Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polarized expression of guanylyl cyclase-coupled natriuretic peptide receptors, types A (GC-A) and B (GC-B), was measured in inner medullary collecting ducts (IMCD) of normal and ischemic rat kidneys, as well as in IMCD cells. Exposure of normal rat kidney medulla to an anti-GC-A antibody demonstrated a propensity of receptor staining on the cellular basal membrane. The polarization of GC-A receptors was lost in the ischemic kidney. The maximal binding capacity of 125I-atrial natriuretic factor (ANF) to the basal membrane of the inner medullary cell line mIMCD-K2 was five times greater than that to the apical membrane. ANF or C-type natriuretic peptide (CNP) added to the basal side of cultured cells resulted in guanosine 3',5'-cyclic monophosphate formation that was greater than when applied to the apical side. Depletion of ATP stores in cultured cells was followed by an increase of 125I-ANF binding to apical cellular membranes. Similar results were obtained when receptor guanylyl cyclase activity was assayed. In conclusion, these results suggest that functional GC-A and GC-B receptors are present predominantly on the basal membrane of IMCD. However, depletion of cellular ATP stores such as in ischemia is followed by a partial loss of polarization.
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PMID:Polarized distribution of renal natriuretic peptide receptors in normal physiology and ischemia. 859 88

Neuronal and glial cell swelling occurs rapidly in ischemia as part of the cytotoxic response. Astrocytic swelling is known to result in large extracellular increases in certain amino acids, including glutamate, aspartate and taurine, as part of the regulatory volume decrease (RVD) response inherent to these and other cells. RVD in astrocytic cultures is inhibited by anion channel blockers. In this study, we compared the effects of three anion channel blockers on the ischemia/reperfusion-evoked release of amino acids from the in vivo rat cerebral cortex. Twenty minutes of four vessel cerebral ischemia caused significant increases in cortical superfusate levels of aspartate, glutamate, GABA, taurine and phosphoethanolamine. During reperfusion there were delayed increases in the level of glycine, alanine and serine. Glutamine levels were not affected. Cl- channel blockers, 4-acetamido-4'-isothiocyanostrilbene-2,2'-disulfonic acid (SITS, 2 mM), 5-nitro-2-(3-phenyl-propylamino)benzoic acid (NPPB, 350 microM) and dipyridamole (200 microM) depressed basal releases of glutamate and taurine and the ischemia/reperfusion-evoked releases of aspartate, glutamate, taurine and phosphoethanolamine. The results suggest that diffusion of amino acids through an anion channel may be partially responsible for the elevated extracellular levels of excitotoxic and other amino acids that occur during cerebral ischemia/reperfusion.
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PMID:Inhibition by anion channel blockers of ischemia-evoked release of excitotoxic and other amino acids from rat cerebral cortex. 920 27

-Previous studies suggested that atrial natriuretic peptide gene (Anp) and brain natriuretic peptide gene (Bnp) are plausible candidate genes for susceptibility to stroke and for sensitivity to brain ischemia in the stroke-prone spontaneously hypertensive rat (SHRSP). We performed structural and functional analyses of these 2 genes in SHRSP from Glasgow colonies (SHRSPGla) and Wistar-Kyoto rats from Glasgow colonies (WKYGla) and developed a radiation hybrid map of the relevant region of rat chromosome 5. Sequencing of the coding regions of the Anp and Bnp genes revealed no difference between the 2 strains. Expression studies in brain tissue showed no differences at baseline and at 24 hours after middle cerebral artery occlusion. Plasma concentrations of atrial natriuretic peptide (ANP) did not differ between the SHRSPGla and WKYGla, whereas concentrations of brain natriuretic peptide were significantly higher in the SHRSPGla as compared with the WKYGla (n=11 to 14; 163+/-21 pg/mL and 78+/-14 pg/mL; 95% confidence interval 31 to 138, P=0.003). We did not detect any attenuation of endothelium-dependent relaxations to bradykinin or ANP in middle cerebral arteries from the SHRSPGla; indeed the sensitivity to ANP was significantly increased in arteries harvested from this strain (WKYGla: n=8; pD2=7. 3+/-0.2 and SHRSPGla: n=8; pD2=8.2+/-0.15; P<0.01). Moreover, radiation hybrid mapping and fluorescence in situ hybridization allowed us to map the Anf marker in the telomeric position of rat chromosome 5 in close proximity to D5Rat48, D5Rat47, D5Mgh15, and D5Mgh16. These results exclude Anp and Bnp as candidate genes for the sensitivity to brain ischemia and pave the way to further congenic and physical mapping strategies.
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PMID:Genes encoding atrial and brain natriuretic peptides as candidates for sensitivity to brain ischemia in stroke-prone hypertensive rats. 993 Nov 19

