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Increased Release (increased + release)
Selected AbstractsActivation of PLA2 isoforms by cell swelling and ischaemia/hypoxiaACTA PHYSIOLOGICA, Issue 1-2 2006I. H. Lambert Abstract Phospholipase A2 (PLA2) activity is increased in mammalian cells in response to numerous stimuli such as osmotic challenge, oxidative stress and exposure to allergens. The increased PLA2 activity is seen as an increased release of free, polyunsaturated fatty acids, e.g. arachidonic acid and membrane-bound lysophospholipids. Even though arachidonic acid acts as a second messenger in its own most mammalian cells seem to rely on oxidation of the fatty acid into highly potent second messengers via, e.g. cytochrome P450, the cyclo-oxygenase, or the lipoxygenase systems for downstream signalling. Here, we review data that illustrates that stress-induced PLA2 activity involves various PLA2 subtypes and that the PLA2 in question is determined by the cell type and the physiological stress condition. [source] Adrenomedullin and diabetes mellitusDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2001Eva Ruzicska Abstract Adrenomedullin (AM) is a novel 52 amino acid peptide hormone, originally isolated from human pheochromocytoma. AM acts as a local autocrine and/or paracrine vasoactive hormone and has vasodilator and blood pressure lowering properties. AM as a vasodilative molecule protects the vascular wall but its exact role is still uncertain. AM is considered to play an important endocrine role in various tissues in maintaining electrolyte and fluid homeostasis. Its plasma concentration in healthy conditions is low. In hypertension, chronic renal failure and congestive heart failure its plasma concentration increases in a parallel manner with the severity of the disease. It is assumed that this peptide plays an important role in physiological and pathological conditions compensating the effects of vasoconstrictive molecules. Investigations have proven that in diabetic angiopathies the levels and production of vasoconstrictive factors and AM are increased, while other relaxing substances such as nitric oxide (NO) are decreased. It is still uncertain whether the increased release of AM is a compensatory mechanism or a coincidental event. Although the precise role of AM in the pathogenesis of diabetic complications is still to be elucidated, the altered concentration of AM in diabetes could indicate a certain interaction between AM induction and vascular function. Hence, the induction of vascular AM can be a new target of therapeutic approach to diabetic complications. Copyright © 2001 John Wiley & Sons, Ltd. [source] Effects of serotonin and catecholamine depletion on interleukin-6 activation and mood in human volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2002Ben J. Harrison Abstract There is increasing evidence that depression and related neurotic illnesses are associated with alterations in immune function that may contribute to their pathogenesis. For example, clinical and experimental studies have shown that abnormal HPA-axis activation and monoamine neurotransmission may be related to an increased release of proinflammatory cytokines from stimulated lymphocytes in the periphery and brain. In the present investigation, the effects of tryptophan depletion (TD) on unstimulated plasma interleukin-6 (IL-6) concentrations were investigated in order to determine whether acute changes in serotonin (5-HT) neurotransmission would induce a proinflammatory response in healthy individuals. The effects of TD were compared with the analogous procedure of tyrosine depletion (TPD), which reduces catecholamine metabolism in humans. Thirteen female participants completed three experimental sessions: TD, TPD and a balanced-control condition (B). Mood-ratings and blood sampling were performed at baseline and 5,h after the administration of the mixtures. Analyses revealed that TD and TPD markedly reduced tryptophan and tyrosine/phenylalanine levels, respectively. No changes in plasma IL-6 production or ratings of lowered mood were observed, however, subjects did report feeling more fatigued after TD. These findings indicate that a transient disruption in global monoamine function does not stimulate a proinflammatory response of IL-6 in normal volunteers. Copyright © 2002 John Wiley & Sons, Ltd. [source] Immortalized cell lines from mouse xiphisternum preserve chondrocyte phenotypeJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2006Manas K. Majumdar Chondrocytes are unique to cartilage and the study of these cells in vitro is important for advancing our understanding of the role of these