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

Changes in fluid and electrolyte homeostasis may accompany and are likely to modify the clinical symptoms of alcohol-withdrawal reactions. It was of obvious theoretical and practical interest therefore to investigate the changes in the secretion of hormones, which regulate the fluid and electrolyte homeostasis (atrial natriuretic peptide, aldosterone and plasma renin activity) during alcohol withdrawal in chronic alcoholic patients. In a phase of severe withdrawal, there were increased plasma renin activity and aldosterone levels observed. In a phase of partial recovery, on the other hand, the elevated plasma renin activity and aldosterone levels were back to the normal range. In 60% of the patients, delirium tremens was gradually developing during the observation period. In these patients, an elevated level of atrial natriuretic peptide was observed at the time of hospital admission, i.e. days before the actual onset of delirium tremens. It is concluded that the 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 central nervous atrial natriuretic peptide, mice were rendered tolerant to and dependent on alcohol with an alcohol-liquid diet for 14 days. Five hours after withdrawal from alcohol, withdrawal hyperexcitability symptoms were analyzed. Intracerebroventricular (i.c.v.) injection of atrial natriuretic peptide attenuated, whereas that of an antiserum against atrial natriuretic peptide intensified the severity of handling-induced convulsions. N-methyl-D-aspartate induced behavioral seizures in a dose-dependent manner, whose effect was more intensive during the alcohol-withdrawal period than in alcohol-naive animals. I.c.v. injections of atrial natriuretic peptide dose-dependently inhibited, whereas that of antiserum against atrial natriuretic peptide potentiated the seizure-inducing effect of N-methyl-D-aspartate in alcohol-dependent mice. Although tentatively, it is concluded that peripheral secretion of atrial natriuretic peptide may be an indicator, whereas central nervous atrial natriuretic peptide a neuropeptide modulator of alcohol-withdrawal symptomatology.