The objective of this study was to examine the role of chloride (Cl-) channels in the myocardial protection of ischemic preconditioning (IP). Isolated rabbit ventricular myocytes were preconditioned with 10-minute simulated ischemia (SI) and 20-minute simulated reperfusion (SR) or not preconditioned (control). The myocytes then received 180-minute SI or 45-minute SI/120-minute SR. Indanyloxyacetic acid 94 (IAA-94, 10 micromol/L) or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 1 micromol/L) was administered before IP or before SI or SI/SR to inhibit Cl- channels. Electrophysiological studies indicate that these drugs, at the concentrations used, selectively abolished Cl- currents activated under hypo-osmotic conditions (215 versus 290 mOsm). IP significantly (P<0.001) reduced the percentage of dead myocytes after 60-minute (30.8+/-1.3%, mean+/-SEM), 90-minute (35.3+/-1.3%), and 120-minute (39.2+/-1.7%) SI compared with controls (44.7+/-1.6%, 54.5+/-1.3%, and 58.9+/-1.8%, respectively) and after 45-minute SI/120-minute SR (36.3+/-0.6%) compared with control (56.6+/-2.2%). Hypo-osmotic stress also produced protection similar to IP. IAA-94 or NPPB abolished the protection of both IP and hypo-osmotic stress. In buffer-perfused rabbit hearts preconditioned with three 5-minute ischemia/10-minute reperfusion cycles given before the 40-minute long ischemia and 60-minute reperfusion, IP significantly (P<0.0001) reduced infarct size (IP+vehicle, 4.7+/-0.9%, versus control+vehicle, 26.6+/-3.3%; mean+/-SEM). Again, IAA-94 or NPPB abolished the protection of IP. Our results implicate Cl- channels in the IP protection of the myocardium against ischemic/reperfusion injury and demonstrate that hypo-osmotic stress is capable of preconditioning cardiomyocytes.
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PMID:Chloride channel inhibition blocks the protection of ischemic preconditioning and hypo-osmotic stress in rabbit ventricular myocardium. 1173 94

Plasma atrial natriuretic peptide (ANP) concentration increases during ventricular arrhythmias and rapid ventricular pacing but less is known about plasma brain natriuretic peptide (BNP) and endothelin (ET-1). In the present study concentrations of ANP, the amino terminal part of the proANP (NT-proANP), BNP, and ET-1 were measured in the coronary sinus and femoral artery before and at the end of rapid ventricular pacing in 15 patients with coronary arterial disease. The changes were compared with the changes in mean arterial blood pressure, pulmonary capillary wedge pressure (PCWP), transcardiac differences in pH, pCO2, lactate, and norepinephrine. There was an increase in PCWP and a transient decrease in blood pressure after initiation of pacing. Pacing caused a decrease in ST-segment, transcardiac difference of norepinephrine, lactate extraction, pCO2 difference, and an increase in pH difference. Concentration of ANP in the coronary sinus and femoral artery and its transcardiac difference increased during pacing (P < 0.001), whereas changes in NT-proANP were small and BNP and ET-1 levels remained unchanged. The change in transcardiac ANP difference correlated with the change in lactate (r = 0.53, P < 0.05) but not that of norepinephrine, PCWP, or blood pressure. The results show that the plasma concentration of ANP increases more than that of NT-proANP during rapid ventricular pacing. Ischemia-induced release of ANP and its diminished elimination may contribute to the increased plasma ANP level.
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PMID:Vasoactive peptide release in relation to hemodynamic and metabolic changes during rapid ventricular pacing. 1045 35

Volume-regulated chloride channels have recently been proposed to be end-effectors in ischemic preconditioning. The present study attempted to confirm this hypothesis by looking both at cardioprotection and channel activity. In isolated rabbit cardiomyocytes, hypo-osmotic stress (167 mosm/l) induced a current with a magnitude of 2-5 pA/pF at 60 mV. That current could be blocked by the selective chloride channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) or indanyloxyacetic acid 94 (IAA-94), but only at 100 microM and 1 m M respectively. Lower concentrations were not effective. Because the channel-blocking concentrations were toxic in isolated perfused rabbit hearts, as evidenced by cessation of cardiac contraction and massive infarction, neither agent could be tested against preconditioning's anti-infarct effect. NPPB and IAA-94 at 1 microM and 10 microM, respectively (the doses used in a previous report), did not affect coronary flow, heart rate and developed pressure, and also did not prevent the infarct size reduction of ischemic preconditioning with 5 min global ischemia/10 min reperfusion preceding 30 min of regional ischemia and 120 min of reperfusion [11. 4(+/-3.6) and (11.1(+/-3.7)% infarction of risk area, respectively]. The volume-regulated chloride and organic osmolyte channel blocker 4, 4;-diisothiocyanostilbene-2,2;-disulfonic acid (DIDS) at 100 microM blocked the hypo-osmotically induced current in myocytes, but again could not be used, since it induced total cessation of cardiac contraction and reduced infarct size in non-preconditioned hearts. Our data do not confirm a prior study on a causal role for volume-regulated chloride channels in the protection of ischemic preconditioning. This hypothesis remains to be adequately tested.
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PMID:No confirmation for a causal role of volume-regulated chloride channels in ischemic preconditioning in rabbits. 1160 30

