atrial-natriuretic-factor and Brain-Ischemia

This meta-analysis was performed to evaluate the correlations between atrial natriuretic peptide (ANP) genetic polymorphism and its serum ANP levels with the risk of ischemic stroke.. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1st, 2013 without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) or standardized mean difference (SMD) with their 95% confidence interval (95% CI) were calculated. Twelve case-control studies that met all inclusion criteria were included in this meta-analysis. A total of 1285 patients with ischemic stroke and 1088 healthy control subjects were involved in this meta-analysis. Three common single-nucleotide polymorphisms (1837 G/A, 2238 T/C, and 664 G/A) in the ANP gene were assessed.. Our meta-analysis results revealed that ANP 2238 T/C polymorphism might increase the risk of ischemic stroke (C allele vs. T allele: OR=2.26, 95% CI: 1.59-3.23, p<0.001; TC+CC vs. TT: OR=2.26, 95% CI: 1.34-3.81, p=0.002; respectively). However, we found no correlations of ANP 1837 G/A and 664 G/A polymorphisms with ischemic stroke risk (all p>0.05). Furthermore, ischemic stroke patients had higher levels of serum ANP than those of healthy control subjects (SMD=3.12, 95% CI: 1.16-5.07, p=0.002). Our study revealed no publication bias in this meta-analysis (all p>0.05).. Our findings indicate that ANP genetic polymorphism and serum ANP levels may contribute to the development of ischemic stroke. Thus, the ANP genetic polymorphism and serum ANP levels could be potential biomarkers for early detection of ischemic stroke.

Topics: Atrial Natriuretic Factor; Biomarkers; Brain Ischemia; Case-Control Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Stroke

N-terminal pro-brain natriuretic peptide (NT-proBNP) has been shown to be associated with the prognosis of cardiovascular diseases and NT-proBNP level is elevated in patients with acute ischemic stroke. However, the association between NT-proBNP and poor prognosis after ischemic stroke is still uncertain. The aim of this study was to examine whether serum NT-proBNP is associated with global clinical outcomes in a large cohort of patients with acute ischemic stroke.. Baseline serum NT-proBNP level was measured in a subset of 3126 patients with acute ischemic stroke, and the patients were followed up to assess their clinical outcomes within 1year after the stroke. Cox proportional hazard models and logistic regression models were used to assess the effects of NT-proBNP on the primary outcome (composite outcome of death and vascular events) and poor functional outcomes.. This study showed that high NT-proBNP levels increased the risk of a composite outcome of death and vascular events and poor functional outcomes at 1year after stroke onset among ischemic stroke patients with elevated blood pressure, suggesting that NT-proBNP might be a potential prognostic factor for ischemic stroke.

Topics: Atrial Natriuretic Factor; Biomarkers; Brain Ischemia; Female; Follow-Up Studies; Humans; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Protein Precursors; Stroke; Treatment Outcome

The purpose of this study was to examine the prognostic value of midregional pro-atrial natriuretic peptide (MR-proANP) in patients with acute ischemic stroke.. The rapid and reliable estimation of prognosis in acute ischemic stroke is pivotal to optimize clinical care. MR-proANP, a recently described, stable fragment of the ANP precursor hormone, may be useful in this setting.. In a prospective observational study, we measured MR-proANP on admission in plasma of 362 consecutive patients presenting with acute ischemic stroke. The prognostic value of MR-proANP to predict mortality within 90 days and functional outcome (defined as a modified Rankin Scale of ≤2 or ≥3) was evaluated and compared with the National Institutes of Health Stroke Scale (NIHSS) score.. The discriminatory accuracy, calculated with the area under the curve (AUC) of the receiver operating characteristics curve, of MR-proANP to predict death was comparable to the NIHSS (AUC: 0.86 [95% confidence interval (CI): 0.82 to 0.90] and 0.85 [95% CI: 0.81 to 0.89; p = 0.7]). Combined, the accuracy significantly improved (0.92 [95% CI: 0.88 to 0.96; p < 0.01]). The AUC of MR-proANP to predict functional outcome was 0.70 (95% CI: 0.65 to 0.75), similar to the NIHSS (0.75 [95% CI: 0.70 to 0.80]; p = 0.16). The prognostic value of MR-proANP for both outcomes was independent of the NIHSS. Higher MR-proANP concentrations were found in stroke of cardioembolic etiology.. MR-proANP is a prognostic marker in the acute phase of stroke, improving the discriminatory value of the NIHSS, independently predicting post-stroke mortality and functional outcome. (The "COSMOS"-Study [Copeptin in Osmoregulation and Stress Assessment]; NCT00390962).

