Document Detail

Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat.
MedLine Citation:
PMID:  12915399     Owner:  NLM     Status:  MEDLINE    
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.
Kazushige Tachikawa; Hisashi Yokoi; Hiroshi Nagasaki; Hiroshi Arima; Takashi Murase; Yoshihisa Sugimura; Yoshitaka Miura; Masumi Hirabayashi; Yutaka Oiso
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-08-12
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  285     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-11-10     Completed Date:  2004-01-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1161-6     Citation Subset:  IM    
Department of of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
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MeSH Terms
Adaptation, Physiological*
Animals, Genetically Modified
Arginine Vasopressin / blood,  metabolism*,  pharmacology
Blood Pressure / drug effects
Carotid Artery Diseases / blood,  metabolism,  physiopathology*
Hemorrhage / blood,  metabolism,  physiopathology*
Hemostasis / drug effects
Piperidines / pharmacology*
Quinolones / pharmacology*
Rats / genetics
Rats, Sprague-Dawley
Receptors, Vasopressin / antagonists & inhibitors,  metabolism*
Reg. No./Substance:
0/Piperidines; 0/Quinolones; 0/Receptors, Vasopressin; 113-79-1/Arginine Vasopressin; 131631-89-5/OPC 21268

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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