A quantitative trait locus on chromosome 5 in the rat is linked to sensitivity to brain ischemia in the stroke-prone spontaneously hypertensive rat (SHRSP). The genes encoding atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) that map to this location have been excluded as candidate genes. We examined dishevelled-1 (DVL-1) as a further candidate gene. DVL-1 had not yet been identified in the rat, but Anp, Bnp, and DVL-1 map to the homologous regions of the rat chromosome 5 quantitative trait locus in both mice and man. Furthermore, DVL-1 is involved in the Notch signalling system, which plays a role in the disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the symptoms of, which include ischaemic stroke. We show with radiation hybrid mapping that rat DVL-1 indeed maps to chromosome 5, where it is positioned immediately next to microsatellite marker D5Rat49. We sequenced the complete coding sequence and a large part of the intronic genomic sequence for the SHRSP strain and its reference Wistar-Kyoto strain. The DVL-1 sequence in the two strains was identical. Our results essentially exclude the DVL-1 gene as the cause for sensitivity to cerebral ischaemic insult in this rat model of stroke.
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PMID:Mapping and sequencing rat dishevelled-1: a candidate gene for cerebral ischaemic insult in a rat model of stroke. 1135 32

Acute myocardial infarction (AMI) remains the leading cause of death in developed countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury. Endothelial P-selectin-mediated infiltration of neutrophils plays a key role in reperfusion injury. However, the mechanism of the P-selectin induction is not known. Here we show that infarct size after ischemia/reperfusion was significantly smaller in mice lacking guanylyl cyclase-A (GC-A), a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration in coronary endothelial P-selectin expression. Pretreatment with HS-142-1, a GC-A antagonist, also decreased infarct size and P-selectin induction in wild-type mice. In cultured endothelial cells, activation of GC-A augmented H2O2-induced P-selectin expression. Furthermore, ischemia/reperfusion-induced activation of NF-kappaB, a transcription factor that is known to promote P-selectin expression, is suppressed in GC-A-deficient mice. These results suggest that inhibition of GC-A alleviates ischemia/reperfusion injury through suppression of NF-kappaB-mediated P-selectin induction. This novel, GC-A-mediated mechanism of ischemia/reperfusion injury may provide the basis for applying GC-A blockade in the clinical treatment of reperfusion injury.
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PMID:Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-kappaB activation and alleviates myocardial ischemia/reperfusion injury. 1145 73

Kupffer cells (KCs), the resident macrophages of the liver, contribute prominently to liver injury by inflammatory mediators. Pre-conditioning with the atrial natriuretic peptide (ANP), known also as a regulator of macrophage functions, attenuates hepatic ischemia-reperfusion injury. Therefore, the aim of this study was to determine the presence of functional ANP receptors on isolated KCs and to investigate whether this hepatoprotective hormone influences the activation of KCs. KCs were isolated by collagenase/pronase digestion followed by elutrial centrifugation and cultured for 1 to 3 days. Intracellular cyclic guanosine 3'5'-monophosphate (cGMP) concentrations were measured by radioimmunoassay after treating the cells with sodium nitroprusside or ANP. KCs were stimulated with bacterial lipopolysaccharide in the presence or absence of ANP, and inflammatory mediators were determined. Phagocytosis was assayed using Coumarin-labeled latex particles and flow cytometric analysis. Treatment of KCs with ANP but not with sodium nitroprusside resulted in a significant elevation of intracellular cGMP levels indicating functional type A natriuretic peptide receptors (NPR-As). ANP significantly reduced lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNFalpha) secretion, paralleled by an increased cell-associated TNFalpha. LPS-induced TNFalpha mRNA expression was not affected. ANP significantly increased phagocytotic activity of KCs via NPR-A. No effect of ANP on LPS-activated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein levels, iNOS mRNA expression, nitric oxide, and PGE2-production was observed. We demonstrated functional cGMP-dependent ANP receptors in isolated rat KCs. ANP reduced TNFalpha release possibly by influencing post-translational processing of TNFalpha in LPS-activated KCs. In addition, we demonstrated that ANP enhances phagocytosis in KCs. These effects may contribute to the hepatoprotective actions of ANP.
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PMID:The atrial natriuretic peptide as a regulator of Kupffer cell functions. 1202 55

To maintain the good quality of life in elderly, it is important to diagnose and asymptomatic advanced or prone to rupture atherosclerosis by using non-invasive techniques and it is also important to treat and prevent the progression of atherosclerotic disease. Comprehensive geriatric assessment is useful for maintain the good quality of life as well as evaluation of activity of daily life. Treadmill exercise test which protocol was arranged for Japanese elderly revealed high incidences of coronary ischemia susceptible patients in elderly diabetic patients. Concomitant measurement of blood pressure of lower extremities is also useful for early diagnosis of arteriosclerosis obliterence. Vascular endocrinological examination such as brain natriuretic peptide is expectable for early diagnosis of latent impairment of cardiac function. Evaluation of endothelial function by measuring flow mediated dilatation and evaluation of narrowing carotid artery by using ultrasound echocardiograph is useful. These examinations are expectable for future treatment of elderly patients.
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PMID:[Quality of life in elderly with atherosclerotic diseases]. 1218 4


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