atrial-natriuretic-factor and Cerebral-Hemorrhage

Patients with hyponatremia of central origin were treated with a mineralocorticoid, and the pathogenetic mechanism of the hyponatremia was assessed based on the therapeutic effect obtained. The subjects were 14 patients (6 with subarachnoid hemorrhage, 3 with hypertensive intracerebral hemorrhage, 2 with cerebral infarct and 3 with head injury) who developed hyponatremia, as a complication during their hospital stay for their intracranial lesions from April to December 1992. Patients with serum Na levels below 135 mEq/l for more than 2 days with no other discernible etiology were defined as having hyponatremia of central origin. The mineralocorticoid used was fludrocortisone acetate, and as a rule administration was started the day after the onset of hyponatremia. When improvements occurred within 3 days, in 3 to 7 days, or 8 days or more efficacy was rated "excellent", "good" or "poor", respectively. The mean interval until the onset of hyponatremia was 10.4 days, its mean duration was 5.7 days, and the mean minimum serum sodium level was 129.5 mEq/l. The dose of fludrocortisone administration was 0.1 mg/day except for one patient who was treated with 0.3 mg/day. The mean period of administration was 3.7 days (range: 3 to 6 days), and the route was via a stomach tube in 5 cases and oral in 9 cases. The therapeutic effect was excellent in 9 cases, good in 3 cases and poor in 2 cases, the efficacy rate being 86%. None of the patients manifested side effects. Plasma atrial natriuretic peptide levels were above 100 pg/ml in 2 patients and 50-100 pg/ml in 8 patients and neither of the former 2 patients exhibited "excellent" efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Brain Diseases; Cerebral Hemorrhage; Cerebral Infarction; Female; Fludrocortisone; Humans; Hyponatremia; Male; Middle Aged; Sodium; Subarachnoid Hemorrhage

Plasma kallikrein (PKa) has been implicated in contributing to hemorrhage following thrombolytic therapy; however, its role in spontaneous intracerebral hemorrhage is currently not available. This report investigates the role of PKa on hemorrhage and hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were fed with a high salt-containing stroke-prone diet to increase blood pressure and induce intracerebral hemorrhage. The roles of PKa on blood pressure, hemorrhage, and survival in SHRSP were examined in rats receiving a PKa inhibitor or plasma prekallikrein antisense oligonucleotide (PK ASO) compared with rats receiving control ASO. Effects on PKa on the proteolytic cleavage of atrial natriuretic peptide (ANP) were analyzed by tandem mass spectrometry. We show that SHRSP on high-salt diet displayed increased levels of PKa activity compared with control rats. Cleaved kininogen was increased in plasma during stroke compared to SHRSP without stroke. Systemic administration of a PKa inhibitor or PK ASO to SHRSP reduced hemorrhage and blood pressure, and improved neurological function and survival compared with SHRSP receiving control ASO. Since PKa inhibition was associated with reduced blood pressure in hypertensive rats, we investigated the effects of PKa on the cleavage of ANP. Incubation of PKa with ANP resulted in the generation fragment ANP

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cerebral Hemorrhage; Hypertension; Plasma Kallikrein; Rats; Rats, Inbred SHR; Stroke

A prognostic biomarker that can provide a good prediction of prognosis in patients with intracerebral hemorrhage (ICH) would be beneficial in guiding the initial management decisions in the setting of ICH. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker of prognosis in patients with cardiovascular disease and ischemic stroke. However, the prognostic role of NT-proBNP in patients with spontaneous ICH is still a controversial issue. This study aimed to determine the prognostic value of NT-proBNP in patients with spontaneous ICH. A total of 132 patients from 571 ICH cases in inpatient settings were enrolled in this study. Blood samples from each subject were obtained and analyzed for NT-proBNP on admission and on days 4 and 7. The first end point was functional outcome at discharge, which was dichotomized into favorable or unfavorable; the secondary end point was mortality within 6 months after ICH. Compared with the baseline levels on admission after ICH, the NT-proBNP levels increased markedly on day 4 (P < 0.05). Multivariate logistic regression analysis indicated that the NT-proBNP level on day 4, the ICH score, and the APACHE II score were independent prognostic factors of functional outcome and 6-month mortality in ICH patients. A cutoff NT-proBNP level of 999.85 pg/ml predicted an unfavorable functional outcome (with 66.1% sensitivity and 98.7% specificity) and 6-month mortality (with 93.8% sensitivity and 92.0% specificity) in ICH patients. Thus, the NT-proBNP level on day 4 was found to be a powerful prognostic predictor of functional outcome and 6-month mortality in ICH patients, which would be beneficial to guiding the initial management decisions in the setting of ICH.

