title: Effects of aldehyde dehydrogenase-2 genotype on cardiovascular and endocrine responses to alcohol in young Japanese subjects.
abstract: The present study was designed to investigate the effects of aldehyde dehydrogenase-2 (ALDH2) genotype on cardiovascular and endocrine responses to alcohol ingestion in young, healthy Japanese subjects. For this purpose, we monitored changes in the electrocardiogram (ECG), blood pressure (BP), finger blood flow (BF) and facial skin temperature (FST) during and after alcohol ingestion (0.4 ml/kg body weight). Spectral analyses of beat-to-beat variations of heart rate (HR), BP and BF were applied. Two major spectral components were examined at low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-10.4 Hz) bands for HR and BP variability (BPV). Significant effects for ALDH2 genotype were observed in HR variability (HRV) analysis; HF power of HRV was markedly depressed and the LF/HF ratio was significantly higher with alcohol in ALDH2-deficient (ND) subjects, while ALDH2-normal (NN) subjects did not display such changes. Analysis of BP variability showed increased LF and HF power after alcohol ingestion in the NN subjects, but there were no significant differences between genotypic groups. We also examined BF variability (BFV) in six major spectral components; power of the 0.8-2.2 Hz frequency band was significantly affected by genotype and higher power was observed in the ND subjects. Plasma concentrations of both epinephrine and norepinephrine increased after alcohol ingestion only in the ND subjects. Furthermore, plasma concentrations and urinary excretion of epinephrine, but not norepinephrine, were higher after alcohol ingestion in the ND than in the NN subjects. Blood acetaldehyde levels were about 10-fold higher in the ND than in the NN subjects although blood alcohol levels similarly increased in the ND and NN subjects. Our results also indicated that alcohol ingestion increased secretion of pituitary-adrenal hormones including ACTH, beta-endorphin and cortisol in the ND subjects. The present results along with previous studies suggest that alcohol-induced tachycardia in the ND subjects was probably mediated by acetaldehyde-induced rise in epinephrine secretion from the adrenal medulla and/or changes in the autonomic nervous system. Alcohol-induced relative predominance of cardiac sympathetic activity in the ND subjects might be ascribed partly to increased norepinephrine secretion from sympathetic nerve terminals. Effects of acetaldehyde on these cardiovascular and endocrine systems were discussed in terms of their effects on the central nervous system.
authors.affiliation: Central Laboratories for Key Technology, Kirin Brewery Co., Ltd., 1-13-5, Fukuura, Kanazawa, Yokohama, Kanagawa 236-0004, Japan. nfusae@kirin.co.jp
authors.forename: Fusae T
authors.initials: FT
authors.lastname: Nishimura
authors.forename: Tatsushige
authors.initials: T
authors.lastname: Fukunaga
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kajiura
authors.forename: Katsumi
authors.initials: K
authors.lastname: Umeno
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Takakura
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Ono
authors.forename: Hisao
authors.initials: H
authors.lastname: Nishijo
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D002319:Cardiovascular System / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D004703:Endocrine System / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D012677:Sensation / Q000187:drug effects / Q000235:genetics
chemical_list: D002395:Catecholamines; D000431:Ethanol; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial