neuropeptide-y and Reperfusion-Injury

Netrin-1 has been found to protect kidneys from ischemia/reperfusion injury. In this study, we aimed to address whether the protective effects were mediated through suppression of oxidative stress and neuropeptide Y. Compared to sham-operated animals, animals after ischemia/reperfusion showed marked kidney damage and significantly increased levels of serum creatinine, blood urea nitrogen, malondialdehyde, and neuropeptide Y. Renal myeloperoxidase activity was elevated in animals with ischemia/reperfusion relative to sham-operated animals, whereas renal superoxide dismutase activity was reduced. Netrin-1 pretreatment attenuated ischemia/reperfusion-induced functional and pathological changes in the kidney. Moreover, the ischemia/reperfusion-induced changes in the oxidative stress biomarkers and neuropeptide Y were significantly counteracted by prior administration of netrin-1. Taken together, our data showed that netrin-1 pretreatment prevented renal ischemia/reperfusion injury, at least partially through reduction of oxidative stress and neuropeptide Y expression.

Topics: Animals; Blood Urea Nitrogen; Creatinine; Humans; Immunohistochemistry; Kidney; Kidney Function Tests; Male; Nerve Growth Factors; Netrin-1; Neuropeptide Y; Oxidative Stress; Protective Agents; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Suppressor Proteins

Cardiac function is regulated by a balance of sympathetic and parasympathetic transmission. Neuropeptide Y (NPY) and galanin (GAL) released from cardiac sympathetic neurons inhibits parasympathetic transmission in the heart. Sympathetic peptides may contribute to autonomic imbalance, which is characterized by increased sympathetic and decreased parasympathetic transmission and contributes to life threatening cardiovascular pathologies. Several gp130 cytokines are increased in the heart after myocardial infarction (MI), and these cytokines stimulate neuropeptide expression in sympathetic neurons. We used mice whose sympathetic neurons lack the gp130 receptor (gp130(DBH-Cre/lox) mice) to ask if cytokine activation of gp130 regulated neuropeptide expression in cardiac sympathetic nerves after MI. Myocardial infarction decreased NPY mRNA through a gp130 independent mechanism and increased VIP and PACAP mRNA via gp130, while GAL mRNA was unchanged. Immunohistochemistry revealed a gp130-dependent increase in PACAP38 in cells of the stellate ganglion after MI, and PACAP was detected in pre-ganglionic fibers of all genotypes and surgical groups. VIP was identified in a few sympathetic nerve fibers in all genotypes and surgical groups. GAL and PACAP38 were not detected in sham hearts, but peptide immunoreactivity was high in the infarct three days after MI. Surprisingly, peptides were abundant in cells that co-labeled with macrophage markers F4/80 and MAC2, but were not detected in sympathetic axons. PACAP protects cardiac myocytes from apoptosis, and GAL stimulates axon regeneration in addition to inhibiting parasympathetic transmission. Thus, these peptides may play an important role in cardiac and neuronal remodeling after ischemia-reperfusion.

Topics: Animals; Cytokine Receptor gp130; Galanin; Heart; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Ischemia; Myocardium; Neuropeptide Y; Neuropeptides; Pituitary Adenylate Cyclase-Activating Polypeptide; Reperfusion Injury; Sympathetic Nervous System; Vasoactive Intestinal Peptide

