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Renin-angiotensin and sympathetic nervous system contribution to high blood pressure in Schlager mice.
MedLine Citation:
PMID:  21941207     Owner:  NLM     Status:  Publisher    
OBJECTIVE: Schlager hypertensive (BPH/2J) mice have been suggested to have high blood pressure (BP) due to an overactive sympathetic nervous system (SNS), but the contribution of the renin-angiotensin system (RAS) is unclear. In the present study, we examined the cardiovascular effects of chronically blocking the RAS in BPH/2J mice. METHODS: Schlager normotensive (BPN/3J, n = 6) and BPH/2J mice (n = 8) received the angiotensin AT1A-receptor antagonist losartan (150 mg/kg per day) in drinking water for 2 weeks. Pre-implanted telemetry devices were used to record mean arterial pressure (MAP), heart rate (HR) and locomotor activity. RESULTS: MAP was reduced by losartan treatment in BPN/3J (-23 mmHg, P < 0.01) and in BPH/2J mice (-25 mmHg, P < 0.001), whereas HR was increased. Losartan had little effect on initial pressor responses to feeding or to stress, but did attenuate the sustained pressor response to cage-switch stress. During the active period, the hypotension to sympathetic blockade with pentolinium was greater in BPH/2J than BPN/3J (suggesting neurogenic hypertension), but was not affected by losartan. During the inactive period, a greater depressor response to pentolinium was observed in losartan-treated animals. CONCLUSION: The hypotensive actions of losartan suggest that although the RAS provides an important contribution to BP, it contributes little, if at all, to the hypertension-induced or the greater stress-induced pressor responses in Schlager mice. The effects of pentolinium suggest that the SNS is mainly responsible for hypertension in BPH/2J mice. However, the RAS inhibits sympathetic vasomotor tone during inactivity and prolongs sympathetic activation during periods of adverse stress, indicating an important sympatho-modulatory role.
Kesia Palma-Rigo; Kristy L Jackson; Pamela J Davern; Thu-Phuc Nguyen-Huu; Jean-Luc Elghozi; Geoffrey A Head
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-21
Journal Detail:
Title:  Journal of hypertension     Volume:  -     ISSN:  1473-5598     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
aNeuropharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia bINSERM U 970, Centre de Recherche Cardiovasculaire cUniversité Paris Descartes, Paris, France dDepartment of Pharmacology, Monash University, Clayton, Victoria, Australia.
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