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Brain Ischemia; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Predictive Value of Tests; Prognosis; Prospective Studies; Stroke

The plasma levels of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) have been measured in 37 patients with acute ischemic stroke, on admission and 3 and 7 days thereafter. The plasma ET-1 levels at the onset of symptoms were about two-fold those observed in age-matched normal volunteers (3.5 +/- 2.26 v 1.54 +/- 0.9 pg/mL, respectively; P < .001). These levels remained significantly elevated during the 7-day study period. The neurologic deficit was assessed daily by Mathew's modified scale (MS). A significant correlation was found between neurologic status on admission and ET-1 plasma values; patients with worse neurologic status (MS < 45 points) had higher ET-1 plasma values than those with better neurologic status (MS > 45 points) (5.4 +/- 2.34 v 3.05 +/- 2.04 pg/mL, respectively, P < .05). The plasma ET-1 values did not correlate either with the site of the infarction or with its primary cause (cardioembolic, lacunar, or atherothrombotic). No significant differences were seen in plasma ET-1 concentrations between patients who eventually died and those who survived the acute event. The plasma ANP were about 18-fold higher in ischemic stroke patients on admission than in controls at admission (110.9 +/- 29.5 v 5.84 +/- 3.96 pg/mL, respectively, P < .01). These values remained significantly elevated on days 3 and 7. There was no correlation between the ANP plasma values and the neurologic status, the site or mechanism of the stroke, or the plasma ET-1 levels. In conclusion, ischemic stroke is associated with marked acute and long-duration increases of ET-1 and ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Brain Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Endothelins; Female; Humans; Male; Middle Aged; Neurologic Examination

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Brain Ischemia; Disease-Free Survival; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Growth Differentiation Factor 15; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Neurofilament Proteins; Peptide Fragments; Predictive Value of Tests; Prospective Studies; S100 Proteins; Stroke; Survival Rate; Tomography, X-Ray Computed

To validate midregional proatrial natriuretic peptide (MR-proANP) for outcome prediction and diagnosis of cardioembolic stroke etiology compared to established clinical variables.. In this prospective multicenter cohort study, we quantified MR-proANP levels in ischemic stroke patients within 24 hours of onset. Primary outcome measures were 90-day mortality, unfavorable functional outcome (modified Rankin Scale score >2), and cardioembolic stroke etiology diagnosed during hospitalization.. MR-proANP is a newly validated blood biomarker providing additional prognostic information for mortality after stroke. Higher MR-proANP levels were associated with cardioembolic stroke etiology and, even more strongly, atrial fibrillation.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Brain Ischemia; Cohort Studies; Disability Evaluation; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Predictive Value of Tests; ROC Curve; Stroke; Treatment Outcome

Functional imaging studies have argued that interactions between cortical motor areas and the cerebellum are relevant for motor output and recovery processes after stroke. However, the impact of the underlying structural connections is poorly understood. To investigate this, diffusion-weighted brain imaging was conducted in 26 well-characterized chronic stroke patients (aged 63 ± 1.9 years, 18 males) with supratentorial ischemic lesions and 26 healthy participants. Probabilistic tractography was used to reconstruct reciprocal cortico-cerebellar tracts and to relate their microstructural integrity to residual motor functioning applying linear regression modeling. The main finding was a significant association between cortico-cerebellar structural connectivity and residual motor function, independent from the level of damage to the cortico-spinal tract. Specifically, white matter integrity of the cerebellar outflow tract, the dentato-thalamo-cortical tract, was positively related to both general motor output and fine motor skills. Additionally, the integrity of the descending cortico-ponto-cerebellar tract contributed to rather fine motor skills. A comparable structure-function relationship was not evident in the controls. The present study provides first tract-related structural data demonstrating a critical importance of distinct cortico-cerebellar connections for motor output after stroke.

