Bhardwaj Anish
Neurosciences Critical Care Division, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ann Neurol. 2006 Feb;59(2):229-36. doi: 10.1002/ana.20788.
Hyponatremia is frequently associated with neurological disease, neurosurgical procedures, and use of psychoactive drugs. Arginine vasopressin (AVP), or antidiuretic hormone, is the principal physiological regulator of water and electrolyte balance, and disruption of the normal AVP response to osmotic stimuli is a common cause of dilutional hyponatremia in neurological disorders. The hyponatremia-induced shift in water from the extracellular to the intracellular compartment can lead to cerebral edema and serious neurological complications, especially if the decrease in serum sodium concentration ([Na+]) is large or rapid. Overly rapid correction of the serum [Na+] may lead to osmotic demyelination and irreversible brain injury. Fluid restriction is considered first-line treatment and pharmacological agents currently used in the treatment of hyponatremia are limited by inconsistent response and adverse side effects. AVP receptor antagonists represent a new approach to the treatment of hyponatremia by blocking tubular reabsorption of water by binding to V2 receptors in the renal collecting ducts, resulting in aquaresis. Initial clinical experience with AVP receptor antagonists for hyponatremia has shown that these agents augment free water clearance, decrease urine osmolality, and correct serum [Na+] and serum osmolality. Controlled clinical trials now underway will help elucidate the role of AVP receptor antagonism in the treatment of hyponatremia.
低钠血症常与神经系统疾病、神经外科手术及精神活性药物的使用相关。精氨酸血管加压素（AVP），即抗利尿激素，是水和电解质平衡的主要生理调节因子，正常情况下AVP对渗透压刺激的反应遭到破坏是神经系统疾病中稀释性低钠血症的常见原因。低钠血症导致的水从细胞外间隙向细胞内间隙转移可引发脑水肿及严重的神经系统并发症，尤其是在血清钠浓度（[Na+]）大幅下降或快速下降时。血清[Na+]纠正过快可能导致渗透性脱髓鞘及不可逆的脑损伤。限水被视为一线治疗方法，而目前用于治疗低钠血症的药物因反应不一致及不良反应而受到限制。AVP受体拮抗剂是治疗低钠血症的一种新方法，它通过与肾集合管中的V2受体结合来阻断肾小管对水的重吸收，从而产生利水作用。AVP受体拮抗剂治疗低钠血症的初步临床经验表明，这些药物可增加自由水清除率、降低尿渗透压，并纠正血清[Na+]及血清渗透压。目前正在进行的对照临床试验将有助于阐明AVP受体拮抗作用在低钠血症治疗中的作用。
