins). Within 7 h, the urinary excretion of total anthocyanins was 0.23 and 0.18% of the administered dose following red grape juice and red wine ingestion, respectively. Pharmacokinetic parameters derived from plasma and urine concentrations exhibited higher variability after ingestion of red grape juice. Compared to red grape juice anthocyanins, the relative bioavailability of red wine anthocyanins was calculated to be 65.7, 61.3, 61.9, 291.5, 57.1, and 76.3% for the glucosides of cyanidin, delphinidin, malvidin, peonidin, petunidin, and its sum (referred to as total anthocyanins), respectively. Bioequivalence was established for none of the anthocyanins. On a low level, urinary excretion of anthocyanins was fast, and the excretion rates seem to exhibit monoexponential characteristics over time after ingestion of both red grape juice and red wine. Due to low bioavailability, any significant contribution of anthocyanins to health protecting properties of red wine or red grape juice seems questionable, but the clinical relevance of these findings awaits further investigation.Key words: pharmacokinetics, anthocyanins, glycosides, bioavailability, humans.
Thyroid hormone-induced sulfate absorption in Aplysia californica gut is mediated by protein synthesis
Authors: Gerencser George A , Loo Stanley Y , Zhang Jianliang
Published: June 2003

Mucosal membranes of foregut epithelia of Aplysia californica contain a sodiumsulfate symporter that is stimulated by triiodothyronine. Actinomycin D, puromycin, or cycloheximide inhibited the triiodothyronine-stimulated sulfate absorption. It appears that thyroid hormone manifests its effects on sulfate absorption in the A. californica gut through protein synthesis.Key words: sulfate absorption, sodiumsulfate symporter, thyroid hormone, protein synthesis.
Spatiotemporal dynamics of reentrant ventricular tachycardias in canine myocardial infarction: pharmacological modulation
Authors: Hélie François , Vinet Alain , Cardinal René
Published: June 2003

During the transition from a slow to rapid depolarization rhythm, rate-dependent sodium channel blockade develops progressively and increases from beat to beat under procainamide but more abruptly under lidocaine. We investigated the consequences of such differences on the dynamic course and stability of reentrant tachycardias at their onset. Procainamide and lidocaine were infused to equipotent plasma concentrations in canines with three-day-old myocardial infarction. We measured the activation times (ms) and maximum slopes of negative deflections in activation complexes (absolute value: |dV/dtmax| in mV/ms) in 191 unipolar electrograms recorded from ischemically damaged subepicardial muscle during programmed stimulation inducing reentrant tachycardias. Procainamide caused a greater reduction in |dV/dtmax| than did lidocaine in the responses to basic stimulation, and it favored the occurrence of cycle length prolongation at tachycardia onset as the |dV/dtmax| decreased progressively in successive beats. This resulted in conduction block and tachycardia termination in three of eight preparations. In contrast, lidocaine caused a greater depression in |dV/dtmax| in response to closely coupled extrastimuli, but |dV/dtmax| remained constant or even improved thereafter, and none of the tachycardias terminated spontaneously under lidocaine (n = 9). However, the reentrant circuits remained spatially unstable, and lidocaine favored the occurrence of cycle length dynamics displaying constant or decreasing trends. This study supports the notion that cycle length dynamics at tachycardia onset are determined by the properties of the reentrant substrate and their pharmacological modulation. Key words: lidocaine, procainamide, reentry, ventricular tachycardia, cycle length dynamics.
Working heart function in diabetes is not improved by spironolactone treatment
Authors: Verma Subodh , Yuen Violet G , Badiwala Mitesh , Anderson Todd J , McNeill John H
Published: June 2003