Topics: Aged; Atrial Natriuretic Factor; Brain Ischemia; Cerebellum; Cerebral Cortex; Chronic Disease; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Female; Humans; Linear Models; Male; Middle Aged; Motor Activity; Neural Pathways; Stroke; White Matter

The impact of atrial natriuretic peptide (ANP) value for predicting paroxysmal atrial fibrillation (pAF) in ischemic stroke patients remains uncertain.. The consecutive 222 ischemic stroke patients (median 77 [IQR 68-83] years old, 93 females) within 48 hours after onset were retrospectively studied. Plasma ANP and brain natriuretic peptide (BNP) levels were simultaneously measured at admission. Of all, 158 patients had no evidence of atrial fibrillation (AF) (sinus rhythm [SR] group), 25 patients had pAF (pAF group), and the other 39 patients had chronic AF (cAF group). We investigated predicting factors for pAF, with focus on ANP, BNP, and ANP/BNP ratio.. ANP value was significantly higher in the pAF than in the SR group (97 [50-157] mg/dL versus 42 [26-72] mg/dL, P < .05) and further increased in the cAF group (228 [120-392], P < .05 versus pAF and SR groups). Similarly, the BNP value was higher in the pAF than in the SR group (116 [70-238] mg/dL versus 34 [14-72] mg/dL, P < .05) and further increased in the cAF group (269 [199-423], P < .05 versus pAF and SR groups). ANP/BNP ratio was lower in the pAF and cAF groups than in the SR group (.6 [.5-1.2] and .7 [.5-1.0] versus 1.3 [.8-2.4], both P < .05]. Multivariate analysis in the SR and pAF groups (n = 183) demonstrated that age, congestive heart failure, ANP, and BNP, but not ANP/BNP ratio, were independent predictors for detecting pAF. Receiver operating characteristic curve analysis further showed that area under the curve was similar between ANP and BNP (.76 and .80).. ANPmay be clinically useful for detecting pAF in ischemic stroke patients as well as BNP.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Atrial Natriuretic Factor; Brain Ischemia; Female; Humans; Male; Multivariate Analysis; Predictive Value of Tests; Retrospective Studies; ROC Curve; Severity of Illness Index; Stroke

Chronic infections and neuroendocrine dysfunction may be risk factors for ischemic stroke (IS). We hypothesized that selected blood biomarkers of infection (procalcitonin [PCT]), hypothalamic-pituitary-axis function (copeptin), and hemodynamic dysfunction (midregional proatrial natriuretic peptide [MRproANP]) are associated with incident IS risk in the multiethnic, urban Northern Manhattan Study (NOMAS) cohort.. A nested case-control study was performed among initially stroke-free participants. Cases were defined as first IS (n=172). We randomly selected controls among those who did not develop an event (n=344). We calculated Cox proportional hazards models with inverse probability weighting to estimate the association of blood biomarkers with risk of stroke after adjusting for demographic, behavioral, and medical risk factors.. Those with PCT and MRproANP, but not copeptin, in the top quartile, compared with the lowest quartile, were associated with IS (for PCT adjusted hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.8 and for MRproANP adjusted HR, 3.5; 95% CI, 1.6-7.5). The associations of PCT and MRproANP differed by stroke etiology; PCT levels in the top quartile were particularly associated with small vessel stroke (adjusted HR, 5.1; 95% CI, 1.4-18.7) and MRproANP levels with cardioembolic stroke (adjusted HR, 16.3; 95% CI, 3.7-70.9).. Higher levels of PCT, a marker of infection, and MRproANP, a marker for hemodynamic stress, were independently associated with IS risk. PCT was specifically associated with small vessel and MRproANP with cardioembolic stroke risk. Further study is needed to validate these biomarkers and determine their significance in stroke risk prediction and prevention.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Brain Ischemia; Calcitonin; Case-Control Studies; Female; Glycopeptides; Humans; Male; Middle Aged; Risk Factors; Stroke

