title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Neuropharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Kesia
authors.initials: K
authors.lastname: Palma-Rigo
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Jackson
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Davern
authors.forename: Thu-Phuc
authors.initials: TP
authors.lastname: Nguyen-Huu
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Elghozi
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Head
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001522:Behavior, Animal; D001794:Blood Pressure; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D051379:Mice; D011312:Pressure; D012084:Renin-Angiotensin System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013686:Telemetry / Q000379:methods
chemical_list: D000959:Antihypertensive Agents; D019808:Losartan