Aldosterone antagonism has emerged as an important strategy for end-stage congestive heart failure. To evaluate the potential contribution of aldosterone towards the cardiac complications of diabetes, this study examined the effects of chronic aldosterone receptor blockade (with spironolactone) on isolated working heart function in streptozotocin (STZ) - induced diabetic rats. Wistar rats were divided into four groups: control, control spironolactone-treated, diabetic, and diabetic spironolactone-treated. Following chronic spironolactone treatment (8 weeks), cardiac function was assessed in terms of the rate of contraction (+dP/dT), rate of relaxation (dP/dT), and left ventricular developed pressure (LVDP). Untreated diabetic rats exhibited marked cardiac dysfunction when compared with age matched controls (p < 0.001). Long-term spironolactone treatment did not improve these parameters. These data demonstrate the lack of beneficial effects of aldosterone receptor blockade on isolated working heart function in diabetes.Key words: aldosterone, streptozotocin-induced diabetes, aldosterone receptor blocker, spironolactone, cardiac function.
Effects of simvastatin and pravastatin on peroxidation of erythrocyte plasma membrane lipids in patients with type 2 hypercholesterolemia
Authors: Koter Maria , Franiak Ida , Broncel Marlena , Chojnowska-Jezierska Julita
Published: June 2003

Since hypercholesterolemia directly modifies the composition of erythrocytes plasma membrane, the influence of statins on erythrocytes has been researched. The beneficial effects of statins on clinical events may involve mechanisms that modify endothelial dysfunction, plaque stability, thrombus formation and inflammatory responses. The aim of the study was to evaluate the hypolipemic efficacy and effects of pravastatin and simvastatin on erythrocyte membrane fluidity and damage of erythrocytes in patients with type 2 hypercholesterolemia in comparison with a control group of healthy subjects. The study involved 53 patients affected by type 2 hypercholesterolemia (mean age, 53.3 ± 10.3) with initial total serum cholesterol (TC) levels > 250 mg/dL, LDL-cholesterol (LDL-C) levels > 170 mg/dL, and triglycerides (TG) levels < 400 mg/dL. The control group consisted of 30 healthy individuals (mean age 56.9 ± 6.3). Statins were given for 12 weeks. The dosages for oral administration of simvastatin and pravastatin were 20 mg/day. Laboratory tests were carried out before and after 4 and 12 weeks of the pharmacological treatment. The damage to plasma membrane of erythrocytes was measured on the basis of lipid peroxidation. The fluidity of plasma membrane of erythrocytes was determined by electron paramagnetic resonance (EPR) spectroscopy, using two spin labels: 5-DSA and 16-DSA. The cholesterol level in the membrane of red blood cells was estimated. Simvastatin and pravastatin reduced the total cholesterol concentration and LDL-cholesterol in plasma, as well as the cholesterol concentration in erythrocytes membranes. Hypercholesterolemia induced changes in the basic properties of human erythrocyte plasma membrane, including its fluidity and the intensity of lipid peroxidation. These results indicate that the simvastatin and pravastatin therapy reverses the alteration in the erythrocyte plasma membrane properties.Key words: hypercholesterolemia, cholesterol, erythrocyte, plasma membrane, peroxidation, spin labels, statins.
Characterization of the NTPDase activities in the mesentery pre- and post-capillary circuits of the guinea pig
Authors: Duval M , Beaudoin A R , Bkaily G , Gendron F P , D'Orléans-Juste P
Published: June 2003