cells in normal homeostasis and disease including osteoarthritis (OA). As there are limitations to the culture of primary chondrocytes, cell lines have been developed to overcome some of these obstacles. In this study, we developed a procedure to immortalize and characterize chondrocyte cell lines from mouse xiphisternum. The cells displayed a polygonal to fibroblastic morphology in monolayer culture. Gene expression studies using quantitative PCR showed that the cell lines responded to bone morphogenetic protein 2 (BMP-2) by increased expression of matrix molecules, aggrecan, and type II collagen together with transcriptional factor, Sox9. Stimulation by IL-1 results in the increased expression of catabolic effectors including MMP-13, nitric oxide synthase, ADAMTS4, and ADAMTS5. Cells cultured in alginate responded to BMP-2 by increased synthesis of proteoglycan (PG), a major matrix molecule of cartilage. IL-1 treatment of cells in alginate results in increased release of PG into the conditioned media. Further analysis of the media showed the presence of Aggrecanase-cleaved aggrecan fragments, a signature of matrix degradation. These results show that the xiphisternum chondrocyte cell lines preserve their chondrocyte phenotype cultured in either monolayer or 3-dimensional alginate bead culture systems. In summary, this study describes the establishment of chondrocyte cell lines from the mouse xiphisternum that may be useful as a surrogate model system to understand chondrocyte biology and to shed light on the underlying mechanism of pathogenesis in OA. J. Cell. Physiol. 209: 551,559, 2006. © 2006 Wiley-Liss, Inc. [source] Cold-induced Glutamate Release in vivo from the Magnocellular Region of the Paraventricular Nucleus is Involved in Ovarian Sympathetic ActivationJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2010P. Jara We previously reported that centrally-induced sympathetic activation in response to cold stress is associated with a polycystic ovarian condition in rats, and thyrotrophin-releasing hormone (TRH) released locally from the magnocellular region of the paraventricular nucleus (PVN) appears to be involved in this activation. Because TRH neurones express NMDA glutamate receptors, in the present study, we investigated the role of glutamate in the increased release of TRH from magnocellular neurones induced by cold stress and its relationship to ovarian neurotransmission. Animals with a push,pull cannula stereotaxically implanted into the magnocellular portion of the PVN were exposed to cold stress (4 °C for 64 h) and subjected to intracerebral perfusion. Perfusate fractions were obtained and analysed by high-performance liquid chromatography to measure glutamate and GABA levels. Glutamate, but not GABA, release increased significantly in animals perfused under cold exposure. In vivo administration of glutamate to the PVN increased TRH release. Injection of MK-801 into the magnocellular portion of the PVN reduced ovarian noradrenaline turnover and led to an increase in catecholamine concentration from the adrenal glands and celiac ganglia. Taken together, the results obtained in the present study strongly suggest that glutamate release from the magnocellular PVN is sensitive to cold stress and that glutamate acts through the NMDA receptor to mediate cold-induced TRH release. This in turn triggers hypothalamic-ovarian pathway activation, which might be responsible for the polycystic condition induced by cold stress and other ovarian pathologies characterised by increased sympathetic discharge. [source] Competing Presynaptic and Postsynaptic Effects of Ethanol on Cerebellar Purkinje NeuronsALCOHOLISM, Issue 8 2006Zhen Ming Background: Ethanol has actions on cerebellar Purkinje neurons that can result either in a net excitation or in inhibition of neuronal activity. The present study examines the interplay of presynaptic and postsynaptic mechanisms to determine the net effect of ethanol on the neuronal firing rate of cerebellar Purkinje neurons. Methods: Whole-cell voltage-clamp recording of miniature inhibitory postsynaptic currents (mIPSCs) from Purkinje neurons in cerebellar slices was used to examine the effect of ethanol on presynapticsynaptic release of , -aminobutyric acid (GABA) and glutamate. Extracellular recording was used to examine the net action of both presynaptic and postsynaptic effects of ethanol on the firing rate of Purkinje neurons. Results: Under whole-cell voltage clamp, the frequency of bicuculline-sensitive miniature postsynaptic currents (mIPSCs) was increased dose-dependently by 25, 50, and 100 mM ethanol without any change in amplitude or decay time. Despite