Clinical scores are recommended for predicting cardiovascular risk in patients with cerebral ischaemia to inform secondary prevention. Blood biomarkers may improve prediction beyond clinical scores.. Within the observational Find-AF trial (ISRCTN46104198), 197 patients >18 years of age with cerebral ischaemia and without atrial fibrillation had blood sampled at baseline. The predictive value of five biomarkers for a combined vascular endpoint (acute coronary syndrome, stroke, cardiovascular death) and all-cause mortality was determined, alone and in addition to the Essen Stroke Risk Score (ESRS), Stroke Prognostic Instrument 2 (SPI-2) and National Institutes of Health Stroke Scale (NIH-SS).. There were 23 vascular events (11.7%) and 13 deaths (6.6%) to 1 year follow-up. In multivariate analyses of all markers, only high-sensitivity troponin T (hsTropT) remained independently predictive for vascular events (p=0.045) and all-cause mortality (p=0.004). hsTropT was higher in patients with a vascular event (median 12.7 ng/ml vs 5.1 ng/ml), and patients with hsTropT above the median of 6.15 ng/ml had vascular events more frequently (HR 3.86, p=0.008). For prediction of vascular events as well as all-cause mortality, hsTropT significantly improved multivariate Cox regression models with ESRS, SPI-2 or NIH-SS. The c-statistic increased non-significantly from 0.695 (ESRS) or 0.710 (hsTropT) to 0.747 (ESRS+hsTropT) and from 0.699 (SPI-2) to 0.763 (SPI-2+hsTropT). No patient with a low-risk ESRS and an hsTropT below the median had a vascular event or died.. hsTropT predicts vascular events and all-cause mortality in patients with acute cerebral ischaemia and improves prediction beyond established clinical scores.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Brain Ischemia; Cardiovascular Diseases; Cohort Studies; Endpoint Determination; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Growth Differentiation Factor 15; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Stroke; Survival Analysis; Troponin; Troponin T

Adrenomedullin (AM), a vasorelaxant peptide, is secreted into the cerebrospinal fluid (CSF) from the choroid plexus and can exert natriuretic effects in the kidney. CSF AM concentration is elevated 7-10 days after the onset of aneurysmal subarachnoid hemorrhage (SAH). The aim of the present study was to determine whether CSF AM concentrations correlate with hyponatremia and delayed ischemic neurological deficits (DIND) after SAH.. CSF and plasma concentrations of AM, brain natriuretic peptide, and atrial natriuretic peptide concentrations were measured in 32 patients with SAH who underwent aneurysmal clipping within 48 h of onset. CSF and blood samples were obtained from these patients during the early period (days 1-3, day 0 being regarded as the day of SAH onset) and the late period (days 8-10).. In all patients, AM concentration during the early and late periods was significantly higher in the CSF than in the plasma (p = 0.0028 and p < 0.0001). In addition, CSF AM concentration was significantly higher during the late period than during the early period (p < 0.0001). Hyponatremia (plasma sodium <135 mmol/l) was present in 11 patients (34.4%) during the late period, and DIND developed in 6 patients (19%) between day 5 and day 13. Logistic regression analysis demonstrated that late-period CSF AM concentration correlated with hyponatremia and DIND (95% CI: 1.003-1.069, p = 0.0074 and 95% CI: 1.003-1.052, p = 0.0108).. The present study demonstrated that CSF AM during the late period following SAH correlates with hyponatremia and DIND.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Brain Ischemia; Case-Control Studies; Cohort Studies; Female; Humans; Hyponatremia; Intracranial Aneurysm; Male; Middle Aged; Natriuretic Peptide, Brain; Subarachnoid Hemorrhage; Time Factors

A precise definition of genetic factors responsible for common forms of stroke is still lacking. The purpose of the present study was to investigate the contributory role of the genes encoding atrial natriuretic peptide (ANP) and type A natriuretic peptide receptor (NPRA) in humans' susceptibility to develop ischemic stroke.. Allele and genotype frequencies of ANP and NPRA were characterized in an Italian case-control study with patients affected by vascular disease or risk factors. Subjects were recruited from the island of Sardinia (206 cases, 236 controls).. A significant association between the ANP/TC2238 polymorphic site and stroke occurrence was found when a recessive model of inheritance was assumed. The risk conferred by this mutant genotype, when estimated by multivariate logistic regression analysis, was 3.8 (95% confidence interval, 1.4 to 10.9). A significantly increased risk of stroke recurrence was observed among cases carrying the ANP/CC2238 genotype compared with cases carrying the ANP/TT2238 genotype (P=0.04). No direct association of NPRA with stroke occurrence was detected. However, a significant epistatic interaction between the ANP/CC2238 genotype and an allelic variant of NPRA led to a 5.5-fold increased risk of stroke (95% confidence interval, 1.5 to 19.4).. Our findings support a direct contributory role of ANP to stroke in humans. A significant interaction between ANP and NPRA on stroke occurrence was found.

Topics: Aged; Atrial Natriuretic Factor; Brain Ischemia; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Guanylate Cyclase; Humans; Male; Middle Aged; Mutation; Polymorphism, Genetic; Receptors, Atrial Natriuretic Factor; Recurrence; Stroke

Cortical spreading depression (CSD) is characterised by slowly propagating waves of cellular depolarization and depression and involves transient changes in blood flow, ion balance and metabolism. In cerebral ischaemia, peri-infarct CSD-like depolarization potentiates infarct growth, whereas preconditioning with a CSD episode protects against subsequent ischaemic insult. Thus, many of the long-lasting molecular changes that occur in CSD-affected tissue are presumed to be part of a 'neuroprotective cascade.' 3',5'-Cyclic guanosine monophosphate (cGMP) has been shown to be a neuroprotective mediator and the nitric oxide system, which increases cGMP production by soluble guanylate cyclase, is up-regulated by CSD. Atrial and C-type natriuretic peptide (ANP/CNP) are present in cerebral cortex and their actions are mediated via particulate guanylate cyclase receptors and cGMP production. Therefore, in further efforts to characterise the role of cGMP-related systems in CSD and neuroprotection, this study investigated possible changes in cortical natriuretic peptide expression following acute, unilateral CSD in rats. Using in situ hybridisation, significant 20-80% increases in ANP mRNA were detected in layers II and VI of ipsilateral cortex at 6 h and 1-14 days after CSD. Ipsilateral cortical levels were again equivalent to control contralateral values after 28 days. Assessment of cortical concentrations of ANP immunoreactivity by radioimmunoassay revealed a significant 57% increase at 7 days after CSD. Despite using a sensitive signal-amplification protocol, authentic ANP-like immunostaining was readily detected in subcortical nerve fibres, but was not reliably detected in normal or CSD-affected neocortex, suggesting the presence of very low levels, and/or active or differential processing of the peptide. Cortical CNP mRNA levels are not altered by CSD, indicating the specificity of the observed effects.Overall, these novel findings demonstrate a prolonged increase in cortical ANP expression after an acute episode of CSD. The overlap between the described time course of CSD-induced protection against ischaemic insult and demonstrated increases in ANP levels, suggest that ANP (like nitric oxide) may contribute to CSD-induced neuroprotection, via effects on cGMP production and other signal-transduction pathways.

Topics: Animals; Atrial Natriuretic Factor; Brain Ischemia; Cell Survival; Cerebral Cortex; Cerebral Infarction; Cortical Spreading Depression; Cyclic GMP; Gene Expression; Ischemic Preconditioning; Male; Neurons; Potassium Chloride; Rats; Rats, Sprague-Dawley; Reaction Time; RNA, Messenger; Signal Transduction; Up-Regulation

The atrial natriuretic peptide (ANP) gene may underlie stroke susceptibility and sensitivity to cerebral ischemia in an animal model of stroke. The authors investigate its role in humans by genotyping a polymorphism (G664A) in 436 patients with ischemic cerebrovascular disease and 295 community control subjects. The frequency of this variant was similar in both groups and across the different stroke subtypes. The ANP gene G664A polymorphism is therefore unlikely to be an important risk factor for ischemic stroke in this population.

Topics: Aged; Atrial Natriuretic Factor; Brain Ischemia; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Stroke

-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.

