title: Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat.
abstract: Although arginine vasopressin (AVP), an antidiuretic hormone, has been widely acknowledged to play an important role in cardiovascular regulation via V1a receptors (V1aR), its precise significance remains unclear. In this study, we investigated the effects of long-standing high plasma AVP status on cardiovascular regulation in the AVP-overexpressing transgenic (Tg) rat. Adult male homozygous Tg rats were compared with age-matched normal Sprague-Dawley rats as controls. There were no significant differences in mean arterial blood pressure (BP; MABP) or heart rate between Tg and control rats in the basal state. Subcutaneous injection of AVP significantly increased MABP in controls but did not cause any apparent increase in MABP in Tg rats. BP recovery from hemorrhage-induced hypotension was significantly delayed in Tg compared with control rats. Pretreatment with a selective V1aR antagonist, OPC-21268, which is thought to restore the downregulation of V1aR, markedly improved both of these impaired responses. Northern blot analysis confirmed that decreased expression of V1aR mRNA and pretreatment with V1aR antagonist significantly restored the downregulation of V1aR mRNA. These results suggest that the Tg rat has decreased sensitivity to the hypertensive effect of AVP due to downregulation of V1aR, which may function as an adaptive mechanism to maintain normal BP against chronic hypervasopressinemia. In addition, impaired restoration of BP after hemorrhage-induced hypotension in Tg rats supports a physiological role of AVP in cardiovascular regulation.
authors.affiliation: Department of of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Tachikawa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yokoi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
authors.forename: Takashi
authors.initials: T
authors.lastname: Murase
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miura
authors.forename: Masumi
authors.initials: M
authors.lastname: Hirabayashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D030801:Animals, Genetically Modified; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D006470:Hemorrhage / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D006487:Hemostasis / Q000187:drug effects; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats / Q000235:genetics; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D010880:Piperidines; D015363:Quinolones; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C068644:OPC 21268