Corrigendum to: Effects of L-arginine on endothelial and cardiac function in rats with heart failure
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Journal Article↗
Biomedical subjects
Q Feng
Publications and source records attributed to Q Feng.
Effects of L-arginine on endothelial and cardiac function in rats with heart failure.
We examined the effects of chronic oral L-arginine treatment on endothelial and cardiovascular function in rats with heart failure induced by coronary artery ligation. Both heart failure and sham-operated rats were treated with either L-arginine in drinking water (12.5 or 50 g/l) or water placebo for 8 weeks following surgery. Plasma L-arginine levels in heart failure rats (153 +/- 11 microM) were lower than sham rats (201 +/- 13 microM, P < 0.05). The lower dose L-arginine treatment improved endothelium-dependent relaxation of isolated aortic rings of heart failure rats, while the higher dose of L-arginine treatment did not. Neither low nor high dose of L-arginine treatment improved hemodynamic parameters in heart failure rats. Thus, chronic oral L-arginine treatment at a dose of 12.5 g/l in drinking water improves endothelium-dependent relaxation, but fails to improve in vivo cardiac function in rats with heart failure.
Animals↗
Decreased responsiveness of vascular postjunctional alpha1-, alpha2-adrenoceptors and neuropeptide Y1 receptors in rats with heart failure.
Heart failure is associated with increased sympathetic nerve activity. We hypothesized that chronic sympathetic stimulation in heart failure resulted in decreased vascular sympathetic responsiveness. A pithed rat model was employed to evaluate peripheral vascular alpha-adrenoceptor and neuropeptide Y (NPY) receptor responsiveness. Heart failure was induced in Sprague-Dawley rats by coronary artery ligation. Sham operated rats (Sham) served as controls. Two months after this surgical procedure, both heart failure (n = 30) and Sham (n = 30) rats underwent standard pithing procedure. Pressor responses to preganglionic sympathetic nerve stimulation (PNS) and activation of postjunctional alpha1- and alpha2-adrenoceptors as well as Y1 receptors were studied. In response to PNS, cardiac index was similar between heart failure and sham rats (P = n.s.). Mean arterial pressure (MAP) increased in a frequency-dependent fashion after PNS in heart failure rats as well as in control rats. All the agonists used, i.e. the alpha1-adrenoceptor agonist phenylephrine, the alpha2-adrenoceptor agonists clonidine and BHT933 as well as NPY, induced dose-dependent increases in MAP in heart failure and in sham rats. However, in rats with heart failure, the response to all the agonists studied was significantly decreased and the dose response curves were shifted to the right (P < 0.01). We conclude that in vivo vascular response to postjunctional alpha1- and alpha2-adrenoceptors as well as Y1 receptors are decreased in rats with heart failure.
Adrenergic alpha-Agonists↗
Expression of tissue type and urokinase type plasminogen activators as well as plasminogen activator inhibitor type-1 and type-2 in human and rhesus monkey placenta.
The distribution of mRNAs and antigens of tissue type (t) and urokinase type (u) plasminogen activators (PA) plus their corresponding inhibitors, type-1 (PAI-1) and type-2 (PAI-2) were studied in human and rhesus monkey placentae by in situ hybridisation and immunocytochemistry. Specific monkey cRNA and antibodies against human tPA, uPA, PAI-1 and PAI-2 were used as probes. The following results were obtained. (1) All the molecules tPA, uPA, PAI-1 and PAI-2 and their mRNAs were identified in the majority of the extravillous cytotrophoblast cells of the decidual layer between Rohr's and Nitabuch's striae and in cytotrophoblast cells of the chorionic plate, basal plate, intercotyledonary septae and cytotrophoblast cells of the chorionic villous tree. (2) Expression of uPA and PAI-2 was noted in villous trophoblast whereas tPA and PAI-1 were mainly concentrated where detachment from maternal tissue occurs. (3) No expression of tPA, uPA, PAI-1 and PAI-2 was observed in the basal plate endometrial stromal cells, chorionic plate connective tissue cells, septal endometrial stromal cells or villous core mesenchyme. (4) The distribution of probes observed following in situ hybridisation is generally consistent with the immunofluorescence pattern of the corresponding antigens and no significant interspecies differences were noted. It is possible that both decidual and extravillous trophoblast cells of placentae of human and rhesus monkey are capable of producing tPA, uPA, PAI-1 and PAI-2 to differing extents. Coordinated expression of these genes in the tissue may play an essential role in the maintenance of normal placentation and parturition. The differences in distribution we observed are consistent with the suggestion that coordinated expression of tPA and its inhibitor PAI-1 may play a key role in fibrinolytic activity in the early stages of placentation and separation of placenta from maternal tissue at term. On the other hand, uPA with its inhibitor PAI-2 appears mainly to play a role in degradation of trophoblast cell-associated extracellular matrix, and thus may be of greatest importance during early stages of placentation.