NTPDase is one of the principal enzymes involved in the sequential hydrolysis of ATP. In the present study, the presence and functionality of NTPDase in the mesenteric vein and artery were examined. Adenosine triphosphate (ATP) (0.011000 pmol) induces a dose-dependent vasodilation in the isolated arterial and venous mesenteric vasculatures of the guinea pig. Adenosine diphosphate (ADP) (0.011000 pmol) but not adenosine monophosphate (AMP) (0.011000 pmol) induces a similar response in the mesenteric vascular circuit. L-NAME, a nitric oxide synthase inhibitor (200 µM, 30 min), significantly reduces the arterial dilatory effect of ATP and abolishes the responses to ADP and AMP. Complete removal of the endothelium with 3-[(3-cholamidopropyl) dimethylammonio]-1-propansulfonate (CHAPS) (20 mM, 2 × 45 s) abolishes ATP-induced responses. Infusion of ATP in the vascular circuit generated detectable amounts of ADP and AMP, as measured by HPLC. CHAPS treatment significantly reduced the level of ATP and the production of AMP in the arterial mesenteric circuit. In contrast to the arterial mesenteric vasculature, endothelium removal in the venous circuit triggered a marked potentiation of ADP release and, interestingly, a marked reduction in the release of AMP. Moreover, a specific inhibitor of NTP diphosphohydrolase, 1-hydroxynaphthlene-3,6-disulfonic acid BGO 136 (10 mM for 20 min), significatively reduced AMP production in both vascular preparations. These results confirm that the endothelium contributes to the vasoactive properties of ATP, ADP, and AMP. Our data also demonstrated a significant role of endothelium in NTPDase activity on ADP and AMP production prior to exogenous administration of ATP. The activity of this particular enzyme appears to be different from the reaction products viewpoint (i.e., the production of ADP) in the pre- and post-mesenteric circuits, suggesting two different isoforms with different substrate specificities.Key words: ATP, ADP, AMP, NTPDase, mesenteric vasculature.
Modulation of intracellular Ca2+ via L-type calcium channels in heart cells by the autoantibody directed against the second extracellular loop of the α1-adrenoceptors
Authors: Bkaily Ghassan , El-Bizri Nesrine , Bui Michel , Sukarieh Rami , Jacques Danielle , Fu Michael L.X
Published: June 2003

The effects of methoxamine, a selective α1-adrenergic receptor agonist, and the autoantibody directed against the second extracellular loop of α1-adrenoceptors were studied on intracellular free Ca2+ levels using confocal microscopy and ionic currents using the whole-cell patch clamp technique in single cells of 10-day-old embryonic chick and 20-week-old fetal human hearts. We observed that like methoxamine, the autoantibody directed against the second extracellular loop of α1-adrenoreceptors significantly increased the L-type calcium current (ICa(L)) but had no effect on the T-type calcium current (ICa(T)), the delayed outward potassium current, or the fast sodium current. This effect of the autoantibody was prevented by a prestimulation of the receptors with methoxamine and vice versa. Moreover, treating the cells with prazosin, a selective α1-adrenergic receptor antagonist blocked the methoxamine and the autoantibody-induced increase in ICa(L), respectively. In absence of prazosin, both methoxamine and the autoantibody showed a substantial enhancement in the frequency of cell contraction and that of the concomitant cytosolic and nuclear free Ca2+ variations. The subsequent addition of nifedipine, a specific L-type Ca2+ channel blocker, reversed not only the methoxamine or the autoantibody-induced effect but also completely abolished cell contraction. These results demonstrated that functional α1-adrenoceptors exist in both 10-day-old embryonic chick and 20-week-old human fetal hearts and that the autoantibody directed against the second extracellular loop of this type of receptors plays an important role in stimulating their activity via activation of L-type calcium channels. This loop seems to have a functional significance by being the target of α1-receptor agonists like methoxamine.Key words: α1-adrenoceptor, autoantibody, heart cells, calcium, ion channels, confocal microscopy.
Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells
Authors: El-Bizri Nesrine , Bkaily Ghassan , Wang Shimin , Jacques Danielle , Regoli Domenico , D'Orléans-Juste Pedro , Sukarieh Rami
Published: June 2003