Topics: Aged; Analysis of Variance; Atrial Natriuretic Factor; Cerebral Hemorrhage; Cohort Studies; Female; Glasgow Coma Scale; Humans; Inpatients; Male; Middle Aged; Protein Precursors

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

Atrial natriuretic peptide (ANP) and arginine vasopressin regulate brain water and electrolytes. Treatment with ANP at the onset of a hemorrhagic injury reduces edema. Clinically, however, hemorrhagic masses form too rapidly for preventive treatment. Therefore, we measured the effect of ANP on brain edema after the hemorrhagic mass was formed.. Adult rats had hemorrhagic lesions produced by the intracerebral injection of 0.4 U bacterial collagenase. Four hours later, an infusion of ANP (120 or 700 ng/kg per 20 hours) was begun into the peritoneum using an implanted miniosmotic pump. Twenty-four hours after the injury, brain water and electrolyte values were measured. The mechanism of ANP action was explored in other groups of rats that either had osmolality increased with mannitol or were injected with the cyclic GMP analogue, 8-bromo-cGMP.. Atrial natriuretic peptide given after a 4-hour delay significantly reduced brain water and sodium 24 hours after the injury (P < .05). However, neither mannitol nor 8-bromo-cGMP affected brain edema.. Delayed administration of ANP reduces brain edema secondary to a hemorrhagic mass. Because it is effective after the mass has formed, ANP may be useful in treatment of edema secondary to intracranial bleeding.

Topics: Animals; Atrial Natriuretic Factor; Brain; Brain Edema; Cerebral Hemorrhage; Collagenases; Rats; Rats, Sprague-Dawley; Time Factors

In order to assess the central effects of gamma-aminobutyric acid (GABA) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular function, the following two experiments (Exp) were carried out in conscious rats (n = 24). Experiment I: GABA (10 micrograms/kg.min) was intracerebroventricularly (i.c.v.) administered into conscious rats receiving an intravenous (i.v.) infusion of 2.5 M NaCl, and the vehicle alone was i.c.v. administered under i.v. 2.5 M NaCl in the control group. Experiment II: GABA (12 micrograms/kg.min) was infused i.c.v. in conscious rats during hemorrhage (1.6% of BW) and the vehicle alone was i.c.v. administered during hemorrhage in the control study. In Experiment I, plasma AVP and ANP and mean arterial blood pressure (MABP) increased in response to 2.5 M NaCl, but heart rate (HR) slightly decreased. I.C.V. GABA attenuated the AVP and ANP responses, but did not affect MABP and HR. In Experiment II, plasma AVP increased due to decreases in MABP induced by hemorrhage, but plasma ANP and HR never changed. I.C.V. GABA did not affect plasma AVP and ANP, MABP and HR. These results show that i.c.v. GABA has an inhibitory effect on AVP and ANP release in response to hypertonic NaCl, but not to hemorrhage, but never affected hypertonic NaCl-induced increases in blood pressure.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Cerebral Hemorrhage; gamma-Aminobutyric Acid; Hematocrit; Injections, Intraventricular; Male; Osmolar Concentration; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Saline Solution, Hypertonic

Plasma atrial natriuretic peptide (ANP) was measured with radioimmunoassay in 39 patients with acute stroke. The mean level was 144.3 +/- 8.7 pg/ml; this was significantly higher in comparison with those in normal controls (55.8 +/- 4.7 pg/ml, n = 20) and hypertension patients (87.7 +/- 8.0 pg/ml, n = 15). Serial measurement of ANP level in 6 patients showed that it was elevated on the first day of the stroke, reached to its peak on the second or third day and returned to normal after two weeks. Five patients had hyponatremia following the attack of stroke and the plasma ANP level was further elevated. It is suggested that elevated plasma ANP level might be a pathogenetic factor of the accompanying hyponatremia in stroke.

Topics: Aged; Atrial Natriuretic Factor; Cerebral Hemorrhage; Cerebral Infarction; Female; Humans; Hyponatremia; Male; Middle Aged; Radioimmunoassay

