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

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.

Keywords

Aliskiren valsartan exercise testing hypertension treatment withdrawal plasma renin activity antihypertensive therapy

Get full access to this article

View all access options for this article.

References

Franz

. Exercise hypertension: its measurement and evaluation. Herz 1987; 12: 99–109.

Moller

Grontved

Wedderkopp

. Cardiovascular disease risk factors and blood pressure response during exercise in healthy children and adolescents: the European Youth Heart Study. J Appl Physiol 2010; 109: 1125–1132.

Singh

Larson

Manolio

. Blood pressure response during treadmill testing as a risk factor for new-onset hypertension. The Framingham heart study. Circulation 1999; 99: 1831–1836.

Tanji

Champlin

Wong

. Blood pressure recovery curves after submaximal exercise. A predictor of hypertension at ten-year follow-up. Am J Hypertens 1989; 2: 135–138.

Kurl

Laukkanen

Rauramaa

. Systolic blood pressure response to exercise stress test and risk of stroke. Stroke 2001; 32: 2036–2041.

Mundal

Kjeldsen

Sandvik

. Exercise blood pressure predicts mortality from myocardial infarction. Hypertension 1996; 27: 324–329.

Ren

Hakki

Kotler

. Exercise systolic blood pressure: a powerful determinant of increased left ventricular mass in patients with hypertension. J Am Coll Cardiol 1985; 5: 1224–1231.

Aldigier

Huang

Dalmay

. Angiotensin-converting enzyme inhibition does not suppress plasma angiotensin II increase during exercise in humans. J Cardiovasc Pharmacol 1993; 21: 289–295.

Fallo

. Renin-angiotensin-aldosterone system and physical exercise. J Sports Med Phys Fitness 1993; 33: 306–312.

10.

Warner

Jr Metzger

Kitzman

. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. J Am Coll Cardiol 1999; 33: 1567–1572.

11.

Sullivan

Cervenka

O’Connor

. Fosenopril, an angiotensin-converting enzyme inhibitor, and propranolol: comparative effects at rest and exercise on blood pressure, hormonal variables, and plasma potassium in essential hypertension. Cardiovasc Drugs Ther 1989; 3: 57–62.

12.

Rangemark

Lind

Lindholm

. Lisinopril reduces postexercise albuminuria more effectively than atenolol in primary hypertension. Eur J Clin Pharmacol 1996; 49: 267–271.

13.

Little

Wesley-Farrington

Hoyle

. Effect of candesartan and verapamil on exercise tolerance in diastolic dysfunction. J Cardiovasc Pharmacol 2004; 43: 288–293.

14.

Duprez

Florea

Jones

. Beneficial effects of valsartan in asymptomatic individuals with vascular or cardiac abnormalities: the DETECTIV Pilot Study. J Am Coll Cardiol 2007; 50: 835–839.

15.

Czendlik

Sioufi

Preiswerk

. Pharmacokinetic and pharmacodynamic interaction of single doses of valsartan and atenolol. Eur J Clin Pharmacol 1997; 52: 451–459.

16.

Azizi

Webb

Nussberger

. Renin inhibition with aliskiren: where are we now, and where are we going? J Hypertens 2006; 24: 243–256.

17.

Prescott

Wright

Keefe

. Aliskiren, both as monotherapy and in combination with valsartan, reduces plasma aldosterone in patients with hypertension. J Hypertens 2010; 28: e383.

18.

Fisher

NDL

Danser

AHJ

Nussberger

. Renal and hormaonal responses to direct renin inhibition with aliskiren in healthy humans. Circulation 2008; 117: 3199–3205.

19.

Stevanovic

Price

Lansang

. Renin release in response to renin system blockade: Activation of the renin system in type 1 diabetes mellitus. JRAAS 2005; 6: 78–83.

20.

Gibbons

Balady

Bricker

. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation 2002; 106: 1883–1892.

21.

ESC Working Group on Exercise Physiology, Physiopathology and Electrocardiography. Guidelines for cardiac exercise testing. Eur Heart J 1993; 14: 969–988.

22.

Palatini

Jung

Shlyakhto

. Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study. J Hum Hypertens 2010; 24: 93–103.

23.

Gradman

Kad

. Renin inhibition in hypertension. J Am Coll Cardiol 2008; 51: 519–528.

24.

Ahlborg

Lundberg

. Exercise-induced changes in neuropeptide Y, noradrenaline and endothelin-1 levels in young people with type I diabetes. Clin Physiol 1996; 16: 645–655.

25.

Lim

Donnan

MacDonald

. Aldosterone to renin ratio as a determinant of exercise blood pressure response in hypertensive patients. J Hum Hypertens 2001; 15: 119–123.

26.

Shim

Park

. Exaggerated blood pressure response to exercise is associated with augmented rise of angiotensin II during exercise. J Am Coll Cardiol 2008; 52: 287–292.

27.

Sullivan

Dineen

Cervenka

. Effects of fosenopril, a once-daily angiotensin-converting enzyme inhibitor, on resting and exercise-induced changes of blood pressure, hormonal variables, and plasma potassium in essential hypertension. Am J Hypertens 1988; 1: 280S–283S.

28.

Bair

May

Prescott

. Association between baseline plasma renin activity and risk of cardiovascular events in coronary artery disease patients. J Clin Hypertens (Greenwich) 2009; 11: A88 (Abstract P-176).

29.

Masson

Solomon

Angelici

. Elevated plasma renin activity predicts adverse outcome in chronic heart failure, independently of pharmacologic therapy: data from the Valsartan Heart Failure Trial (Val-HeFT). J Card Fail 2010; 16: 964–970.

30.

Muhlestein

May

Bair

. Relation of elevated plasma renin activity at baseline to cardiac events in patients with angiographically proven coronary artery disease. Am J Cardiol 2010; 106: 764–769.

31.

Vergaro

Fontana

Poletti

. Plasma renin activity is an independent prognostic factor in chronic heart failure. Eur Heart J 2008; 29: 393 (Abstract 2493).

32.

Verma

Gupta

Holmes

. Plasma renin activity predicts cardiovascular mortality in the Heart Outcomes Prevention Evaluation (HOPE) study. Eur Heart J 2011; 32: 2135–2142.

33.

Gheorghiade

Albaghdadi

Zannad

. Rationale and design of the multicentre, randomized, double-blind, placebo-controlled Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT). Eur J Heart Fail 2011; 13: 100–106.

34.

Krum

Massie

Abraham

. Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study. Eur J Heart Fail 2011; 13: 107–114.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.10 MB