Using Fluo-3 calcium dye confocal microscopy and spontaneously contracting embryonic chick heart cells, bradykinin (1010M) was found to induce positive chronotropic effects by increasing the frequency of the transient increase of cytosolic and nuclear free Ca2+. Pretreatment of the cells with either B1or B2receptor antagonists (R126 and R817, respectively) completely prevented bradykinin (BK) induced positive chronotropic effects on spontaneously contracting single heart cells. Using the whole-cell voltage clamp technique and ionic substitution to separate the different ionic current species, our results showed that BK (106M) had no effect on fast Na+inward current and delayed outward potassium current. However, both L- and T-type Ca2+currents were found to be increased by BK in a dose-dependent manner (1010107M). The effects of BK on T- and L-type Ca2+currents were partially blocked by the B1receptor antagonist [Leu8]des-Arg9-BK (R592) (107M) and completely reversed by the B2receptor antagonist D-Arg[Hyp3,D-Phe7,Leu8]BK (R-588) (107M) or pretreatment with pertussis toxin (PTX). These results demonstrate that BK induced a positive chronotropic effect via stimulation of T- and L-type Ca2+currents in heart cells mainly via stimulation of B2receptor coupled to PTX-sensitive G-proteins. The increase of both types of Ca2+current by BK in heart cells may explain the positive inotropic and chronotropic effects of this hormone.Key words: chick heart cells, bradykinin, B1receptor, B2receptor, Ca2+, Na+, K+currents.
Angiotensin II and its receptors in human endocardial endothelial cells: role in modulating intracellular calcium
Authors: Jacques Danielle , Malak Nelly A. Abdel , Sader Sawsan , Perreault Claudine
Published: June 2003

he aims of the present study are to investigate the presence and distribution of angiotensin II (Ang II), as well as AT1and AT2receptors, in endocardial endothelial cells (EECs) and to determine if the effect of Ang II on intracellular calcium in these cells is mediated via the AT1or the AT2receptor. Immunofluorescence and 3D confocal microscopy techniques were used on 20-week-old fetal human EECs. Our results showed that Ang II and its receptors, the AT1and the AT2types, are present and exhibit a different distribution in human EECs. Ang II labelling is found throughout the cell with a fluorescence signal higher in the cytosol when compared with the nucleus. Like Ang II, the AT1receptor fluorescence signal is also homogeneously distributed in human EECs but with a preferential labelling at the level of the nucleus, while the AT2receptor labelling is solely present in the nucleus. Using fluo-3 and 3D confocal microscopy technique, superfusion of human EECs with increasing concentration of Ang II induced a dose-dependent sustained increase in free cytosolic and nuclear Ca2+levels. This effect of Ang II on human EEC's intra cellular Ca2+([Ca2+]i) was completely prevented by losartan, an AT1receptor antagonist. Our results suggest that Ang II, as well as AT1and AT2receptors, is present but differentially distributed in EECs of 20-week-old fetal human hearts, and that the AT1receptor mediates the effects of Ang II on [Ca2+]iin these cells.Key words: angiotensin II, nuclear receptors, endocardial endothelial cells, Ang II receptors, intracellular calcium.
Effect of exercise training on liver antioxidant status of deoxycorticosterone acetate salt induced hypertensive rats
Authors: Elhaïmeur Fatiha , Courderot-Masuyer Carol , Nicod Laurence , Bobillier-Chaumont Sylvie , Robin Sophie , Richert Lysiane , Berthelot Alain
Published: June 2003

Several animal models have been developed to study the pathogenesis of hypertension. Deoxycorticosterone acetate (DOCA) salt induced hypertensive rats are adrenal models used to mimic human Conn's syndrome. Because previous studies showed a beneficial effect of chronic exercise (swimming) on the development of arterial hypertension in spontaneously hypertensive rats (which appears similar to human essential hypertension), we decided to evaluate the effects of swimming on DOCA-salt induced hypertension and liver antioxidant status. Therefore, the aim of this experiment was to study whether the swim training would improve hypertension and liver antioxidant status in DOCA-salt rats. DOCA-salt rats and control SpragueDawley rats were trained to swim 1 h/day, 5 days/week for 6 weeks and were sacrificed 48 h after the last exercise period. Systolic blood pressure was recorded before the sacrifice, and liver antioxidant status was evaluated in hepatic homogenates after the sacrifice. Swim exercise did not decrease systolic blood pressure in control and DOCA-salt rats but induced changes in liver activities of antioxidant enzymes, showing that exercise provoked liver oxidative stress in control and DOCA-salt rats. In comparison with our previous studies using spontaneously hypertensive rats, we conclude that the beneficial effects of chronic exercise on systolic blood pressure in rats are dependent on strain and the type of experimental hypertension.Key words: exercise, DOCA-salt induced hypertensive rats, oxidative stress, liver.
Chronic prenatal ethanol exposure-induced decrease of guinea pig hippocampal CA1 pyramidal cell and cerebellar Purkinje cell density
Authors: McGoey Tara N , Reynolds James N , Brien James F
Published: June 2003

