Arginine vasopressin V1-antagonist and atrial natriuretic peptide reduce hemorrhagic brain edema in rats.

Abstract

Background and Purpose: 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 V t receptor antagonist or atrial natriuretic peptide.Methods: Adult Sprague-Dawley rats with hemorrhages induced by 0.4 IU bacterial collagenase were treated with 75 ng (n=9) or 8 jug (n=9) of the vasopressin Vi receptor antagonist </(CH 2 ) s Tyr(Me)Arg, 3.2 ftg (n=4) atrial natriuretic peptide injected intracerebrally, or 5 itg/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 [ and atrial natriuretic peptide (ANP) regulate water and electrolyte homeostasis by a series of complex actions at multiple sites in the body. There is increasing evidence that they play an important role in fluid balance in the central nervous system. Intravenous injection of AVP enhanced sodium transport into the cerebrospinal fluid (CSF) and lowered CSF production. 1 -2 Intraventricular injection of AVP increased transport of labeled water from blood to brain, enhanced water movement across the arachnoid villi, increased brain water content, aggravated cold-injury edema, and increased ependymal permeability but did not alter CSF production. 3 -7 In an earlier study we showed that the intracerebral injection of AVP caused an increase in brain water content that could be inhibited by an antagonist to the V, receptor of vasopressin. 8 See Editorial Comment, p 1773Intraventricular injection of ANP reduced CSF production and lowered brain water, 910 while intraventricular or continuous intravenous infusion of ANP reduced cerebral edema secondary to ischemia. 11- 12 Recently, we developed a model of brain edema secondary to a hemorrhage produced by the intracerebral injection of bacterial collagenase. 13 This model was used to study the action of intrinsic AVP in edema production and to test the effect on edema of either an antagonist to the AVP V! receptor or ANP. Materials and MethodsOne hundred twenty-seven adult Sprague-Dawley rats (Harlan Farms, Altamont, N.Y.) weighing 250-350 g were used in the study. The method for induction of an intracerebral hemorrhage has been described. syringe, was placed in a microinfusion pump (Harvard Instruments, South Natick, Mass.). The needle was implanted 5 mm below the cortex in the left caudoputamen, and 2 fil fluid containing 0.4 IU bacterial collagenase (Type VIIs, Sigma Chemical Co., St. Louis, Mo.) with or without the agents to be tested was infused over 9 minutes. The experimental protocols, approved by the Animal Research Committees at the University of New Mexico School of Medicine and the Veterans Affairs Medical Center, conformed to the guidelines esta...

Role of Arginine Vasopressin V1 and V2 Receptors for Brain Damage After Transient Focal Cerebral Ischemia

“…Our results are well in agreement with other experimental studies showing that AVP is involved in the pathophysiology of acute brain damage, for example, after subarachnoid or intracerebral hemorrhage (Doczi et al, 1984;Rosenberg et al, 1992), cortical focal lesions (Reeder et al, 1986;Bemana and Nagao, 1999), traumatic brain injury (Armstead, 2001), global cerebral ischemia (Liu et al, 1991(Liu et al, , 1996Ikeda et al, 1997), and permanent focal cerebral ischemia (Dickinson and Betz, 1992;Shuaib et al, 2002). The amount of AVP mRNA and of AVP protein increase after experimental cerebral ischemia (Liu, 1992;Liu et al, 2000) and levels of AVP are elevated in the CSF of stroke patients (Barreca et al, 2001).…”

“…Our results show that centrally applied AVP receptor antagonists do not have an effect on blood pressure, CBF, and body temperature as also observed by others (Rosenberg et al, 1992). Hence, hypothermia or any other disturbances of animal physiology can be ruled out as a possible nonspecific mechanism of the neuroprotection observed in the current study.…”

“…Its primary action is the control of water and solute excretion in the kidney; however, AVP is also released in various parts of the brain where it may act as a neurotransmitter (Buijs, 1978;Riphagen and Pittman, 1986). In the central nervous system (CNS), AVP has multiple functions including regulation of brain water (Rosenberg et al, 1992;Bemana and Nagao, 1999), brain ion homeostasis (DePasquale et al, 1989;Cserr and Latzkovits, 1992), and regulation of cerebral microvascular resistance (Fernandez et al, 2001). The effects of AVP are mainly mediated via three seventransmembrane G-protein-coupled receptors, namely V 1a , V 1b , and V 2 .…”

Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

“…21,[24][25][26] Previous work demonstrating that vasopressin may induce brain edema 20,21,56 is supported by multiple studies showing that edema is abolished by blocking the V1aR receptors. [24][25][26][27][28][29] The present results demonstrate that V1aR inhibition accelerates the recovery of [Na + ] e supporting its potential to blunt the ionic dysfunction that leads to edematous changes. Taken together, out findings suggest that SR49059 and other V1aR inhibitors may have potential as therapeutic agents for treating cellular edema by both speeding post-injury ionic recovery and reducing injury-induced elevation of ICP following CCI.…”

“…Further, experimental models of intracerebral hemorrhage, middle cerebral artery occlusion, ischemia, and cold and traumatic brain injury have demonstrated that V1aR inhibition reduces brain edema. [22][23][24][25][26][27][28][29][30][31] The underlying mechanism of this response has been attributed to either modulation of vasopressin in the brain parenchyma 17 or its interaction with aquaporin-4 (AQP4). AQP4 is the predominant water channel in the brain and has a significant role in the pathophysiology of brain edema.…”