Renin–angiotensin and sympathetic nervous system contribution to high blood pressure in Schlager mice

K Palma-Rigo, KL Jackson, PJ Davern… - Journal of …, 2011 - journals.lww.com
K Palma-Rigo, KL Jackson, PJ Davern, TP Nguyen-Huu, JL Elghozi, GA Head
Journal of hypertension, 2011journals.lww.com
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 …
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.
Lippincott Williams & Wilkins