this evidence of increased release of GABA by ethanol, application of 50 mM ethanol caused an increase in firing in some neurons and a decrease in firing in others with a nonrandom distribution. When both glutamatergic and GABAergic influences were removed by simultaneous application of 6-cyano-7-nitroquinoxaline-2,3-dione and picrotoxin, respectively, ethanol caused only an increase in firing rate. Conclusions: These data are consistent with a dual action of ethanol on cerebellar Purkinje neuron activity. Specifically, ethanol acts presynaptically to increase inhibition by release of GABA, while simultaneously acting postsynaptically to increase intrinsic excitatory drive. [source] Ethanol Modulation of TNF-alpha Biosynthesis and Signaling in Endothelial Cells: Synergistic Augmentation of TNF-alpha Mediated Endothelial Cell Dysfunctions by Chronic EthanolALCOHOLISM, Issue 6 2005Corinne Luedemann Despite reported cardio-protective effects of low alcohol intake, chronic alcoholism remains a risk factor in the pathogenesis of coronary artery disease. Dose related bimodal effects of alcohol on cardiovascular system might reflect contrasting influences of light versus heavy alcohol consumption on the vascular endothelium. Chronic ethanol induced damage to various organs has been linked to the increased release of TNF-alpha (TNF). We have previously shown that TNF, expressed at the sites of arterial injury, suppresses re-endothelialization of denuded arteries and inhibits endothelial cell (EC) proliferation in vitro. Here we report that in vitro chronic ethanol exposure enhances agonist-induced TNF mRNA and protein expression in EC. Ethanol-mediated increment in TNF expression involves increased de novo transcription without affecting mRNA stability. DNA binding assays revealed that ethanol-induced TNF up regulation was AP1 dependent. Functionally, TNF induced EC dysfunction, including reduced proliferation, migration and cyclin A expression, were all markedly enhanced in the presence of ethanol. Additionally, expression of cyclin D1 was significantly attenuated in cells co-treated with TNF and ethanol while each treatment alone had little effect on cyclin D1 expression. Furthermore, exposure to ethanol potentiated and prolonged agonist-induced activation of JNK. Inhibition of JNK by over-expression of dominant negative JNK1 substantially reversed ethanol/TNF-mediated inhibition of cyclin A expression and EC proliferation, suggesting modulation of JNK1 signaling as the mechanism for ethanol/TNF-induced EC dysfunctions. Taken together, these data indicate that chronic ethanol consumption may negatively influence post angioplasty re-endothelialization thereby contributing to the development of restenosis. [source] Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5-HT4 receptor agonistNEUROGASTROENTEROLOGY & MOTILITY, Issue 11 2009K. Campbell-dittmeyer Abstract, Increased cholinergic stimulation and accelerated gastrointestinal (GI) transit may be produced by direct stimulation of the acetylcholine (ACh) receptor with an appropriate agonist by increased release of ACh from cholinergic nerve terminals or by a decreased removal or breakdown of ACh within cholinergic synapses. The acetylcholinesterase inhibitor, neostigmine, and the 5-HT4 receptor partial agonist tegaserod, are two agents with known prokinetic activity which work by different mechanisms that result in increased levels of ACh at cholinergic synapses innervating intestinal smooth muscle. Here, we aimed to investigate the potential synergistic effect on colonic transit that may occur with concomitant use of these two agents. Colonic transit was indirectly assessed in rats via measurements of fecal pellet output every 30 min for 2.5 h following administration of neostigmine (0.003,0.1 mg kg,1, i.p.), tegaserod (0.01,1.0 mg kg,1, i.p.), or a combination of both compounds. When administered alone, neostigmine or tegaserod caused a dose-dependent increase in fecal pellet output. In combination, low doses of the two agents which did not produce statistically significant effects alone, compared to the vehicle, caused a significant increase in fecal pellet output. Combinations of higher doses of neostigmine and tegaserod did not display synergy. In summary, when combined at low doses, neostigmine and tegaserod produce synergistic effects manifested by a statistically significant increase in the expulsion of fecal pellets. A combination of an anticholinesterase agent with a 5-HT4 receptor agonist may prove to be a useful therapeutic approach to treat conditions associated with slow GI transit. [source] Enhanced protection by melatonin and meloxicam combination in experimental infection by Trypanosoma cruziPARASITE IMMUNOLOGY, Issue 4 2010L. G. R. OLIVEIRA Summary The aim of this study was to evaluate a possible synergism between melatonin and meloxicam in up-regulating the immune response in male Wistar rats infected with Trypanosoma cruzi during immunosuppression phenomenon, which characterizes the acute phase of the Chagas' disease. Male Wistar rats were infected with the Y strain of T. cruzi. Experiments were performed on 7, 14 and 21 days post-infection. Several immunological parameters were evaluated including ,-interferon (IFN-,), interleukin-2 (IL-2), nitric oxide (NO) and prostaglandin E2 (PGE2). The combined treatment with melatonin and meloxicam significantly enhanced the release of IL-2 and INF-, into animals' serum, when compared with the infected control groups during the course of infection. Furthermore, the blockade of PGE2 synthesis and the increased release of NO by macrophage cells from T. cruzi -infected animals contributed to regulate the production of Th1 subset cytokines significantly reducing the parasitaemia in animals treated with the combination of both substances. Therefore, our results suggest that the association of melatonin and meloxicam was more effective in protecting animals against the harmful actions of T. cruzi infection as compared with the treatments of meloxicam or melatonin alone. [source] Influence of lipopolysaccharide and interleukin-6 on RANKL and OPG expression and release in human periodontal ligament cellsAPMIS, Issue 10 2009ANNA C. KRAJEWSKI Recent research into periodontal disease pathology focuses on the role of receptor activator of nuclear factor-,B ligand (RANKL) and osteoprotegerin (OPG) in periodontal bone destruction processes. RANKL regulates the differentiation of osteoclast by binding to its specific receptor RANK, while OPG inhibits the differentiation of osteoclasts by binding RANKL and therefore preventing RANKL to bind RANK. The aim of the present study was to investigate the influence of Porphyromonas gingivalis lipopolysaccharide (LPS) and interleukin-6 (IL-6) on RANKL and OPG expression and release in periodontal ligament (PDL) cells. Human PDL cells were stimulated for 48 h with purified P. gingivalis LPS and IL-6. OPG and sRANKL release were assessed by using enzyme-linked immunosorbent assay technique. OPG and RANKL expression was quantitatively measured by using the real-time PCR technique. Whereas P. gingivalis LPS induced sRANKL release, expression was only slightly increased, IL-6 did not show an effect on RANKL expression or release. In conclusion the data demonstrate that stimulation of PDL cells with P. gingivalis LPS leads to an increased release of sRANKL, rather than increased RANKL expression. Through this action, P. gingivalis LPS may exert its biological effect on osteoclast formation and bone resorption. [source] Glutamine metabolism: Role in acid-base balance,BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 5 2004Lynn Taylor Abstract The intent of this review is to provide a broad overview of the interorgan metabolism of glutamine and to discuss in more detail its role in acid-base balance. Muscle, adipose tissue, and the lungs are the primary sites of glutamine synthesis and release. During normal acid-base balance, the small intestine and the liver are the major sites of glutamine utilization. The periportal hepatocytes catabolize glutamine and convert ammonium and bicarbonate ions to urea. In contrast, the perivenous hepatocytes are capable of synthesizing glutamine. During metabolic acidosis, the kidney becomes the major site of glutamine extraction and catabolism. This process generates ammonium ions that are excreted in the urine to facilitate the excretion of acids and bicarbonate ions that are transported to the blood to partially compensate the acidosis. The increased renal extraction of glutamine is balanced by an increased release from muscle and liver and by a decreased utilization in the intestine. During chronic acidosis, this adaptation is sustained, in part, by increased renal expression of genes that encode various transport proteins and key enzymes of glutamine metabolism. The increased levels of phosphoenolpyruvate carboxykinase result from increased transcription, while the increase in glutaminase and glutamate dehydrogenase activities result from stabilization of their respective mRNAs. Where feasible, this review draws upon data obtained from studies in humans. Studies conducted in model animals are discussed where available data from humans is either lacking or not firmly established. Because there are quantitative differences in tissue utilization