Animals↗
Expression of the steroidogenic acute regulatory protein and luteinizing hormone receptor and their regulation by tumor necrosis factor alpha in rat corpora lutea.
Expression of both mRNA and protein of the steroidogenic acute regulatory protein (StAR), in correlation with progesterone (P) production and LH receptor (LHR) mRNA expression, was studied in the corpora lutea (CL) of gonadotropin-induced-pseudopregnant and pregnant rats at various stages of CL development. Immature female rats, 21-22 days old, were injected s.c. with 20 IU eCG to stimulate follicle growth and then with 20 IU hCG 48 h later to induce ovulation. The ovaries were removed at various stages of CL development; either CL were isolated and snap frozen for total RNA analysis, or whole ovaries were fixed in Bouin's fluid for paraffin sectioning. The results of in situ hybridization, immunohistochemistry, and Northern blotting showed that the increase in StAR mRNA and protein expression was well correlated with the increase in serum P concentration. StAR expression was restricted to the luteal cells or theca cells in antral follicles. Both StAR mRNA and protein in the CL of pseudopregnant rats increased steadily on Day 1 and Day 4, reached highest levels on Day 4, and then dropped sharply on Day 8 when luteolysis takes place. LHR mRNA content was high on Day 1 but dropped significantly on Day 2. LHR mRNA increased to high levels on Day 4 and 8 and then declined on Day 12. StAR mRNA and protein levels in the CL of pregnant rats were high during early luteal development (Day 2, 4), increased even further on Day 9, and decreased on Day 13 when luteolysis takes place. It is therefore suggested that the expression of StAR coincides well with the capacity of P production in the CL and that StAR expression can be used as a functional "marker" of CL development. To study the possible effect of cytokines on StAR expression, pseudopregnant rats on Day 5 were injected s.c. with 10 IU hCG plus 20 microg prolactin (PRL), with or without 500 IU tumor necrosis factor alpha (TNFalpha) 30 min later. TNFalpha significantly inhibited hCG/PRL-induced StAR and LHR mRNA expression at 1 and 3 h post-TNFalpha. It is suggested that the luteolytic effect of TNFalpha may be mediated by its direct inhibition on StAR expression or by an indirect decrease in LHR expression.
Animals↗
Ras signaling is required for serum-induced hyphal differentiation in Candida albicans.
Serum induces Candida albicans to make a rapid morphological change from the yeast cell form to hyphae. Contrary to the previous reports, we found that serum albumin does not play a critical role in this morphological change. Instead, a filtrate (molecular mass, <1 kDa) devoid of serum albumin induces hyphae. To study genes controlling this response, we have isolated the RAS1 gene from C. albicans by complementation. The Candida Ras1 protein, like Ras1 and Ras2 of Saccharomyces cerevisiae, has a long C-terminal extension. Although RAS1 appears to be the only RAS gene present in the C. albicans genome, strains homozygous for a deletion of RAS1 (ras1-2/ras1-3) are viable. The Candida ras1-2/ras1-3 mutant fails to form germ tubes and hyphae in response to serum or to a serum filtrate but does form pseudohyphae. Moreover, strains expressing the dominant active RAS1(V13) allele manifest enhanced hyphal growth, whereas those expressing a dominant negative RAS1(A16) allele show reduced hyphal growth. These data show that low-molecular-weight molecules in serum induce hyphal differentiation in C. albicans through a Ras-mediated signal transduction pathway.
Amino Acid Sequence↗
Orally administered NHE1 inhibitor cariporide reduces acute responses to coronary occlusion and reperfusion.
Na+/H+ exchange (NHE) mediates myocardial ischemic and reperfusion injury. We examined the effects of dietary administration of the potent and selective NHE1 inhibitor cariporide on acute responses to coronary artery ligation and reperfusion in the anesthetized rat. Male Sprague-Dawley rats received control rat chow or an identical diet containing 3 parts per million of cariporide for 1 wk before 225 min of occlusion of the left main coronary artery or 45 min of occlusion followed by 180 min of reperfusion. Hearts were excised and divided into left ventricle, right ventricle, and interventricular septum for analysis of NHE1 mRNA expression and apoptosis by staining with terminal deoxynucleotidyl transferase-mediated nick end labeling. Ischemia and reperfusion were associated with a threefold elevation in NHE1 mRNA expression in control animals that was significantly reduced in cariporide-fed rats. Cariporide reduced mortality from 26% of animals to 0%. The incidence of all arrhythmias was significantly reduced, including ventricular fibrillation (from 42 to 0%) and ventricular tachycardia (from 81 to 15%), as well as the number of ventricular premature beats (from 70 +/- 12 to 17 +/- 6). Cariporide moderately reduced apoptosis only in the reperfused left ventricle to values not significantly greater than those in sham-operated animals, and this was associated with a significantly higher ratio of Bcl-2 to Bax. This study suggests that NHE inhibition with dietary cariporide represents an effective management of acute postinfarction responses.
Administration, Oral↗
[Construction and expression of HLA-DRalpha, DRB1*0401 transgenic mice model].
OBJECTIVE: To construct transgenic mice model on DR alpha and DRB1*0401 of human MHC-II molecules. METHODS: By microinjection techniques on germ nucleus of zygotes, DRalpha and DRB1*0401 genes were injected into zygotes of C57BL/6 x DBA/1 hybrid mice and transplanted into the oviducts of pseudopregnancy female mice. The integration and expression of exogenous genes in offspring were detected by PCR, Southern blot and Northern blot, RT-PCR analysis. RESULTS: There were 5 founders of all injected mice, which had steadily inherited to the fifth generation. It was found that 95 mice were positive by PCR and 68 mice were integrated exogenous gene by Southern blot analysis. DRalpha and DRB1*0401 genes were expressed on spleen and kidney of transgenic mice. CONCLUSION: This experiment on the construction of DRalpha and DRB1*0401 transgenic mice model is a success.
Animals↗
Predictive action in infancy: tracking and reaching for moving objects.
Because action plans must anticipate the states of the world which will be obtained when the actions take place, effective actions depend on predictions. The present experiments begin to explore the principles underlying early-developing predictions of object motion, by focusing on 6-month-old infants' head tracking and reaching for moving objects. Infants were presented with an object that moved into reaching space on four trajectories: two linear trajectories that intersected at the center of a display and two trajectories containing a sudden turn at the point of intersection. In two studies, infants' tracking and reaching provided evidence for an extrapolation of the object motion on linear paths, in accord with the principle of inertia. This tendency was remarkably resistant to counter-evidence, for it was observed even after repeated presentations of an object that violated the principle of inertia by spontaneously stopping and then moving in a new direction. In contrast to the present findings, infants fail to extrapolate linear object motion in preferential looking experiments, suggesting that early-developing knowledge of object motion, like mature knowledge, is embedded in multiple systems of representation.
Child Development↗
Retrotransposon R1Bm endonuclease cleaves the target sequence.
The R1Bm element, found in the silkworm Bombyx mori, is a member of a group of widely distributed retrotransposons that lack long terminal repeats. Some of these elements are highly sequence-specific and others, like the human L1 sequence, are less so. The majority of R1Bm elements are associated with ribosomal DNA (rDNA). R1Bm inserts into 28S rDNA at a specific sequence; after insertion it is flanked by a specific 14-bp target site duplication of the 28S rDNA. The basis for this sequence specificity is unknown. We show that R1Bm encodes an enzyme related to the endonuclease found in the human L1 retrotransposon and also to the apurinic/apyrimidinic endonucleases. We expressed and purified the enzyme from bacteria and showed that it cleaves in vitro precisely at the positions in rDNA corresponding to the boundaries of the 14-bp target site duplication. We conclude that the function of the retrotransposon endonucleases is to define and cleave target site DNA.
Amino Acid Sequence↗
Overexpression of protein kinase C alpha enhances lipopolysaccharide-induced nitric oxide formation in vascular smooth muscle cells.
Our previous studies showed that lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis in cardiovascular tissues is attenuated by protein kinase C (PKC) inhibitors. In the current study, we identify a specific PKC isotype involved in the LPS signal transduction pathway that leads to NO formation in rat vascular smooth muscle cells (VSMC). VSMC were transfected with a mammalian expression vector containing a full length PKCalpha cDNA insert, and a stable transfectant overexpressing PKCalpha was obtained as evidenced by increased expression of PKCalpha mRNA and protein. In response to 100 ng/ml LPS stimulation, the PKCalpha transfectants showed a 1.8-fold increase in PKC activity at 30 min and a twofold increase in NO production over 24 hr compared with cells transfected with control plasmids. The LPS-stimulated increase in NO synthesis in PKCalpha transfectants was blocked by the specific PKCalpha inhibitor Gö 6976. After 6 hr LPS treatment, PKCalpha-transfected and control cells showed equivalent increases in mRNA and protein for the inducible NO synthase. NO synthase activity of the cell extracts assayed in the presence of excess substrate and cofactors was not significantly different between PKCalpha-transfected and control cells after LPS stimulation. However, mRNA levels for GTP cyclohydrolase I, a key enzyme in (6R)-tetrahydro-L-biopterin synthesis, and cationic amino acid transporter-2, involved in L-arginine transport, was enhanced in cells overexpressing PKCalpha compared with control cells. These results suggest that PKCalpha plays an important role in LPS-induced NO formation and that a significant portion of this effect may be by means of enhanced substrate availability to the inducible nitric oxide synthase enzyme.
Amino Acid Transport Systems, Basic↗
Elevation of an endogenous inhibitor of nitric oxide synthesis in experimental congestive heart failure.
OBJECTIVE: NG,NG-dimethylarginine (asymmetric dimethylarginine, ADMA) is an important endogenous substance with potent inhibitory actions on nitric oxide (NO) synthesis. The present study was designed to determine circulating ADMA levels and endothelium-dependent, NO mediated vasodilation in a rat model of congestive heart failure (CHF). METHODS: CHF was induced in rats by coronary artery ligation. Sham-operated rats served as normal controls. Plasma ADMA was determined by high performance liquid chromatography with fluorescence detection. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by the clearance of inulin and p-aminohippuric acid, respectively. Endothelial function of the aorta was assessed in an organ bath. RESULTS: Plasma levels of ADMA in rats with CHF (0.94 +/- 0.05 mumol/l) were significantly increased compared with sham-operated controls (0.75 +/- 0.06 mumol/l, p < 0.05). Plasma levels of ADMA was negatively correlated with GFR (r = -0.65, p < 0.05). Decreased endothelium-dependent relaxation to acetylcholine in the aorta of CHF was completely restored by L-arginine (300 microM) (p < 0.01) while endothelium-independent relaxation to nitroprusside was not altered. ADMA potently inhibited endothelium-dependent relaxation in thoracic aorta of normal and CHF rats. The effect of ADMA was completely antagonized by L-arginine in both groups (p < 0.01). Moreover, L-arginine improved endothelium-dependent relaxation in CHF rats in the presence of ADMA. CONCLUSIONS: An endogenous NO synthesis inhibitor ADMA is increased in the circulation of rats with CHF. The increased plasma levels of ADMA may contribute to the decreased endothelium-dependent relaxation in CHF, which is restored by L-arginine, possibly by competitive antagonism of ADMA.
Acetylcholine↗
Enhanced in vivo alpha1- and alpha2-adrenoceptor-mediated venoconstriction with indomethacin in humans.
Vasodilator prostaglandins are released in vitro from endothelium during adrenergic stimulation. We hypothesized that indomethacin would block this production in vivo and increase venoconstriction to alpha1- and alpha2-stimulation but not to the nonadrenergic agonist PGF2alpha. Hand vein distension was measured in 24 normal subjects (23.0 +/- 0.5 yr) during local infusions of phenylephrine (8-12,000 ng/min), clonidine (3-7,000 ng/min), or PGF2alpha (1-2,048 ng/min) plus indomethacin (3 microg/min) versus saline on two separate days. Dose-dependent venoconstriction to phenylephrine occurred in all subjects, with a parallel shift to the left with indomethacin (P = 0. 003) and a decrease in the phenylephrine 50% effective dose (1,009 vs. 241 ng/min, geometric means, P = 0.012). Venoconstriction to clonidine was more variable, with most subjects eliciting a biphasic response (initial venoconstriction followed by attenuation). With indomethacin, the dose-response curve was displaced up and to the left (P = 0.005), and peak venoconstriction was increased (51.1 +/- 6.8 vs. 27.2 +/- 5.3% of control, P = 0.018) without a biphasic response. In all subjects, PGF2alpha elicited dose-dependent venoconstriction that was not altered by indomethacin. Thus venous alpha1- and alpha2-stimulation results in release of vasodilator prostaglandins that antagonize the venoconstrictor response. This modulates the sympathetic response of venous smooth muscle and may be important in diseases with endothelial dysfunction.
Adrenergic alpha-Agonists↗
Trace element contents in hair of residents from Harbin (China), Medan (Indonesia), and Tokushima (Japan).
The concentrations of 19 trace element in hair samples from 1273 residents of Harbin (China), Medan (Indonesia), and Tokushima (Japan) were measured by inductively coupled plasma emission spectrometry. The mean concentrations of Ba, Ca, and Se were significantly higher in the Harbin hair samples when compared to those from Medan, but Al, B, Cu, Fe, Mn, Na, Pb, Ti, Zn, and K were significantly higher in Medan than in Harbin hair samples. The differences in the mean concentrations of As, Cr, Mg, P, Sn, and Sr between the Medan and Harbin lots were not significant. In the Tokushima hair samples, Na and K were significantly higher, but As, B, Ba, Ca, Cr, Mg, Mn, Pb, Sn, Sr, and Se were significantly lower than in the Harbin hair samples. The differences in the mean concentrations of Al, Cu, Fe, P, Ti, and Zn between Harbin and Tokushima were not significant. In the Medan hair samples, Al, As, B, Ba, Ca, Cr, Cu, Fe, Mg, Mn, Pb, Sn, Sr, Ti, and Zn were significantly higher, but P and Se were significantly lower than in Tokushima hair samples. Differences in mean concentrations of Na and K between Tokushima and Medan were not significant.
Adult↗
Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition.
Human L1 elements are highly abundant poly(A) (non-LTR) retrotransposons whose second open reading frame (ORF2) encodes a reverse transcriptase (RT). We have identified an endonuclease (EN) domain at the L1 ORF2 N-terminus that is highly conserved among poly(A) retrotransposons and resembles the apurinic/apyrimidinic (AP) endonucleases. Purified L1 EN protein (L1 ENp) makes 5'-PO4, 3'-OH nicks in supercoiled plasmids, shows no preference for AP sites, and preferentially cleaves sequences resembling L1 in vivo target sequences. Mutations in conserved amino acid residues of L1 EN abolish its nicking activity and eliminate L1 retrotransposition. We propose that L1 EN cleaves the target site for L1 insertion and primes reverse transcription.
Amino Acid Sequence↗
Birgeneau et al. Reply.
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Journal Article↗
[The effects of propylthiouracil on the fetal thyroid and serum concentration in pregnant women].
In order to study the effects of propylthiouracil (PTU) on the fetal thyroid and serum concentration, 9 women undergoing therapeutic abortion at the second trimester of pregnancy were given a single dose of 50, 100 and 150 mg PTU respectively. The concentrations of PTU in the maternal and fetal serum and those in the fetal thyroid tissues were determined with a high-performance liquid chromatographic method, the lowest limit of which was 25 micrograms/L. After an oral bolus of PTU, the PTU concentrations in the maternal serum reached a peak level after one hour and there was a wide individual variation of the peak value. The study showed PTU could be transferred through the placenta from the maternal blood to the fetal blood and highly accumulated in the fetal thyroid tissues. The fetal serum PTU concentrations correlated with those of their mothers at the same time (r = 0.7084, P < 0.02) and the concentrations in the fetal thyroid tissues could be evaluated by the maternal serum peak level after an oral bolus. PTU didn't inhibit the fetal thyroid peroxidase activity even when the maternal serum PTU concentration reached 4 mg/L, which is the lowest effective therapeutic concentration of PTU in adults.
Adult↗