The aim of the present study was to reveal the effect of liver ischemia–reperfusion injury (LIRI) on the activity of selected neuronal phenotypes in rat brain by applying dual Fos-oxytocin (OXY), vasopressin (AVP), tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), corticoliberine (CRH), and neuropeptide Y (NPY) immunohistochemistry. Two liver ischemia–reperfusion models were investigated: (i) single ligation of the hepatic artery (LIRIa) for 30 min and (ii) combined ligation of the portal triad (the common hepatic artery, portal vein, and common bile duct) (LIRIb) for 15 min. The animals were killed 90 min, 5 h, and 24 h after reperfusion. Intact and sham operated rats served as controls. As indicated by semiquantitative estimation, increases in the number of Fos-positive cells mainly occurred 90 min after both liver reperfusion injuries, including activation of AVP and OXY perikarya in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, and TH, NPY, and PNMT perikarya in the catecholaminergic ventrolateral medullar A1/C1 area. Moreover, only PNMT perikarya located in the A1/C1 cell group exhibited increased Fos expression 5 h after LIRIb reperfusion. No or very low Fos expression was found 24 h after reperfusion in neuronal phenotypes studied. Our results show that both models of the LIRI activate, almost by the same effectiveness, a number of different neuronal phenotypes which stimulation may be associated with a complex of physiological responses induced by (1) surgery (NPY, TH, PNMT), (2) hemodynamic changes (AVP, OXY, TH, PNMT), (3) inflammation evoked by ischemia and subsequent reperfusion (TH), and (4) glucoprivation induced by fasting (NPY, PNMT, TH). All these events may contribute by different strength to the development of pathological alterations occurring during the liver ischemia–reperfusion injury.

Topics: Animals; Brain; Corticotropin-Releasing Hormone; Immunohistochemistry; Liver; Male; Neurons; Neuropeptide Y; Oxytocin; Phenotype; Phenylethanolamine N-Methyltransferase; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Reperfusion Injury; Tyrosine 3-Monooxygenase; Vasopressins

An intracerebroventricular (i.c.v.) injection of neuropeptide Y (NPY) or [Leu31, Pro34]-NPY (non-Y2 receptor agonist) given during middle cerebral artery occlusion (MCAO) increases the infarct volume and nitric oxide (NO) overproduction in the rat brain. An i.c.v. injection of NPY3-36 (non-Y1 receptor agonist) has no effects, while BIBP3226 (selective Y1 receptor antagonist) reduces the infarct volume and NO overproduction. This study examined the effects of NPY or its receptor analog on the immunoreactivity (ir) for three isoforms of NO synthase (NOS) following 1 h of MCAO and 3 h of reperfusion. Focal ischemia/reperfusion led to increased ir for neuronal NOS (nNOS) within the ipsilateral caudate putamen and insular cortex. NPY or [Leu31, Pro34]-NPY enhanced but BIBP3226 suppressed such increase in the nNOS-ir. Focal ischemia/reperfusion also led to an ipsilateral increase in extent and/or intensity of the ir for endothelial NOS (eNOS) in the caudate putamen and/or parietal cortex. NPY or [Leu31, Pro34]-NPY suppressed but BIBP3226 enhanced such change in the eNOS-ir. NPY3-36 did not consistently influence the nNOS-ir or eNOS-ir following MCAO. Specific ir for inducible NOS was undetectable. These opposing effects of NPY-Y1 receptor activation or inhibition on nNOS and eNOS may lead to harmful or beneficial consequences following ischemia/reperfusion.

Topics: Animals; Anti-Anxiety Agents; Arginine; Brain; Brain Ischemia; Cerebral Arteries; Immunohistochemistry; Male; Neurons; Neuropeptide Y; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Protein Isoforms; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y; Reperfusion Injury; Temperature; Time Factors

To observe the effects of Salvia miltiorrhiza (SM) on levels of neuropeptide Y1-36 and calcitonin gene-related peptide immune reactive substances (ir-NPY, ir-CGRP) in blood plasma and pons-oblongata after hypoxia-ischemic brain injury (HIBI) in neonatal rats.. Seven-day old rats were randomized into HIBI group (A), HIBI + SM group (B) and sham operation group(C). And each group was subdivided into 4 subgroups according to the different time after operation. 0.5 ml SM was injected intraperitoneally immediately and every 12 hrs afterwards. Changes of ir-NPY and ir-CGRP levels in plasma and pons-oblongata were observed immediately and 12, 24 and 48 hrs after HIBI by radioimmunoassay.. Plasma levels of ir-NPY and ir-CGRP in different times after HIBI were all significantly raised but those in pons-oblongata were either raised or lowered to a certain degree. Part of the elevated ir-NPY could be reversed by SM injection.. Central and peripheral neuropeptide Y1-36 and calcitonin gene-related peptide take part in the pathophysiological process of HIBI, SM could partially reverse the abnormal post-HIBI elevation of ir-NPY, which may be one of the pathways of SM in promoting recovery of damaged brain function.