and synthesis of glutamine in different mammals, the review will focus more on common principles than on quantification. [source] Development of the method for evaluating protective effect of food factors on THP-1-induced damage to human intestinal Caco-2 monolayersBIOFACTORS, Issue 1-4 2004Fumiko Watanabe Abstract Immune cells located in the intestinal epithelium interact with intestinal epithelial cells via soluble factors. In this study, a new in vitro model using a coculture system was constructed to analyze the interaction between intestinal epithelial cells and macrophage-like cells. Human intestinal epithelial Caco-2 cells were differentiated on semipermeable membranes. Human monocytic THP-1 cells were differentiated to macrophage-like cells and then cocultured on the basolateral side of the Caco-2 cell monolayers. By coculturing for 48 hours, an increased release of lactate dehydrogenase from the Caco-2 cells and a decrease in the transepithelial electrical resistance of the monolayers were observed, suggesting that the coculture with THP-1 induced some disruption of the Caco-2 cells. This disruption was significantly suppressed by adding the anti-TNF-, antibody to the medium, suggesting that TNF-, secreted from THP-1 caused damage to the Caco-2 cells. It is also suggested that this phenomenon is similar to that observed with inflammatory bowel disease (IBD). The effects of food factors on the cells in this coculture system were examined. The disruption of the Caco-2 cell monolayers was significantly reduced by adding caffeine to the medium on the apical side. It is hoped that this coculture system will be a good model for the treatment of IBD. [source] Human cytomegalovirus induces a direct inhibitory effect on antigen presentation by monocyte-derived immature dendritic cellsBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2002Ulrich Grigoleit Summary. The hypothesis that productive infection of monocyte-derived immature dendritic cells (DCs) by the human cytomegalovirus (HCMV) is associated with decreased immunostimulatory capacity was tested in this study. DCs were infected with 60,80% efficiency by HCMV strain TB40/E. Infected versus uninfected cells were analysed by fluorescence-activated cell sorting and by immunocytochemistry for surface expression of major histocompatibility complex (MHC) and co-stimulatory molecules as well as cytokine secretion during the 3 d after infection. The immunostimulatory capacity of these cells was measured by mixed leucocyte reaction. In spite of the fact that HCMV infection of DCs induced an increased release of tumour necrosis factor-, (TNF-,) and a decreased interleukin 10 (IL-10) production, expression of MHC class I and II, as well as CD40 and CD80 molecules, were downregulated on infected DCs. The mixed leucocyte reaction showed significantly reduced immunostimulatory capacity of infected DC cultures. Simultaneous detection of MHC antigens and virus antigens by double immunofluorescence revealed that downregulation occurred only on infected cells, but not on uninfected bystander cells. These findings demonstrate on a single cell level, together with the marked downregulation of MHC and co-stimulatory molecules in the presence of high TNF-, and low IL-10 levels, a direct inhibitory effect of HCMV on antigen presentation by immature DCs independent of soluble mediators. [source] The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, ,ecstasy') to ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2002Annis O Mechan The pharmacology of the acute hyperthermia that follows 3,4-methylenedioxymethamphetamine (MDMA, ,ecstasy') administration to rats has been investigated. MDMA (12.5 mg kg,1 i.p.) produced acute hyperthermia (measured rectally). The tail skin temperature did not increase, suggesting that MDMA may impair heat dissipation. Pretreatment with the 5-HT1/2 antagonist methysergide (10 mg kg,1), the 5-HT2A antagonist MDL 100,907 (0.1 mg kg,1) or the 5-HT2C antagonist SB 242084 (3 mg kg,1) failed to alter the hyperthermia. The 5-HT2 antagonist ritanserin (1 mg kg,1) was without effect, but MDL 11,939 (5 mg kg,1) blocked the hyperthermia, possibly because of activity at non-serotonergic receptors. The 5-HT uptake inhibitor zimeldine (10 mg kg,1) had no effect on MDMA-induced hyperthermia. The uptake inhibitor fluoxetine (10 mg kg,1) markedly attenuated the MDMA-induced increase in hippocampal extracellular 5-HT, also without altering hyperthermia. The dopamine D2 antagonist remoxipride (10 mg kg,1) did not alter MDMA-induced hyperthermia, but the D1 antagonist SCH 23390 (0.3 , 2.0 mg kg,1) dose-dependently antagonized it. The dopamine uptake inhibitor