Blood pressure and plasma renin activity responses to different strategies to inhibit the renin-angiotensin-aldosterone system during exercise

J Renin Angiotensin Aldosterone Syst. 2013 Mar;14(1):56-66. doi: 10.1177/1470320312454766. Epub 2012 Aug 2.

Abstract

Objective: The effect of two different strategies for renin-angiotensin-aldosterone system (RAAS) blockade; direct renin inhibition (DRI) versus angiotensin receptor blockade (ARB) on blood pressure (BP) and plasma renin activity (PRA) was compared during exercise.

Methods: Hypertensive adults were randomised to aliskiren (300 mg once daily, n=33) or valsartan (320 mg once daily, n=35). BP and PRA were measured during treadmill exercise (Bruce protocol), at baseline, end of treatment (eight weeks), and after treatment withdrawal (48 hours after last dose).

Results: After eight weeks treatment, Aliskiren inhibited PRA (>80%) at rest and during exercise, with inhibition remaining undiminished 48 hours after treatment withdrawal. In contrast, valsartan increased PRA at rest, and more-so during exercise (>400%). Angiotensin receptor blockade, as indicated by PRA increase, was reduced, 48 hours after valsartan treatment withdrawal, suggesting more sustained RAAS blockade with aliskiren. Despite divergent effects on PRA, similar exercise-induced changes in BP were seen. The primary outcome, the rise in systolic BP from rest to peak exercise (baseline to after treatment withdrawal) did not differ between treatments (p=0.25).

Conclusion: Measurement of PRA is a more sensitive index of RAAS blockade than the BP response during exercise. Furthermore, after treatment withdrawal, aliskiren provides more sustained RAAS inhibition than valsartan at rest and during exercise.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amides / administration & dosage
  • Amides / adverse effects
  • Amides / pharmacology
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Blood Pressure* / drug effects
  • Demography
  • Endpoint Determination
  • Exercise / physiology*
  • Female
  • Fumarates / administration & dosage
  • Fumarates / adverse effects
  • Fumarates / pharmacology
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Renin / blood*
  • Renin-Angiotensin System* / drug effects
  • Systole / drug effects
  • Tetrazoles / administration & dosage
  • Tetrazoles / adverse effects
  • Tetrazoles / pharmacology
  • Valine / administration & dosage
  • Valine / adverse effects
  • Valine / analogs & derivatives
  • Valine / pharmacology
  • Valsartan

Substances

  • Amides
  • Fumarates
  • Tetrazoles
  • Natriuretic Peptide, Brain
  • aliskiren
  • N,N-dimethylarginine
  • Valsartan
  • Arginine
  • Renin
  • Valine