title: Effect of angiotensin AT1 receptor blockade on sympathetic responses to handgrip in healthy men.
abstract: BACKGROUND
  To determine whether angiotensin II (ANG II) contributes to the reflex skeletal muscle sympathoexcitation elicited by isometric and isotonic exercise, we tested the hypothesis that angiotensin AT(1) receptor blockade (ARB) would attenuate reflex sympathoneural responses to handgrip (HG) and to post-handgrip ischemia (PHGI).
  
  
  METHODS
  Seventeen healthy men were studied before and 1 week after random double-blind crossover allocation to oral losartan (100 mg daily) and placebo. Heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded at rest, and during 2 min bouts of isotonic HG at 50% maximum voluntary contraction (MVC) and isometric HG at 30% MVC, performed randomly, each followed by 2 min of PHGI.
  
  
  RESULTS
  At rest, losartan doubled plasma renin (P = 0.01) and ANG II (P = 0.03) concentrations, and lowered BP (P < 0.01) yet had no effect on MSNA burst frequency or incidence. HR trended higher (P = 0.060). Losartan's hypotensive effect persisted throughout each exercise bout (P < 0.045). MSNA and HR responses to isotonic exercise and postexercise ischemia were not affected by losartan. Isometric exercise and postexercise ischemia increased MSNA on both sessions (all P < 0.01). Losartan augmented the HR response (P ≤ 0.03), and after losartan MSNA burst frequency (P < 0.01) and incidence (P < 0.04) were significantly higher at all time points, but the magnitude of the MSNA response to isometric exercise and postexercise ischemia was unchanged.
  
  
  CONCLUSIONS
  In healthy men, short-term ARB does not attenuate reflex sympathoneural responses to HG or PHGI.
authors.affiliation: University Health Network, Mount Sinai Hospital, Division of Cardiology, Department of Medicine, University of Toronto, Ontario, Canada. mcgowanc@uwindsor.ca
authors.forename: Cheri L
authors.initials: CL
authors.lastname: McGowan
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Notarius
authors.forename: Andrew
authors.initials: A
authors.lastname: McReynolds
authors.forename: Beverley L
authors.initials: BL
authors.lastname: Morris
authors.forename: Derek S
authors.initials: DS
authors.lastname: Kimmerly
authors.forename: Peter E
authors.initials: PE
authors.lastname: Picton
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003080:Cold Temperature; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation; D012018:Reflex; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan