Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain edema formation is one of the most important mechanisms responsible for brain damage after ischemic stroke. Despite considerable efforts, no specific therapy is available yet. Arginine vasopressin (AVP) regulates cerebral water homeostasis and has been involved in brain edema formation. In the current study, we investigated the role of AVP V1 and V2 receptors on brain damage, brain edema formation, and functional outcome after transient focal cerebral ischemia, a condition comparable with that of stroke patients undergoing thrombolysis. C57/BL6 mice were subjected to 60-min middle cerebral artery occlusion (MCAO) followed by 23 h of reperfusion. Five minutes after MCAO, 100 or 500 ng of [deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-vasopressin (AVP V1 receptor antagonist) or [adamantaneacetyl(1), O-Et-D-Tyr(2), Val(4), Abu(6), Arg(8,9)]-vasopressin (AVP V2 receptor antagonist) were injected into the left ventricle. Inhibition of AVP V1 receptors reduced infarct volume in a dose-dependent manner by 54% and 70% (to 29+/-13 and 19+/-10 mm3 versus 63+/-17 mm3 in controls; P<0.001), brain edema formation by 67% (to 80.4%+/-1.0% versus 82.7%+/-1.2% in controls; P<0.001), blood-brain barrier disruption by 75% (P<0.001), and functional deficits 24 h after ischemia, while V2 receptor inhibition had no effect. The current findings indicate that AVP V1 but not V2 receptors are involved in the pathophysiology of secondary brain damage after focal cerebral ischemia. Although further studies are needed to clarify the mechanisms of neuroprotection, AVP V1 receptors seem to be promising targets for the treatment of ischemic stroke.
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PMID:Role of arginine vasopressin V1 and V2 receptors for brain damage after transient focal cerebral ischemia. 1574 46

Ischemia-induced brain edema formation is mediated by increased transport of Na and Cl across an intact blood-brain barrier (BBB). Our previous studies have provided evidence that a luminally located BBB Na-K-Cl cotransporter is stimulated during cerebral ischemia to increase transport of Na and Cl into the brain. The main focus of the present study was to evaluate the effects of arginine vasopressin (AVP), previously shown to be increased in the brain during ischemia and to promote edema formation, on activity of the BBB cotransporter. Cerebral microvascular endothelial cell (CMEC) monolayers were cultured in astroglial cell conditioned medium, and Na-K-Cl cotransporter activity was assessed as bumetanide-sensitive (86)Rb influx. In both human and bovine CMECs, as well as in freshly isolated microvessels, AVP stimulated cotransport activity. This stimulatory effect was mimicked by V(1) but not V(2) vasopressin agonists and was blocked by V(1) but not V(2) vasopressin antagonists. Consistent with a V(1) vasopressin receptor mechanism of action, AVP caused an increase in CMEC intracellular [Ca] that was blocked by a V(1) antagonist. Exposing the cells to [Ca]-free media and/or reducing intracellular [Ca] by BAPTA also blocked AVP stimulation of CMEC cotransporter activity, as did the phospholipase C inhibitor U-73122. Finally, we found that while stimulation of CMEC cotransporter activity by AVP occurred within minutes, it was also sustained for hours in the continued presence of AVP. These findings support the hypothesis that AVP, through a V(1) receptor- and [Ca]-dependent mechanism, stimulates the BBB Na-K-Cl cotransporter to participate in ischemia-induced edema formation.
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PMID:Arginine vasopressin stimulation of cerebral microvascular endothelial cell Na-K-Cl cotransporter activity is V1 receptor and [Ca] dependent. 1580 57

The brain and the peripheral (hormonal) angiotensin II systems are stimulated during stress. Activation of brain angiotensin II AT(1) receptors is required for the stress-induced hormone secretion, including CRH, ACTH, corticoids and vasopressin, and for stimulation of the central sympathetic activity. Long-term peripheral administration of the angiotensin II AT(1) antagonist candesartan blocks not only peripheral but also brain AT(1) receptors, prevents the hormonal and sympathoadrenal response to isolation stress and prevents the formation of stress-induced gastric ulcers. The mechanisms responsible for the prevention of stress-induced ulcers by the AT(1) receptor antagonist include protection from the stress-induced ischemia and inflammation (neutrophil infiltration and increase in ICAM-1 and TNF-alpha) in the gastric mucosa and a partial blockade of the stress-induced sympathoadrenal stimulation, while the protective effect of the glucocorticoid release during stress is maintained. AT(1) receptor antagonism prevents the stress-induced decrease in cortical CRH(1) and benzodiazepine binding and is anxiolytic. Blockade of brain angiotensin II AT(1) receptors offers a novel therapeutic opportunity for the treatment of anxiety and other stress-related disorders.
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PMID:Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists. 1583 32

Since the discovery of atrial natriuretic peptide (ANP) more than 20 years ago, numerous studies have focused on the mechanisms regulating ANP secretion. From a physiological standpoint, the most important factor governing ANP secretion is mechanical stretching of the atria, which normally occurs when extracellular fluid volume or blood volume is elevated. In addition, the ability of several vasoconstrictors to increase ANP secretion can be traced to their indirect effects on atrial stretch via increases in cardiac preload or afterload. Whether vasoconstrictors such as angiotensin II and vasopressin have a direct positive or negative effect on ANP secretion has not been determined with certainty. Two paracrine factors derived from endothelial cells play important roles in modulating ANP secretion. Endothelin, a potent vasoconstrictor, stimulates ANP secretion and augments stretch induced ANP secretion. The dramatic increase in ANP release produced by cardiac ischemia appears to be mediated in part by endothelin. Nitric oxide (NO), an important vasodilator, is also produced by endothelial cells and inhibits ANP secretion acting through cyclic GMP as an intracellular messenger. Several recent studies have helped to define the cellular mechanism contributing to regulation of ANP secretion including stretch-activated ion channels, prostaglandins, cytochrome P450, G proteins and cell calcium. A number of steps in the cellular transduction of the ANP signal remain to be resolved. The release of ANP in disease states such as myocardial infarction and heart failure appears to be related to both mechanical and cellular events.
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PMID:Mechanisms of atrial natriuretic peptide secretion from the atrium. 1599 90

Vasoplegia as catecholamine resistent hypotension occurs in severe hemorrhagic or septic shock and post cardiopulmonary bypass. The entire rational behind this phenomenon is still unclear. An ATP-shortage in the vascular musculature, disregulation of vasopressin release, and the activation of ATP-dependent potassium-channels are discussed. In the last years, attention is drawn towards the activation of ATP-dependent potassium-channels and the possible therapeutic inhibition by glibenclamid. However, inhibition of potassium-channels does not normalize blood pressure under all circumstances. In particular in septic shock other mechanisms have to be involved. Overall, the sometimes desperate clinical situation has led to a large number of case reports und uncontrolled series of retrospectively analysed cases, where vasopressin or methylenblue were discribed as successfully reversing catecholamine resistent hypotension. Nevertheless, in hemorrhagic and septic shock scientific evidence of the clinical effects and the right dose as well as placebo controlled studies comparing the agents and possible combinations of agents are desirable but hardly available yet. In the case of severe hypotension following surgery under cardiopulmonary bypass results of the first randomized and placebo controlled studies describe successful restoration of blood pressure and even a decrease in perioperative mortality. Concerning the side effects, vasopressin and methylenblue, like most vasopressors, can cause gastrointestinal ischemia, but with the small number of patients enrolled so far, further major side effects can not be ruled out. Accordingly, the identification of risk factors for the development of vasoplegia and the prediction of the extent of the response or the rate of non-responders to these treatments are widely unknown. However, although the administration of vasopressin and methylenblue can not be recommended as a standard treatment it provides an additional option in individual cases of life threatening vasoplegia.
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PMID:[Catecholamine-resistant hypotension -- an update]. 1600 20

The hormone relaxin, known for its action on the female reproductive tract, is also able to act on organs and systems different from the reproductive ones, including the blood vessels, the heart and the brain. Relaxin causes vasodilation in several organs stimulating the biosynthetic pathway of nitric oxide (NO), a potent vasodilator. Relaxin also has a cardioprotective action: it reduces the inflammatory activation of neutrophils and their adhesion to the endothelium, and protects against myocardial injury caused by ischemia and reperfusion (I-R) in experimental animal models of myocardial infarction. Its mechanisms of action chiefly depend on the hormone's vasodilatory and anti-inflammatory properties. Recently, an additional form of relaxin has been discovered in the brain, where it has been postulated to act locally as a neurotransmitter. Relaxin, acting mainly on circumventricular organs, stimulates water drinking and vasopressin release and appears to be involved in the regulation of behavioural processes. Based on its properties on the cardiovascular system, it is possible to hypothesise that relaxin could regulate the vascular tone in the central nervous system and, going a step further, could protect the brain from IR-induced damage, possibly by an NO-mediated mechanism. This latter possibility is supported by the observation that relaxin is able to up regulate the endogenous production of NO in several target cells, as NO, at appropriate levels, is known to be involved in the protection against neural pathophysiological processes such as I-R-induced injury.
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PMID:Relaxin in vascular physiology and pathophysiology: possible implications in ischemic brain disease. 1618 Nov 16

The aim of the current study was to determine whether renal medullary oxygenation is independent of the level of cortical blood flow by testing responses to stimuli that selectively reduce blood flow in either the cortex or medulla. In anesthetized rabbits, renal arterial infusion of [Phe(2),Ile(3),Orn(8)]-vasopressin selectively reduced medullary perfusion and Po(2) (-54 +/- 24 and -50 +/- 10%, respectively) but did not significantly affect cortical perfusion or tissue oxygenation. In contrast, stimulation of the renal nerves resulted in renal cortical ischemia with reductions in total renal blood flow (-76 +/- 3% at 4 Hz), cortical perfusion (-57 +/- 17%), and cortical Po(2) (-44 +/- 12%). Medullary tissue Po(2) was reduced by -70 +/- 5% at 4 Hz, despite medullary perfusion being unaffected and distal tubular sodium reabsorption being reduced (by -83.3 +/- 1.2% from baseline). In anesthetized rats, in which renal perfusion pressure was maintained with an aortic constrictor, intravenous infusion of ANG II (0.5-5 microg. kg(-1).min(-1)) dose dependently reduced cortical perfusion (up to -65 +/- 3%; P < 0.001) and cortical Po(2) (up to -57 +/- 4%; P < 0.05). However, medullary perfusion was only significantly reduced at the highest dose (5 microg. kg(-1).min(-1); by 29 +/- 6%). Medullary perfusion was not reduced by 1 microg. kg(-1).min(-1) ANG II, but medullary Po(2) was significantly reduced (-12 +/- 4%). Thus, although cortical and medullary blood flow may be independently regulated, medullary oxygenation may be compromised during moderate to severe cortical ischemia even when medullary blood flow is maintained.
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PMID:Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow. 1621 13

Neurohumoral responses have been implicated in the pathogenesis of ischemia-evoked cerebral edema. In a well-characterized animal model of ischemic stroke, the present study was undertaken to 1) study the profile of plasma arginine-vasopressin (AVP), and 2) determine whether osmotherapy with mannitol and various concentrations of hypertonic saline (HS) solutions influence plasma AVP levels. Halothane-anesthetized adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion with the intraluminal filament technique. Plasma AVP levels (means +/- SD) were significantly elevated at 24 h (42 +/- 21 pg/ml), 48 h (50 +/- 28 pg/ml), and 72 h (110 +/- 47 pg/ml), and returned to baseline at 96 h (22 +/- 15 pg/ml) following middle cerebral artery occlusion compared with sham-operated controls (14 +/- 7 pg/ml). Plasma AVP levels at 72 h were significantly attenuated with 7.5% HS (37 +/- 8 pg/ml; 360 +/- 11 osmol/l) compared with 0.9% saline (73 +/- 6; 292 +/- 6 osmol/l), 3% HS (66 +/- 8 pg/ml; 303 +/- 12 osmol/l), or mannitol (74 +/- 9 pg/ml; 313 +/- 14 osmol/l) treatment. HS (7.5%) significantly attenuated water content in the ipsilateral and contralateral hemispheres compared with surgical shams, 0.9% saline, 3% HS, and mannitol treatments. Peak plasma AVP levels were not associated with direct histopathological injury to the anterior hypothalamus. Attenuation of brain water content with 7.5% HS treatment coincides with attenuated serum AVP levels, and we speculate that this may represent one additional mechanism by which osmotherapy attenuates edema associated with ischemic stroke.
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PMID:Plasma arginine-vasopressin following experimental stroke: effect of osmotherapy. 1661 60

There exists no pharmacological treatment for fulminating brain edema. Since evidence indicates that brain aquaporin-4 (AQP4) water channels are modulated by vasopressin V1a receptors, we examined the edema-reducing properties of the selective V1a receptor antagonist, SR49059, following middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were randomly assigned to sham procedure, vehicle, or SR49059 infusion at different dosages (each n = 6,480 microL/hr, 640 microL/hr, 720 microL/hr) and starting 60 minutes before or after MCAO. After a 2-hour period of ischemia and 2 hours of reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentration. Statistics were performed using an ANOVA followed by a Tukey post hoc analysis. SR049059 treatment reduced brain water content in the infarcted area given at 640 microL/hr (p = 0.036), 720 microL/hr 60 minutes before (p = 0.002) or 60 minutes after (p = 0.005) MCAO. The consecutive sodium shift into the brain was prevented (p = 0.001), while the potassium loss was inhibited only by pre-treatment (p = 0.003). These findings imply that in ischemia-induced brain edema, the selective V1a receptor-antagonist SR49059 inhibits brain edema and the subsequent sodium shift into brain. This substance offers a new avenue in brain edema treatment and prompts further study into AQP4 modulation.
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PMID:Protective effect of the V1a receptor antagonist SR49059 on brain edema formation following middle cerebral artery occlusion in the rat. 1667 76

The use of reflectance spectrophotometry (RS) for mucosal hemodynamic measurement relies on the recognition of changes in indexes of mucosal hemoglobin concentration and oxygen saturation. Endoscopic application in clinical studies has confirmed important observations demonstrated in animal experiments. The vasoconstriction induced by propranolol, vasopressin, glypressin, or somatostatin in the portal hypertensive gastric mucosa and the reduction of gastroduodenal mucosal perfusion by nonsteroidal anti-inflammatory drugs (NSAIDs) or smoking, mesenteric venoconstriction associated with systemic hypoxia, and acid-induced duodenal hyperemia are important examples. Prognostic predictions include the development of stress-induced gastric ulcerations in patients with significant reductions in gastric perfusion after thermal or head injury, or the demonstration of delayed gastric or duodenal ulcer healing when the hyperemia at the ulcer margin fails to materialize. In mechanical-ventilator-dependent patients with sepsis, a significantly reduced gastric mucosal RS measurement portends a grave prognosis (mortality >80%). Recent advances in technology resulted in the construction and validation of instruments for visible light spectroscopy. Measurements focused on tissue oxygen saturation demonstrated epinephrine and vessel-ligation-induced vasoconstriction, the absence of ischemia in radiation-induced rectal telangiectasias, and gut ischemia responsive to revascularization treatment. Endoscopic RS and visible light spectroscopy are suitable for assessing the role of blood flow in conditions with a lesser degree of ischemia and for testing the hypothesis that functional dyspepsia and dysmotility syndromes may be due to gut ischemia.
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PMID:Endoscopic reflectance spectrophotometry and visible light spectroscopy in clinical gastrointestinal studies. 1793 61


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