GBR 12909 (10 mg kg,1) did not alter the hyperthermic response and microdialysis demonstrated that it did not inhibit MDMA-induced striatal dopamine release. These results demonstrate that in vivo MDMA-induced 5-HT release is inhibited by 5-HT uptake inhibitors, but MDMA-induced dopamine release may not be altered by a dopamine uptake inhibitor. It is suggested that MDMA-induced hyperthermia results not from MDMA-induced 5-HT release, but rather from the increased release of dopamine that acts at D1 receptors. This has implications for the clinical treatment of MDMA-induced hyperthermia. British Journal of Pharmacology (2002) 135, 170,180; doi:10.1038/sj.bjp.0704442 [source] Interleukin-6 receptor superantagonist Sant7 inhibits TGF-,-induced proliferation of human lung fibroblastsCELL PROLIFERATION, Issue 3 2008L. Gallelli Therefore, the aim of this study was to investigate in primary cultures of normal and fibrotic human lung fibroblasts (HLF), exposed to either IL-6 or TGF-,1, the effects on phosphorylation of mitogen-activated protein kinases (MAPK) and cell growth of IL-6 signalling inhibition, performed by the IL-6 receptor superantagonist Sant7.Materials and methods:,MAPK phosphorylation was detected by Western blotting, HLF viability and proliferation were evaluated using the trypan blue staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, respectively. Results:,Sant7, at a concentration of 1 µg/mL, was capable of significantly inhibiting HLF proliferation and MAPK phosphorylation induced by cell exposure to IL-6 (100 ng/mL) or TGF-,1 (10 ng/mL), whose actions were more evident in fibrotic cells. Conclusions:,These findings suggest that, in HLFs derived from patients with ILDs, the proliferative mechanisms activated by TGF-,1 are at least in part mediated by an increased release of IL-6, leading to phosphorylation-dependent MAPK activation. Such preliminary findings may thus open new therapeutic perspectives for fibrogenic ILDs, based on inhibition of signal transduction pathways stimulated by the IL-6 receptor. [source] Impaired Heart Function And Noradrenaline Release After Ischaemia In Stroke-Prone Spontaneously Hypertensive RatsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2000Hong Chen SUMMARY 1. Stroke-prone spontaneously hypertensive rats (SHRSP) are a strain of rat that exhibit severely high blood pressure and stroke attacks at an early age, but their heart function in vitro has seldom been studied in detail. Although the activity of the sympathetic nervous system is known to increase after myocardial ischaemia, there is little information about the cardiac release of noradrenaline (NA) associated with heart function after ischaemia in SHRSP. The aim of the present study was to examine heart function and cardiac NA release after ischaemia in SHRSP. 2. Isolated hearts of 4- and 8-month-old SHRSP and age-matched Wistar-Kyoto (WKY) rats were perfused in a working heart preparation and were subjected to 30 min ischaemia followed by 30 min reperfusion. Heart function and coronary flow were monitored throughout the experiment. Coronary effluent was collected for determination of NA using high- performance liquid chromatography coupled with electrochemical detection. 3. Under baseline conditions, cardiac output of 4-month-old SHRSP was slightly but significantly decreased compared with that of WKY rats (P < 0.05), although coronary flow was maintained normally at this age. Eight-month-old SHRSP showed a further impairment of systolic heart function, with lower coronary flow and higher coronary vascular resistance under baseline conditions. Elevated left ventricular end-diastolic pressure was evident in SHRSP at both ages before ischaemia. Heart function was severely damaged after 30 min global ischaemia in SHRSP from both age groups. Stroke-prone spontaneously hypertensive rats also showed lower coronary flow and higher coronary vascular resistance during reperfusion. 4. Coronary NA was not detectable in WKY rats or SHRSP at 4 months of age under baseline conditions. In 8-month-old SHRSP, pre-ischaemic NA release was significantly higher than that in age-matched WKY rat controls. The concentration of NA in the coronary effluent of SHRSP during reperfusion was also significantly higher than that of WKY rats at both ages. 5. These data demonstrate that SHRSP have early impairment of both systolic and diastolic heart function compared with WKY rats. Severe damage of heart function and coronary flow after ischaemia in SHRSP was accompanied with an increased release of NA, which may play a harmful role in heart function impairment in SHRSP after ischaemia. [source] | ||||||||||||||||||||||