Topics: Amino Acid Substitution; Animals; Atrial Natriuretic Factor; Base Sequence; Brain; Brain Ischemia; Cells, Cultured; Cerebrovascular Disorders; Chromosome Mapping; DNA Primers; Exons; Genetic Markers; Genetic Predisposition to Disease; Hypertension; Introns; Male; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Point Mutation; Polymerase Chain Reaction; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley

Ischaemic stroke is a complex disorder caused by a combination of genetic and environmental factors. Clinical and epidemiological studies have provided strong evidence for genetic influences in the development of human stroke and several mendelian traits featuring stroke have been described. The genetic analysis of the non-mendelian, common ischaemic stroke in humans is hindered by the late onset of the disease and the mode of inheritance, which is complex, polygenic and multifactorial. An important approach to the study of such polygenic diseases is the use of appropriate animal models in which individual contributing factors can be recognized and analysed. The spontaneously hypertensive stroke-prone rat (SHRSP) is an experimental model of stroke characterized by a high frequency of spontaneous strokes as well as an increased sensitivity to experimentally induced focal cerebral ischaemia. Rubattu et al. performed a genomewide screen in an F2 cross obtained by mating SHRSP and SHR, in which latency to stroke on Japanese rat diet was used as a phenotype. This study identified three major quantitative trait loci (QTLs), STR-1-3. Of these, STR-2 and 3 conferred a protective effect against stroke in the presence of SHRSP alleles and STR-2 co-localized with the genes encoding for atrial natriuretic and brain natriuretic factors. Our investigation was designed to identify the genetic component responsible for large infarct volumes in the SHRSP in response to a focal ischaemic insult by performance of a genome scan in an F2 cross derived from the SHRSP and the normotensive reference strain, WKY rat. We identified a highly significant QTL on rat chromosome 5 with a lod score of 16.6 which accounts for 67% of the total variance, co-localizes with the genes encoding atrial and brain natriuretic factor and is blood pressure independent.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Brain Ischemia; Cerebral Arteries; Cerebrovascular Disorders; Chromosome Mapping; Crosses, Genetic; Disease Models, Animal; Female; Humans; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY

The effect of intraventricular atrial natriuretic peptide (ANP) on elevated intracranial pressure (ICP) was evaluated in a rodent model of global ischemia and reperfusion. ANP administration into the lateral ventricle 30 minutes after reperfusion statistically significantly reduced ICP compared with both vehicle treated animals (p < 0.001) and pretreatment pressures (p < 0.001). The ICP effects of ANP did not coincide with specific changes in regional perfusion parameters measured by laser-Doppler flowmetry. Two different vehicles for ANP were used to verify that the changes in ICP observed were independent of the sodium content administered in the vehicle. Based on the reductions observed in ICP, ANP deserves further evaluation as a treatment modality for the acute elevations in ICP associated with ischemic brain injury.

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Blood Flow Velocity; Blood Volume; Brain; Brain Ischemia; Cerebrovascular Circulation; Female; Injections, Intraventricular; Intracranial Hypertension; Intracranial Pressure; Rats; Rats, Sprague-Dawley; Reperfusion

Cultured vascular endothelial and smooth muscle cells actively produce adrenomedullin, a novel vasodilator peptide discovered in human pheochromocytoma tissue. This present study was designed to determine whether the plasma level of adrenomedullin is a useful indicator for estimating the degree of endothelial injury in patients with atherosclerotic disease.. We used a radioimmunoassay to measure plasma adrenomedullin concentrations in 51 patients with chronic cerebrovascular disease (34 infarctions and 17 haemorrhages) and in 10 subjects without symptomatic cerebrovascular disease. We also measured the plasma concentrations of thrombomodulin and endothelin as markers of endothelial injury. The patients were divided into three groups (A, B, and C) on the basis of the number of risk factors for atherosclerosis: hypertension, hyperlipidemia, smoking, low HDL-cholesterol, diabetes mellitus, and hyperuricaemia. Group A (68.7+/-2.7 years) consisted of patients with 0 or 1 risk factors; B (68.3+/-4.2 years) those with 2 risk factors; and C (69.2+/-3.6 years) those with 3 or more risk factors.. The plasma concentration of adrenomedullin in these patients showed a significant positive correlation with age (r=0.33, p<0.05), as well as with the plasma concentrations of thrombomodulin (r=0.54, p<0.001) and endothelin (r=0.53, p<0.001). Moreover, the plasma concentrations of adrenomedullin and thrombomodulin (p<0.005 and p<0.02, respectively) tended to be higher in Group B and to be significantly higher in Group C as compared to Group A. Plasma adrenomedullin concentrations did not, however, significantly differ between the infarction and haemorrhage patients.. These findings suggest that the plasma adrenomedullin concentrations reflect the degree of endothelial injury in patients with atherosclerotic disease.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Urea Nitrogen; Brain Ischemia; Cerebral Angiography; Cerebral Hemorrhage; Cholesterol; Chronic Disease; Endothelins; Female; Humans; Intracranial Arteriosclerosis; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptides; Risk Factors; Thrombomodulin; Tomography, X-Ray Computed; Vasodilator Agents

We examined the effect of atrial natriuretic peptide on cerebral edema in 96 rats. Forty-four rats were given 30 (n = 11), 120 (n = 26), or 150 (n = 7) micrograms/kg of the peptide intravenously over 24 hours after occlusion of the left middle cerebral artery to induce cerebral ischemia. We then measured the brain water content, the brain sodium and potassium contents, the in vitro proton nuclear magnetic resonance longitudinal (T1) and transverse (T2) relaxation times, and the area of the edematous regions. Compared with saline treatment (n = 39), peptide treatment decreased the brain water content in a dose-dependent manner and decreased the brain sodium content significantly (p less than 0.05). Peptide treatment also suppressed the lengthening of both T1 and T2 in edematous tissue (p less than 0.05 and p less than 0.01, respectively) and reduced the area of the edematous regions observed by magnetic resonance imaging (p less than 0.01). Atrial natriuretic peptide appears to have a pharmacological effect on ischemic brain edema, possibly by suppressing the elevation of water content through regulation of electrolyte transport in the brain.

Topics: Animals; Atrial Natriuretic Factor; Body Water; Brain; Brain Edema; Brain Ischemia; Magnetic Resonance Imaging; Male; Potassium; Rats; Rats, Inbred Strains; Sodium; Sodium Chloride

We investigated the effect of intraventricularly administered atrial natriuretic peptide (ANP) on the brain water, sodium and potassium contents in ischaemic brain oedema. Global ischaemia (15 min) followed by recirculation (30 min) produced by a three vessel occlusion in the rat served as a model for induction of ischaemic cerebral oedema. Water content was measured by a drying-weighing method. Sodium and potassium contents were measured by means of flame photometry. The effect of ANP was evaluated by comparing these parameters of the ANP-treated group (5 micrograms/kg and 10 micrograms/kg atriopeptin) with those of the control group (administration of 0.9% NaCL). ANP did not significantly change the content of water, sodium and potassium in the preischaemic or ischaemic brain. Intraventricularly administered ANP (5 micrograms/kg and 10 micrograms/kg) caused significant decrease in the brain water (p less than 0.02) and sodium (p less than 0.01) contents after 15 min of ischaemia and 30 min of recirculation, while the brain potassium content remained unaltered. Serum osmolality, and sodium and potassium concentrations were not influenced by administration of ANP. Accordingly, ANP acts directly on the central nervous system to inhibit brain water and sodium accumulation in ischaemic brain oedema.

Topics: Animals; Atrial Natriuretic Factor; Body Water; Brain; Brain Edema; Brain Ischemia; Injections, Intraventricular; Male; Osmolar Concentration; Potassium; Rats; Rats, Inbred Strains; Sodium

The effect of atrial natriuretic peptide (ANP) on cerebral oedema in rats was examined by magnetic resonance (MR). After occlusion of the left middle cerebral artery (MCA) to induce cerebral ischaemia, rats received continuous infusion of ANP for 24 h at a total dose of 120 micrograms/kg or 150 micrograms/kg. Proton relaxation times (T1 and T2) of excised oedematous tissue were measured in vitro and the area of the oedematous region was determined in vivo by the use of magnetic resonance imaging (MRI). The administration of ANP was found to decrease the lengthening of both T1 and T2 in the oedematous tissues and shown by MRI to decrease the area of the oedematous region, compared with group receiving saline. The topographic observations in vivo suggest that ANP suppress the development of the oedematous region.

Topics: Animals; Atrial Natriuretic Factor; Body Water; Brain; Brain Edema; Brain Ischemia; Magnetic Resonance Imaging; Male; Rats; Rats, Inbred Strains