atrial-natriuretic-factor and Brain-Edema

The study gives an overview on the regulation of cerebral water content and of brain volume. The molecular mechanisms of the development and resolution of various oedema forms are discussed in detail. The physiological and pathophysiological role of the recently discovered molecular water channel proteins aquaporin-1 (AQP1) and aquaporin-4 (AQP4) as well as the importance of central neuroendocrine regulation by vasopressin and atriopeptin are reviewed based on the relevant literature and personal studies. Quantitative water maps based on the combination of multicompartment-T2, diffusion weighted MRI and T1 studies have proven to be powerful tools for studying new drugs against brain oedema brought about by various neuropathological conditions and for testing their efficacy both in animal experimental and clinical conditions. Non-peptide vasopressin antagonists, atriopeptin agonists and drugs targeting AQP4 are potential new families of oedema-decreasing drugs.

Topics: Animals; Aquaporin 1; Aquaporin 4; Aquaporins; Atrial Natriuretic Factor; Biological Transport; Blood Group Antigens; Brain Edema; Humans; Vasopressins; Water

Though the brain bulk has been considered to be constant in several pressure homeostasis studies, the central nervous tissue may be responsible for the accommodation of extracerebral masses exceeding the volume regulation capacity of the cerebral blood and cerebrospinal fluid. Volume buffering of the nervous tissue may even be functioning in parallel, in conjunction with the "fluid" compartments. Of the existing volume regulatory models, the following are discussed: osmotic feedback (buffering) preventing major fluid shifts in osmotic or pressure disequilibrium at the blood brain barrier (BBB), and the 4-compartment model, which under steady-state conditions can be regarded as an analogue of systemic tissue volume regulation, i.e. secretion of fluid at the BBB, bulk flow of interstitial space fluid (ISF) in the brain and absorption via the cerebrospinal fluid (CSF). The most recent data are presented, confirming that accommodation of space occupation by the nervous tissue is achieved via shrinkage of the extracerebral fluid (ECF), while the cell volume remains relatively constant. These findings confirm Hakim's classical hypothesis, based on biomechanical considerations, that the brain behaves like a sponge. The data presented in this survey point to a more general hypothesis: the brain interstitial space can vary in volume according to physiological and pathological stress, within certain bounds this being a reversible process which does not affect brain function. The potential role of the central neuro-endocrine system in brain volume regulation is discussed. Vasopressin (AVP) and atriopeptin (ANP) probably, function within the brain via a paracrine mechanism, as physiological regulators of brain cell and ISF volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood-Brain Barrier; Brain; Brain Edema; Cerebrospinal Fluid; Cerebrovascular Circulation; Extracellular Space; Humans; Intracranial Pressure; Water-Electrolyte Balance

The present study was designed to assess the relationship between the presence of focal brain aedema and serum concentrations of atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) in patients with subarachnoid haemorrhage (SAH). Serum levels of ANP and BNP were measured at six different time periods (Day 1, 2, 3, 4 to 7, 8 to 14, and 15 to 25) in 61 SAH-patients. Focal brain aedema, which was caused by an intracerebral haematoma associated with SAH or surgical complications, was found in eight SAH-patients by means of consecutive CT scans. The mean serum ANP and BNP levels in patients with focal brain aedema were significantly higher than those in patients without focal brain aedema between Days 4 and 14. These findings suggest that focal brain aedema may have some role in the pathogenesis of an excessive secretion of ANP and BNP during the subacute phase of SAH.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Brain Edema; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Statistics, Nonparametric; Subarachnoid Hemorrhage; Time Factors

Central salt wasting syndrome may be caused by pathological increases in serum natriuretic peptides after subarachnoid hemorrhage (SAH). However, it is unclear as to why the serum concentration of atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) increases in the subacute phase of SAH. The present study was designed to assess the correlation between focal brain edema and serum concentration of ANP or BNP in patients with SAH. Focal brain edema was found in 8 SAH-patients and peaked between days 4 and 7 of SAH. The mean serum ANP and BNP levels in patients with focal brain edema were significantly higher than those in patients without focal brain edema between days 4 and 14 of SAH. These results suggest that focal brain edema might correlate with increased levels of ANP and BNP in the subacute phase of SAH.

Topics: Atrial Natriuretic Factor; Brain Edema; Humans; Natriuretic Peptide, Brain; Retrospective Studies; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Vasopressins

To investigate whether dexamethasone (DXM) regulate the expression of Calcitonin gene-related peptide (CGRP), Endothelin (ET), Atrial natriuretic peptide (ANP), Angiotensin II (AII) in brain injury induced by endotoxin in rabbit.. Sixty-five New Zealand white rabbits were randomly divided into 3 subgroups: endotoxin group (A group), endotoxin + DXM group (B group) and normal saline group (C group). 100 microg/kg endotoxin was intracerebroventricularly injected in A group, endotoxin 100 microg/kg + DXM 1 mg/kg in B group and same volume of normal saline in C group as control. Neuropeptide level were detected by radioimmunoassay in variable periods (3 h, 6 h, 12 h, 24 h, 48 h, 72 h after injection) in the plasma, cerebrospinal fluid (CSF) and brain tissue (hippocampus area), and brain water content was measured by dry method.. CGRP, ET, ANP, AII concentrations in plasma, CSF and brain tissue changed in variable periods after injection. The higher or the lower neuropeptide levels were emerged on 12 - 24 hours after injection (P < 0.05 or P < 0.01), and changed remarkably in A group (P < 0.05 or P < 0.01). Brain water content were significantly higher and reached to peak level on 24 hours after injection. But there was a significantly increasing in A group compared to that of B group (P < 0.05 or P < 0.01).. The timely changes of CGRP, ET, ANP, AII were related to brain injury and brain edema induced by endotoxin, and DXM regulated the expression of neuropeptides and lighten brain edema.

Topics: Angiotensin II; Animals; Anti-Inflammatory Agents; Atrial Natriuretic Factor; Brain Edema; Brain Injuries; Calcitonin Gene-Related Peptide; Dexamethasone; Disease Models, Animal; Endothelins; Endotoxins; Female; Male; Neuropeptides; Rabbits

Inflammatory mediators have a role in the formation of cerebral oedema and there is evidence that cGMP is an important signal in vascular permeability increase. We have investigated the role and the source of cGMP in mediating the permeability response to acutely applied bradykinin and the histamine H(2) agonist dimaprit on single cerebral venular capillaries, by using the single vessel occlusion technique. We found that 8-bromo-cGMP applied acutely resulted in a small and reversible permeability increase with a log EC(50) -7.2 +/- 0.15 M. KT 5823, the inhibitor of cGMP-dependent protein kinase, abolished the permeability responses to both bradykinin and dimaprit, while zaprinast, an inhibitor of type 5 phosphodiesterase, potentiated the response to bradykinin. On the other hand, L-NMMA blocked the response to dimaprit, but not that to bradykinin. Inhibitors of soluble guanylyl cyclase, LY 85353 and methylene blue, also inhibited the permeability response to dimaprit, but not bradykinin. The permeability responses to the natriuretic peptides ANP and CNP were of similar magnitude to that of bradykinin with log EC(50) -10.0 +/- 0.33 M and -8.7 +/- 0.23 M, respectively. The natriuretic peptide receptor antagonist HS-142-1 blocked permeability responses to bradykinin as well as to ANP, and leukotriene D(4) blocked the responses to CNP and bradykinin, but not to dimaprit. In conclusion, the histamine H(2) receptor appears to signal via cGMP that is generated by a NO and soluble guanylyl cyclase, while bradykinin B(2) receptor also signals via cGMP but through particulate guanylyl cyclase.

Topics: Animals; Atrial Natriuretic Factor; Blood-Brain Barrier; Bradykinin; Brain Edema; Capillaries; Capillary Permeability; Cyclic GMP; Dimaprit; Female; Guanylate Cyclase; Histamine; Histamine Agonists; Inflammation Mediators; Male; Nitric Oxide; Pia Mater; Rats; Rats, Wistar; Receptor, Bradykinin B2; Receptors, Bradykinin; Receptors, Cytoplasmic and Nuclear; Receptors, Histamine H2; Soluble Guanylyl Cyclase; Venules

Centrally released arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) have been shown to participate in brain volume regulation. The aim of the present study was to evaluate the effects of centrally administered AVP and ANP on the time course of development of brain edema in vivo in hyponatremic rats, using diffusion-weighted magnetic resonance imaging.. We performed intracerebroventricular (ICV) administration of 120 microg AVP, 20 microg ANP, or physiological saline into the right lateral ventricle in 18 rats. Twenty-five minutes after the treatment, we induced systemic hyponatremia by the intraperitoneal administration of 140 mmol/L dextrose solution. Serial diffusion-weighted imaging scans were obtained up to 96 minutes after the start of the hyponatremia. Changes in the brain extra-to intracellular volume fraction ratio were estimated as changes in the apparent diffusion coefficient (ADC).. No change in the ADC was observed after the ICV injection of saline or AVP. The onset of hyponatremia induced a rapid and marked ADC reduction in both groups, indicating an increased intracellular space. However, the ADC decrease became significantly more pronounced in the ICV AVP group (83.3+/-4.7% of baseline level, mean +/- standard deviation) than in the saline group (93.7+/-3.3% of baseline, P < 0.001) after 78 minutes of hyponatremia. The ICV injection of ANP induced a prompt ADC increase to 111.5+/-10.0% (P < 0.05) of the baseline level, indicating a rapid reduction in the intracellular compartment. In the initial phase of hyponatremia, the ADC values in the ANP group were consistently higher than those in the saline group, decreasing finally to 86.9+/-9.6% after 96 minutes of hyponatremia.. Our findings demonstrate the opposite effects of AVP and ANP on the intracellular volume fraction of the brain during the development of cellular brain edema, with an immediate effect on ANP and a delayed effect on AVP. The results emphasize the direct effects of these hormones on the cellular volume regulatory mechanisms in the brain during the development of cerebral edema.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Brain Edema; Hyponatremia; Injections, Intraperitoneal; Male; Osmolar Concentration; Rats; Rats, Wistar; Renal Agents; Sodium

Astroglial swelling occurs in acute hyperammonemic states, including acute hepatic encephalopathy. In these conditions, the peripheral-type benzodiazepine receptor (PBR), a receptor associated with neurosteroidogenesis, is up-regulated. This study examined the potential involvement of PBRs and neurosteroids in ammonia-induced astrocyte swelling in culture. At low micromolar concentrations, the PBR antagonist PK 11195, atrial natriuretic peptide, and protoporhyrin IX, which are known to interact with the PBR, attenuated (16-100%) the effects of ammonia, whereas the PBR agonists Ro5-4864, diazepam binding inhibitor (DBI51-70), and octadecaneuropeptide exacerbated (10-15%) the effects of ammonia. At micromolar concentrations, diazepam, which interacts with both the PBR and the central-type benzodiazepine receptor (CBR), increased swelling by 11%, whereas flumazenil, a CBR antagonist, had no effect. However, at 100 nM diazepam and flumazenil abrogated ammonia-induced swelling. The neurosteroids dehydroepiandrosterone sulfate, tetrahydroprogesterone, pregnenolone sulfate, and tetrahydrodeoxycorticosterone (THDOC), products of PBR stimulation, at micromolar concentrations significantly enhanced (70%) ammonia-induced swelling. However, at nanomolar concentrations, these neurosteroids, with exception of THDOC, blocked ammonia-induced swelling. We conclude that neurosteroids and agents that interact with the PBR influence ammonia-induced swelling. These agents may represent novel therapies for acute hyperammonemic syndromes and other conditions associated with brain edema and astrocyte swelling.

Topics: Ammonia; Astrocytes; Atrial Natriuretic Factor; Benzodiazepines; Benzodiazepinones; Brain Edema; Cell Size; Clonazepam; Dehydroepiandrosterone Sulfate; Desoxycorticosterone; Diazepam; Diazepam Binding Inhibitor; Flumazenil; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; Isoquinolines; Nerve Tissue Proteins; Neuropeptides; Peptide Fragments; Pregnanolone; Pregnenolone; Protoporphyrins; Receptors, GABA-A; Steroids; Up-Regulation

Topics: Adrenocorticotropic Hormone; Animals; Atrial Natriuretic Factor; Brain; Brain Edema; Male; Nicotine; Peptide Fragments; Rats; Rats, Wistar

Atrial natriuretic peptide (ANP) is released excessively in spontaneously hypertensive rats (SHR), and vasodepression is its main effect on the blood vessels. The aim of the study was to investigate the changes in ANP secretion in the cerebral vasospasm following subarachnoid hemorrhage (SAH) in SHRs. The SAH was induced by the injection of 100 microliters of unheparinized, autologous blood into the cerebrospinal fluid (CSF), via a canule formerly inserted into the cisterna magna (CM). In the sham SAH group the SAH was imitated with 0.9% saline injection. The concentrations of ANP in the blood samples obtained in the acute and chronic stages of vasospasm were radioimmunoassayed with commercial RIA kits (Peninsula RIK 9103). It was found that both SAH and sham SAH induced a significant increase in plasma ANP in the chronic phase of vasospasm. No such changes were observed in the acute phase. This shows that the chronic cerebral vasospasm following SAH considerably enhances the ANP secretion in SHRs, probably through the increased endothelin release. These compensatory and regulatory mechanisms help prevent the development of brain oedema and the progression of vasopasm through secondary vasodilation.

Topics: Animals; Atrial Natriuretic Factor; Brain Edema; Hypoxia; Ischemic Attack, Transient; Male; Rats; Rats, Inbred SHR; Subarachnoid Hemorrhage

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

The effects of centrally administered atrial natriuretic peptide (ANP) on the brain water and electrolyte contents were investigated in a rodent subarachnoid haemorrhage (SAH) model. SAH caused statistically significant increases in the brain sodium and water contents, while the potassium content did not change significantly, indicating that the brain oedema could be classified as having a primarily vasogenic component. Two micrograms or 5 micrograms of rat ANP administered into the lateral ventricle at the time of SAH induction statistically significantly decreased the water and sodium accumulation measured 90 minutes following SAH. The same treatment did not inhibit development of brain oedema measured 3 hours following SAH. However, when 5 micrograms of ANP was administered intraventricularly at the time of SAH induction and also 90 minutes later, the brain oedema 3 hours following SAH was again reduced statistically significantly. These effects of ANP were found not to be mediated by primary changes in serum osmolality and electrolyte concentrations. The present results confirm that centrally administered ANP may act directly on the central nervous system to inhibit brain water and sodium accumulation in SAH-induced brain oedema. The potentials of influencing the central neuro-endocrine system as a novel way of the treatment of brain oedema are discussed.

Topics: Animals; Atrial Natriuretic Factor; Blood-Brain Barrier; Brain Edema; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Injections, Intraventricular; Male; Rats; Rats, Wistar; Subarachnoid Hemorrhage; Water-Electrolyte Balance

We used the method of RIA determined the contents of atrial natriuretic peptide (ANP), angiotensin II (ANG II) in plasma and brain tissues after brain injury in 70 rats. The results showed that the ANP was significantly decreased in brain tissues on 6, 72 hours after brain injury. At the same time, the plasma and brain tissues ANG II, brain water contents were significantly increased. The results suggested that the unbalance of ANP and ANG II may be related to the pathophysiological process of brain edema.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Brain; Brain Edema; Brain Injuries; Male; Rats; Rats, Sprague-Dawley

Atrial natriuretic peptide (ANP) regulates fluid and electrolyte homeostasis in the central nervous system. In this study, we evaluated the effects of ANP on brain edema, intracranial pressure (ICP) and cerebral energy metabolism in congenital hydrocephalus in rats. Brain edema, indicated by the longitudinal relaxation time (T1), was evaluated by 1H-magnetic resonance imaging (MRI). The ICP was monitored with a miniature pressure-transducer with telemetric system. Cerebral energy metabolism, indicated by PCr/Pi ratio, was measured by 31P-magnetic resonance spectroscopy (MRS). The rats were given 10 microliters of ANP in the left cerebral ventricle. Three different concentrations of ANP were given; 0.2 (group I), 2.0 (group II) and 20.0 (group III) micrograms/10 microliters, respectively. 10 microliters of saline was injected into the ventricle of the control group rats. There were no significant changes of ICP, T1 value and PCr/Pi ratio among the control group, group I and group II. In group III, in contrast, ICP decreased significantly at 20 minutes after ANP administration and stayed at this ICP level for 60 minutes. The T1 value decreased and PCr/Pi ratio increased 30 minutes after ANP administration. This study revealed that intraventricularly administered ANP could decrease ICP, reduce brain edema and improve the cerebral energy metabolism in rats with congenital hydrocephalus.

