Renin–angiotensin and sympathetic nervous system contribution to high blood pressure in Schlager mice
Abstract
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 AT 1A-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.
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BPH/2J mice are a genetic model of lifelong hypertension and show some cardinal features of essential hypertension, including neurohumoral dysfunction, sympathetic activation, cardiac hypertrophy, and kidney atrophy.
“BPH/2J mice are a model of lifelong hypertension on a genetic basis and manifest some of the cardinal features of essential hypertension, i.e., neurohumoral dysfunction, sympathetic activation, cardiac hypertrophy, and kidney atrophy (58,59).”
From Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension (2016) · cites this paper as [59]
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- Authors
- Palma-Rigo, K., Jackson, K. L., Davern, P. J., Nguyen-Huu, T.-P., Elghozi, J.-L., & Head, G. A.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Inserm (FR)
- Corresponding author
- Head, Geoffrey A.
- Venue
- Journal of Hypertension
- Published
- 2011-11
- Volume
- 29
- Issue
- 11
- Pages
- 2156-2166
- ISSN
- 0263-6352 (ISSN-L)
- OpenAlex
- W2333243992
- Cited by
- 23
- References
- 47
- Citations by year
- 2024: 1 · 2023: 2 · 2021: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-08-BLAN-0175)
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- renin-angiotensin system, sympathetic nervous system, hypertension, losartan, neurogenic hypertension, pentolinium, sympathetic vasomotor tone, mean arterial pressure, heart rate, locomotor activity
- MeSH terms
- Animals, Antihypertensive Agents, Behavior, Animal, Blood Pressure, Heart Rate, Humans, Hypertension, Male, Pressure, Renin-Angiotensin System, Sympathetic Nervous System, Telemetry, Losartan, Mice
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