The brain is a key target of ethanol teratogenicity, in which ethanol can produce neurodegeneration in selected areas, including the hippocampus and cerebellum. The research objective was to test the hypothesis that chronic prenatal ethanol exposure, via maternal ethanol administration, produces differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells. Timed pregnant guinea pigs received chronic oral administration of ethanol, isocaloric-sucrose/pair-feeding, or water throughout gestation (term, about gestational day (GD) 68), and the offspring were studied at GD 62 (near-term fetus), postnatal day (PD) 1 (neonate), PD 5, and PD 12 (early postnatal life). Ethanol treatment, compared with isocaloric-sucrose/pair-feeding and water treatments, decreased brain, hippocampal, and cerebellar weights at GD 62, PD 1, PD 5, and PD 12. Hippocampal CA1 pyramidal cell linear density and cerebellar Purkinje cell linear density were unaffected at GD 62. Ethanol treatment produced 25, 30, and 30% decreases in linear density of hippocampal CA1 pyramidal cells at PD 1, PD 5, and PD 12, respectively, and a 30% decrease in linear density of cerebellar Purkinje cells at PD 12 only. At PD 5, Purkinje cell profile linear density remained unaffected; however, ethanol treatment appeared to increase linear density of apoptotic Purkinje cell nuclei, as determined by a modified TUNEL method. The data demonstrate that chronic prenatal ethanol exposure produces apparent differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells in the developing guinea pig.Key words: prenatal ethanol exposure, hippocampal CA1 pyramidal cells, cerebellar Purkinje cells, decreased linear density, differential time course, guinea pig.
Role of endothelins in septic, cardiogenic, and hemorrhagic shock
Authors: Magder S , Cernacek P
Published: June 2003

Shock is a condition where blood flow is inadequate for tissue needs. In all forms of shock, the concentrations of endothelins (ETs) are elevated, and they are especially high in septic shock. The rise in ETs plasma levels may initially have some positive homeostatic effects, for ETs can help restore normal vascular tone. However, high levels of ETs compromise the appropriate matching of flow to tissue needs and contribute to the pathophysiology of shock. Attempts at regulating the effects of ETs by the use of pharmacological blockers is made complicated by important interactions between the ETAand ETBreceptors and potentially different effects on different tissues. We conclude that antagonism of ET receptors is unlikely to be helpful for cardiogenic or hemorrhagic shock. Furthermore, selective blockade is unlikely to be helpful. However, moderate doses of a mixed ET receptor antagonist may be of use for the management of septic patients.Key words: sepsis, endotoxin, cardiac output hypotension, regional blood flows.
Effects of acid-induced esophagitis on esophageal smooth muscle
Authors: Wells R W , Morris G P , Blennerhassett M G , Paterson W G
Published: June 2003

Acid-induced esophagitis is associated with sustained longitudinal smooth muscle (LSM) contraction and consequent esophageal shortening. In addition, LSM strips from opossums with esophagitis are hyper-responsive, while the circular smooth muscle (CSM) contractility is impaired. To determine the origin of these changes, studies were performed on esophageal smooth muscle cells isolated from opossum esophagi perfused intraluminally on 3 consecutive days with either saline (control; n = 8) or HCl (n = 9). CSM and LSM cells, obtained by enzymatic digestion, were exposed to various concentrations of carbachol (CCh) and fixed. CCh induced concentration-dependent contraction of both LSM and CSM cells. CCh-induced LSM cell contraction was not different between control and esophagitis animals; however, there was marked attenuation in the CCh-induced contraction of CSM cells from esophagitis animals. Morphological studies revealed significant hypertrophy of the CSM cells. These findings suggest that impaired CSM contractility can be attributed at least in part to alterations to the CSM cell itself. In contrast, hyper-contractility demonstrated in LSM strips is likely related to factors in the surrounding tissue.Key words: circular, contractility, hypertrophy, longitudinal, smooth muscle cell.
The endothelin system and its role in acute myocardial infarction
Authors: Cernacek Peter , Stewart Duncan J , Monge Juan-Carlos , Rouleau Jean-Lucien
Published: June 2003

Immediately after an acute myocardial infarction (AMI) or in models of ischemia-reperfusion injury, cardiac endothelin (ET) system is markedly activated, and plasma levels of ET are increased. In the heart, expression of the main components of the ET system (ET-1 peptide, both receptor subtypes ETA and ETB, though not endothelin converting enzyme) are increased both at the gene level and protein level, in the viable myocardium, and  even more substantially  in the necrotic area. Despite these conspicuous abnormalities, the role of ET in this setting remains unclear. In the absence of human data, most short-term studies in animals (in terms of hours to up to 8 days post-AMI) and in the reperfused ischemic heart, have found beneficial effects of ET receptor blockade on survival rate, incidence of arrhythmias, cardiac function, and morphology. In contrast, many studies in which a long-term ET inhibition was started immediately post-infarction and the late effects were examined in animals with ensuing chronic heart failure (14100 days postinfarction), adverse effects were also observed, such as scar thinning, further ventricular dilation, or even a worse survival rate. It appears that the ET system plays a dual role during the early post-AMI period. At present, it is not clear whether the short-term beneficial effects or long-term adverse effects of ET receptor blockade would prevail. Acute use of short-acting ET receptor antagonists in patients with AMI complicated by an acute heart failure is an attractive possibility that also remains to be investigated.Key words: endothelin, receptor antagonists, myocardial infarction, heart failure.
Endothelins in chronic diabetic complications
Authors: Khan Zia Ali , Chakrabarti Subrata
Published: June 2003

Endothelins are widely distributed in the body and perform several vascular and nonvascular functions. Experimental data indicate abnormalities of the endothelin system in several organs affected in chronic diabetic complications. In support of this notion, it has been shown that endothelin-receptor antagonists prevent structural and functional abnormalities in target organs of diabetic complications in animal models. Alterations of plasma endothelin levels have also been demonstrated in human diabetes. This review discusses the role of endothelins in the pathogenesis of chronic diabetic complications. The current experimental evidence suggests that endothelin-receptor antagonism may potentially be an adjuvant therapeutic tool in the treatment of chronic diabetic complications.Key words: endothelins, diabetic complications, retinopathy, nephropathy, neuropathy, cardiomyopathy.
A novel vasopressin peptide lowers blood pressure through decreases in cardiac output
Authors: Yu Ming , Ghosh Mahua , McNeill J Robert
Published: June 2003