Topics: Animals; Animals, Newborn; Atrial Natriuretic Factor; Brain; Brain Edema; Cerebral Ventricles; Energy Metabolism; Hydrocephalus; Intracranial Pressure; Phosphates; Phosphocreatine; Rats; Rats, Inbred Strains; Water-Electrolyte Balance

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

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

The effects of intraventricularly administered atrial natriuretic peptide (ANP) on the brain water, sodium, and potassium contents in ischemic brain edema were investigated. By use of a three-vessel occlusion model, ischemic brain edema was produced in the rat brain by 15 minutes of global ischemia followed by recirculation. Water content was measured by means of a drying/weighing method; sodium and potassium contents were measured by means of flame photometry. The effects of intraventricular administration of ANP were evaluated by a comparison between the groups given 2 and 5 micrograms of atriopeptin II (treated) and those given 0.9% NaCl (sham-treated). The treated groups showed significant decreases in brain water (P less than 0.02) and sodium (P less than 0.01) contents at 15 and 30 minutes after recirculation, whereas the brain potassium contents remained unaltered. Before ischemia and immediately after 15 minutes of ischemia, intraventricularly administered ANP did not significantly change the brain water, sodium, or potassium contents. There was no significant difference in the effect on the amount of brain water and sodium between the two doses (2 and 5 micrograms). These effects of ANP were thought not to be mediated by primary changes in serum osmolality and sodium and potassium concentrations, because intraventricular administration of ANP did not change them significantly. The present results reveal that, in ischemic brain edema, ANP may act directly on the central nervous system to inhibit brain water and sodium accumulation.

Topics: Animals; Atrial Natriuretic Factor; Brain Edema; Male; Rats; Rats, Inbred Strains; Water-Electrolyte Balance

We examined the effect of atrial natriuretic peptide (ANP) administration on cerebral oedema in rats. Intravenous ANP infusion with total dose of 120 micrograms/kg and 100 micrograms/kg suppressed the elevation of water and Na contents in left middle cerebral artery (MCA) occluded and cold injured brain tissue, indicating that ANP has a suppressive effect on cerebral oedema. Similar ANP infusion at a low dose of 1 microgram/kg/h for 6 h also resulted in observation of the anti-oedematous effect in both models, with no observable occurrence of the known systemic effects of ANP on systolic blood pressure (SBP), heart rate (HR), hematocrit, or serum electrolyte ion (Na+, K+, Cl-) concentrations. The results thus suggest that the anti-oedematous effect of ANP is attributable to water and Na content control by ANP specific to the damaged tissue, possibly through inhibition of sodium transport. Taken together with a recent study in which it was shown that ANP might inhibit sodium transport in cerebral microvessel, our results suggest that ANP suppresses the development of brain oedema by inhibiting sodium transport and the coupled water influx.

Topics: Animals; Atrial Natriuretic Factor; Body Water; Brain Edema; Cardiovascular System; Cerebral Arteries; Cold Temperature; Constriction, Pathologic; Osmolar Concentration; Potassium; Rats; Rats, Inbred Strains; Sodium

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

Little is known about the pathophysiology of cerebral edema and other disturbances of water balance that involve the barrier tissues at the interface of blood and brain. The present experiments show that these barrier tissues contain receptors and second messenger systems for atriopeptins, recently identified cardiac peptides involved in peripheral water regulation. They also show that atriopeptins can alter the rate of cerebrospinal fluid production. Because the blood-brain and blood-cerebrospinal fluid barriers are involved in normal water movements in the central nervous system, these studies suggest that brain barrier tissues may be important end organs for the atriopeptins and that atriopeptins could have therapeutic application to disorders of water balance in the central nervous system. An isolated, purified population of atriopeptin receptor cells, obtained from choroid epithelium, was used in these experiments. This cell population may provide a valuable model system for investigating the intracellular biochemical mechanisms through which atriopeptins exert their actions.

Topics: Adenylyl Cyclases; Animals; Atrial Natriuretic Factor; Blood-Brain Barrier; Brain; Brain Edema; Brain Mapping; Choroid Plexus; Epithelium; Guanylate Cyclase; Rabbits; Rats; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Water-Electrolyte Balance