title: The ethanol metabolite acetaldehyde induces water and salt intake via two distinct pathways in the central nervous system of rats.
abstract: The sensation of thirst experienced after heavy alcohol drinking is widely regarded as a consequence of ethanol (EtOH)-induced diuresis, but EtOH in high doses actually induces anti-diuresis. The present study was designed to investigate the introduction mechanism of water and salt intake after heavy alcohol drinking, focusing on action of acetaldehyde, a metabolite of EtOH and a toxic substance, using rats. The aldehyde dehydrogenase (ALDH) inhibitor cyanamide was used to mimic the effect of prolonged acetaldehyde exposure because acetaldehyde is quickly degraded by ALDH. Systemic administration of a high-dose of EtOH at 2.5 g/kg induced water and salt intake with anti-diuresis. Cyanamide enhanced the fluid intake following EtOH and acetaldehyde administration. Systemic administration of acetaldehyde with cyanamide suppressed blood pressure and increased plasma renin activity. Blockade of central angiotensin receptor AT1R suppressed the acetaldehyde-induced fluid intake and c-Fos expression in the circumventricular organs (CVOs), which form part of dipsogenic mechanism in the brain. In addition, central administration of acetaldehyde together with cyanamide selectively induced water but not salt intake without changes in blood pressure. In electrophysiological recordings from slice preparations, acetaldehyde specifically excited angiotensin-sensitive neurons in the CVO. These results suggest that acetaldehyde evokes the thirst sensation following heavy alcohol drinking, by two distinct and previously unsuspected mechanisms, independent of diuresis. First acetaldehyde indirectly activates AT1R in the dipsogenic centers via the peripheral renin-angiotensin system following the depressor response and induces both water and salt intake. Secondly acetaldehyde directly activates neurons in the dipsogenic centers and induces only water intake.
authors: Division of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita, Kitakyushu 803-8580, Japan; Division of Special Needs and Geriatric Dentistry, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita, Kitakyushu 803-8580, Japan.
authors: Izumi
authors: I
authors: Ujihara
authors: Division of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita, Kitakyushu 803-8580, Japan.
authors: Suzuro
authors: S
authors: Hitomi
authors: Division of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita, Kitakyushu 803-8580, Japan.
authors: Kentaro
authors: K
authors: Ono
authors: Division of Special Needs and Geriatric Dentistry, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita, Kitakyushu 803-8580, Japan.
authors: Yasuaki
authors: Y
authors: Kakinoki
authors: Department of Physiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishi, Kitakyushu 807-8555, Japan.
authors: Hirofumi
authors: H
authors: Hashimoto
authors: Department of Physiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishi, Kitakyushu 807-8555, Japan.
authors: Yoichi
authors: Y
authors: Ueta
authors: Division of Physiology, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita, Kitakyushu 803-8580, Japan. Electronic address: ine@kyu-dent.ac.jp.
authors: Kiyotoshi
authors: K
authors: Inenaga
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000503:physiopathology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D066280:Circumventricular Organs / Q000187:drug effects / Q000378:metabolism; D003484:Cyanamide / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D004326:Drinking / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D055647:Rats, Transgenic; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012083:Renin / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013894:Thirst / Q000187:drug effects* / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D002491:Central Nervous System Agents; D016760:Proto-Oncogene Proteins c-fos; D044140:Receptor, Angiotensin, Type 1; D017673:Sodium Chloride, Dietary; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000431:Ethanol; D003484:Cyanamide; D012083:Renin; D000079:Acetaldehyde
keywords: Acetaldehyde; Angiotensin II; Ethanol; Thirst