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.

• Authors: Kesia Palma-Rigo, Kristy L Jackson, Pamela J Davern, Thu-Phuc Nguyen-Huu, Jean-Luc Elghozi, Geoffrey A Head
• Journal: Journal of hypertension (J Hypertens) Vol. 29 Issue 11 Pg. 2156-66 (Nov 2011) ISSN: 1473-5598 [Electronic] England
• PMID: 21941207 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Losartan

Topics

• Animals
• Antihypertensive Agents (therapeutic use)
• Behavior, Animal
• Blood Pressure
• Heart Rate
• Humans
• Hypertension (metabolism, pathology)
• Losartan (therapeutic use)
• Male
• Mice
• Pressure
• Renin-Angiotensin System (physiology)
• Sympathetic Nervous System (physiology)
• Telemetry (methods)