Topics: Animals; Animals, Newborn; Brain Ischemia; Calcitonin Gene-Related Peptide; Drugs, Chinese Herbal; Female; Male; Neuropeptide Y; Peptide Fragments; Phytotherapy; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Salvia miltiorrhiza

To observe the changes of some neuropeptides and the effect of Fusheng powder (FSP) on neuropeptides in rat's brains in a stable cerebral ischemia and reperfusion (I/L) model.. The models of rat's brain injured were established by repeated cerebral I/R in rats with hyperlipidemia. Radioimmunoassay (RIA) was performed to determine the level of neuropeptides.. After 1 day of I/R, compared with the control group, the contents of endothelin-1 (ET-1), calcitonin gene related peptide (CGRP) and neuropeptide Y (NPY) in the model animals were significantly increased by 24.3%, 33.7% and 51.86% respectively, while the level of somatostatin (SS) decreased by 37.86% (all P < 0.01). Meanwhile after FSP treatment, the contents of neuropeptides were alleviated respectively (P < 0.05, P < 0.01). Apart from the ET, the releases of CGRP, NPY and SS were all recovered in different degree after 7 days of I/R.. There were obvious imbalance of neuropeptides in rat's brains after cerebral I/R and the FSP might antagonize ischemic injury of brain through modulating neuropeptides, which may be one of the therapeutical mechanism in treating cerebral vascular diseases with FSP.

Topics: Animals; Brain; Brain Ischemia; Calcitonin Gene-Related Peptide; Drugs, Chinese Herbal; Endothelin-1; Hyperlipidemias; Male; Neuropeptide Y; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury

We have investigated the effects of ischaemia on neuropeptide Y (NPY) mechanisms involved in sympathetic vascular control of the pig kidney in vivo. Reperfusion after 2 h of renal ischaemia was associated with local overflow of noradrenaline (NA) but not of NPY-like immunoreactivity (-LI). Renal sympathetic nerve stimulation 10 min into reperfusion evoked markedly reduced vasoconstrictor effects and significantly less overflow of NA (reduced by 70% from the pre-ischaemic conditions), whereas NPY-LI overflow was unaltered. Renal vasoconstrictor responses to exogenous peptide YY (PYY), phenylephrine and angiotensin II were strongly attenuated after this ischaemic period, while vasoconstriction to alpha, beta-methylene ATP was maintained to a larger extent. The renal vascular responses and NA overflow had become partially normalized within a 2 h recovery period. In contrast, the renal vasoconstrictor response and the overflow of NPY-LI upon sympathetic nerve stimulation were enhanced after 15 min of renal ischaemia. In parallel, the PYY-evoked renal vasoconstriction was selectively and markedly prolonged after the 15 min of ischaemia. In the presence of the NPYY1 receptor antagonist BIBP 3226, the augmented vascular response to nerve stimulation was significantly attenuated. We conclude that reperfusion after 2 h of renal ischaemia is associated with local overflow of NA, whereas the sympathetic nerve-evoked release of NA and the reactivity of the renal vasculature to vasoconstrictor stimuli are reversibly reduced. Furthermore, possibly due to an impaired local degradation, the role of neurogenically released NPY in renal sympathetic vasoconstriction is enhanced after short-term (15 min) ischaemia compared with control conditions.

Topics: Adrenergic alpha-Agonists; Animals; Arginine; Electric Stimulation; Female; Ischemia; Male; Neuropeptide Y; Norepinephrine; Peptide YY; Phenylephrine; Receptors, Neuropeptide Y; Renal Circulation; Reperfusion Injury; Swine; Sympathetic Nervous System; Time Factors; Vasoconstriction

To investigate whether differences in vulnerability to free radicals might underlie differences among striatal neurons in their vulnerability to neurodegenerative processes such as occur in ischemia and Huntington's disease, we have analyzed the localization of superoxide free radical scavengers in different striatal neuron types in normal rhesus monkey. Single- and double-label immunohistochemical experiments were carried out using antibodies against the enzymes copper, zinc superoxide dismutase (SOD1), or manganese superoxide dismutase (SOD2), and against markers of various striatal cell types. Our results indicate that the striatal cholinergic and parvalbumin interneurons are enriched in SOD1 and/or SOD2, whereas striatal projection neurons and neuropeptide Y/somatostatin (NPY+/SS+) interneurons express only low levels of both SOD1 and SOD2. We also found that projection neurons of the matrix compartment express significantly higher levels of SOD than those in the striosome compartment. Since projection neurons have been reported to be more vulnerable than interneurons and striosome neurons more vulnerable than matrix neurons to neurodegenerative processes, our results are consistent with the notion that superoxide free radicals are at least partly involved in producing the differential neuron loss observed in the striatum following global brain ischemia or in Huntington's disease.

Topics: Animals; Antibodies; Brain Ischemia; Corpus Striatum; Female; Free Radical Scavengers; Humans; Huntington Disease; Immunohistochemistry; Interneurons; Isoenzymes; Macaca mulatta; Male; Nerve Degeneration; Neurons; Neuropeptide Y; Reperfusion Injury; Somatostatin; Superoxide Dismutase

Infrarenal aortic cross-clamping is associated with remote vascular events, including myocardial infarction and renal insufficiency. The purpose of this study was to determine whether hindlimb ischaemia and reperfusion associated with infrarenal aortic cross-clamping results in the production of vasoactive regulatory neuropeptides. A canine model of infrarenal aortic cross-clamping was used for the study. Serial blood samples were drawn, prior to, at the time of, and serially following placement of the clamp and subsequent release of the clamp and reperfusion. Ischaemia resulted in increased mean(s.e.m.) plasma levels of neuropeptide Y (NPY) (initial 10.0(1.8) pmol/l versus ischaemia 24.7(2.3) pmol/l, P < 0.001) and vasoactive intestinal polypeptide (VIP) (initial 2.53(0.5) pmol/l versus ischaemia, 7.3(1.3) pmol/l, P < 0.05). Reperfusion produced three-fold elevation of VIP (initial 2.5(0.5) pmol/l versus reperfusion 9.6(1.5) pmol/l, P < 0.001), two-fold elevation in the plasma levels of endothelin-1 (initial 1.3(0.1) pmol/l versus reperfusion maximum 2.5(0.3) pmol/l, P < 0.01) and NPY (initial 10.0(0.8) pmol/l versus reperfusion maximum 23.9(2.3) pmol/l, P < 0.001). Ischaemia and reperfusion did not alter calcitonin gene-related peptide (CGRP) (a potent vasodilator) levels. Endothelin-1 (ET-1) plasma levels were also increased following haemorrhagic shock (initial 1.3(0.1) pmol/l versus exsanguination 3.4(0.4) pmol/l, P < 0.001), but not during ischaemia (initial 1.3(0.1) pmol/l versus ischaemia maximum 1.7(0.2) pmol/l, P = 0.7). It was concluded that vasoactive regulatory peptides are released following ischaemia, reperfusion and shock in the canine infrarenal aortic revascularization model and, therefore could contribute to remote vascular events observed with infrarenal aortic cross-clamping.

Topics: Animals; Aorta, Abdominal; Calcitonin Gene-Related Peptide; Dogs; Endothelin-1; Female; Ischemia; Leg; Male; Neuropeptide Y; Radioimmunoassay; Reference Values; Reperfusion Injury; Vasoactive Intestinal Peptide