The changes in blood pressure, cardiac output, and total peripheral conductance evoked by the novel hypotensive arginine vasopressin (AVP) - like peptide, d(CH2)5[D-Tyr(Et)2,Arg3,Val4,Arg7,Eda9]AVP (HYPO-AVP), were recorded in conscious unrestrained SpragueDawley rats implanted with radiotelemetry pressure transducers and ultrasonic transit-time flowprobes. Intravenous infusions of 0.6, 1.0, 2.0, and 4.0 μg·kg1·min1 of HYPO-AVP evoked dose-related decreases in blood pressure. At the lowest dose of 0.6 μg·kg1·min1, the fall in blood pressure was associated with a small but significant increase in total peripheral conductance. Cardiac output was unchanged. In contrast, at the three higher doses of 1.0, 2.0, and 4.0 μg·kg1·min1, the fall in blood pressure was related to a dramatic fall in cardiac output. Indeed, total peripheral conductance decreased, preventing blood pressure from falling further. These hemo dynamic findings should help to direct future research into the mechanism of the putative hypotensive property of vaso pressin, a property that attenuates the well established blood pressure elevating actions of the peptide.Key words: vasopressin, blood pressure, cardiac output, total peripheral resistance, hypotensive peptide.
Effects of cannabinoids on endogenous K+ and Ca2+ currents in HEK293 cells
Authors: Vásquez Clemente , Navarro-Polanco Ricardo A , Huerta Miguel , Trujillo Xóchitl , Andrade Felipa , Trujillo-Hernández Benjamín , Hernández Leonardo
Published: June 2003

Effects of cannabinoids on endogenous potassium and calcium currents in HEK293 cells were studied using the whole-cell variant of the patch-clamp technique. The cannabinoid agonists WIN 55,212-2, methanandamide, and anandamide (1 μM) decreased the calcium current by 53.1 ± 2.6, 47.5 ± 1.2, and 38.8 ± 3.1%, respectively, after transfection of human CB1 cannabinoid receptor (hCB1) cDNA into HEK293 cells. The delayed rectifier-like current was not changed after application of these agonists, but the inward rectifier was increased by 94.0 ± 3.6, 83.7 ± 5.1, and 63.0 ± 2.5% after application of WIN 55,212-2, methanandamide, and anandamide, respectively. The effects of the cannabinoid antagonists (AM251, AM281, and AM630) on the inward rectifier and calcium currents were the opposite of those seen with cannabinoid agonists; thus, these compounds act as inverse agonists in this preparation. These results suggest that endogenous inward rectifier and calcium currents are modulated by cannabinoids in HEK293 cells, and that some expressed receptors may be constitutively active.Key words: cannabinoids, WIN 55,212-2, anandamide, methanandamide, inverse agonists.
The β-adrenoceptor site activated by CGP12177 varies in behavior according to the estrous cycle phase and stress
Authors: Santos I N , Marcondes F K , Spadari-Bratfisch R C
Published: June 2003

The aim of this work was to assess whether stress and estrous cycle phases affected the β-adrenoceptor (β-AR) site activated by CGP12177 in the right atria of rats. The chronotropic response to CGP12177 in the absence or presence of antagonists was determined in atria from rats submitted to one daily foot-shock session for 3 consecutive days. Blood was collected for hormonal assays. The pD2 for CGP12177 in atria from females was lower than in atria from males and was unaltered by stress or the estrous cycle. Propranolol (200 nM) or CGP20712A (3 μM) shifted the concentrationresponse curves to CGP12177 to the right in control and stressed estrus or control diestrus rats. Atria from stressed diestrus rats were resistant to blockade by propranolol or CGP20712A, indicating that the effect of β-adrenoceptor antagonists on the response to CGP12177 is influenced by estrous cycle phases. The stress-induced increase in serum corticosterone levels was independent of the estrous cycle or gender, but the estradiol/progesterone ratio was affected differently in the two groups of female rats. In the diestrus group, serum estradiol levels decreased after the first foot-shock session and remained low until the day of sacrifice, whereas in the estrus group the serum levels of estradiol did not decrease after stress and peaked on the second day, which corresponded to proestrus. These data do not indicate whether there is a direct or indirect effect of stress hormones and (or) sex steroids on cardiac β-AR sensitivity. However, they do show that the classic and low-affinity binding sites of the β-AR are independently regulated and that the β-AR atypical site affinity for antagonists depends on the estrous cycle.Key words: allosterism, β-adrenoceptor, β-adrenoceptor, receptor active site, steroid hormones, stress.