Neurological impact of vasopressin dysregulation and hyponatremia.
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.
Bhardwaj
Anish
A
Neurosciences Critical Care Division, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. bhardwaj@ohsu.edu
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D006801:Humans; D007010:Hyponatremia / Q000209:etiology* / Q000378:metabolism*; D008954:Models, Biological; D009422:Nervous System Diseases / Q000150:complications* / Q000378:metabolism*; D009994:Osmolar Concentration; D017483:Receptors, Vasopressin / Q000502:physiology; D012964:Sodium / Q000097:blood; D014667:Vasopressins / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000502:physiology; D014883:Water-Electrolyte Imbalance / Q000503:physiopathology
D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D014667:Vasopressins; D012964:Sodium