The role of atrial natriuretic peptide in alcohol withdrawal: a peripheralindicator and central modulator?

Changes in fluid and electrolyte homeostasis may accompany and are likely t o modify the clinical symptoms of alcohol-withdrawal reactions. It was of o bvious theoretical and practical interest therefore to investigate the chan ges in the secretion of hormones, which regulate the fluid and electrolyte homeostasis (atrial natriuretic peptide, aldosterone and plasma renin activ ity) during alcohol withdrawal in chronic alcoholic patients. In a phase of seven withdrawal, there were increased plasma renin activity and aldostero ne levels observed. In a phase of partial recovery, on the other hand, the elevated plasma renin activity and aldosterone levels were back to the norm al range. In 60% of the: patients, delirium tremens was gradually developin g during the observation period. In these patients, an elevated level of at rial natriuretic peptide was observed at the time of hospital admission, i. e. days before the actual onset of delirium tremens. It is concluded that t he disturbed volume homeostasis and the consequently altered plasma atrial natriuretic peptide secretion might be associated with, and therefore used as an indicator of the onset of delirium tremens. To study the role of cent ral nervous atrial natriuretic peptide, mice were rendered tolerant to and dependent on alcohol with an alcohol-liquid diet for 14 days. Five hours af ter withdrawal from alcohol, withdrawal hyperexcitability symptoms were ana lyzed. Intracerebroventricular (i.c.v.) injection of atrial natriuretic pep tide attenuated, whereas that of an antiserum against atrial natriuretic pe ptide intensified the severity of handling-induced convulsions. N-methyl-D- aspartate induced behavioral seizures in a dose-dependent manner, whose eff ect was more intensive during the alcohol-withdrawal period than in alcohol -naive animals. I.c.v. injections of atrial natriuretic peptide dose-depend ently inhibited, whereas that of antiserum against atrial natriuretic pepti de potentiated the seizure-inducing effect of N-methyl-D-aspartate in alcoh ol-dependent mice. Although tentatively, it is concluded that peripheral se cretion of atrial natriuretic peptide may be an indicator, whereas central nervous atrial natriuretic peptide a neuropeptide modulator of alcohol-with drawal symptomatology. (C) 2000 Elsevier Science B.V. All rights reserved.