The concentrations of atrial natriuretic peptide (ANP) in atria, hypothalami and plasma were investigated in relation to the variations of the plasma endogenous immunoreactive arginine vasopressin (Ir-AVP) during water deprivation or hemorrhage in normal conscious Wistar rats. Furthermore, the in vitro and in vivo effect of extracellular hyperosmolarity on ANP release from right atrium and hypothalamus was examined. Water deprivation elevated circulating immunoreactive ANP (Ir-ANP: pg/ml) to 153 +/- 7 (24 h); 174 +/- 1 (48 h) from the control level (109.6 +/- 7.8). This increase in Ir-ANP concentration which correlated with atrial (r = -0.93) or hypothalamic (r = -0.87) Ir-ANP content decrease, was associated with significantly enhanced levels of plasma Ir-AVP, plasma sodium, osmolarity and hematocrit. An acute volume depletion by hemorrhage significantly reduced plasma Ir-ANP (67 +/- 8.4 pg/ml) from the sham operated level (140 +/- 18 pg/ml). Plasma Ir-AVP was elevated dramatically (207.4 +/- 53.4 pg/ml) compared with the sham operated level (8.8 +/- 2.6 pg/ml). These results, indicating the lack of correlation between plasma Ir-ANP and Ir-AVP in vivo, suggest that the ANP secretion, which is regulated mainly by plasma volume, may be modulated by a change in plasma osmolarity. Extracellular hyperosmolarity stimulated the ANP release from superfused sliced normal rat atria and hypothalami.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Volume; Cerebral Hemorrhage; Heart; Heart Atria; Hypothalamus; Male; Myocardium; Osmolar Concentration; Radioimmunoassay; Rats; Rats, Wistar; Water Deprivation

Injection of arginine vasopressin into the cerebral ventricles in animals with brain injury increased brain water, whereas injection of atrial natriuretic peptide reduced water content. Therefore, to determine the role of endogenous arginine vasopressin in brain edema, we attempted to inhibit edema from a hemorrhagic lesion with an arginine vasopressin V1 receptor antagonist or atrial natriuretic peptide.. Adult Sprague-Dawley rats with hemorrhages induced by 0.4 IU bacterial collagenase were treated with 75 ng (n = 9) or 8 micrograms (n = 9) of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)Arg, 3.2 micrograms (n = 4) atrial natriuretic peptide injected intracerebrally, or 5 micrograms/kg per hour (n = 7) atrial natriuretic peptide intraperitoneally. They were compared with control groups injected with 0.4 IU collagenase only. Brain water and electrolytes were measured 24 hours later. Brain uptake of [14C]sucrose was measured 30 minutes after lesions were induced by 0.4 IU collagenase alone (n = 5) or after collagenase injection and 50 micrograms/kg per hour (n = 5) atrial natriuretic peptide injected intravenously.. The arginine vasopressin V1 receptor antagonist and atrial natriuretic peptide significantly (p < 0.05) reduced water and sodium contents in the posterior edematous regions. Brain uptake of [14C]sucrose was significantly reduced by intravenous atrial natriuretic peptide.. Antagonists to arginine vasopressin V1 receptors and atrial natriuretic peptide both significantly reduce hemorrhagic brain edema, and atrial natriuretic peptide appears to protect the blood-brain barrier.

Topics: Angiotensin Receptor Antagonists; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood-Brain Barrier; Body Water; Brain Edema; Cerebral Hemorrhage; Collagenases; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Sodium; Sucrose; Vasopressins

The results of the present study demonstrate that atrial natriuretic factor (ANF) in the mammillary bodies has a dynamic change, while ANF in the median eminence is relatively constant in the course of the increase of blood pressure. It suggests that ANF in the mammillary bodies might take part in the regulation of blood pressure and ANF in the median eminence mainly participates in the functional regulation of the adenohypophysis.

Topics: Animals; Atrial Natriuretic Factor; Cerebral Hemorrhage; Hypertension; Male; Mammillary Bodies; Median Eminence; Rats; Rats, Inbred SHR; Rats, Inbred Strains

The comparative biological activities of intracerebroventricular (icv) injection of alpha-rat and alpha-human atrial natriuretic peptide (rANP and hANP, respectively) in the arginine vasopressin (AVP) release in conscious rats and the binding properties of these peptides to their specific receptors have been investigated. An icv injection of 5 micrograms rANP inhibited the AVP release induced by osmotic and hemorrhagic stimuli. In contrast, 20 micrograms of hANP was needed to exert an inhibitory effect on the AVP release. The receptor binding studies were carried out by using rat hypothalamic membrane preparations. The binding studies revealed that the potency of rANP was greater than that of hANP in displacing radioligand from its binding sites. Scatchard analysis revealed that the dissociation constant for rANP was significantly lower than that for hANP (0.52 +/- 0.04 vs 1.20 +/- 0.16 nM, P less than 0.01). The binding capacity of these peptides was similar. These results suggest that the greater biological potency of rANP compared with hANP in the inhibition of AVP release is caused by the difference in the binding potency of these peptides.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Cerebral Hemorrhage; Cerebrospinal Fluid; Humans; Hypertonic Solutions; Hypothalamus; Male; Radioimmunoassay; Rats; Rats, Inbred Strains; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface