Skip to main content
SpringerLink
Log in

Cardiac remodeling and function following exercise and angiotensin II receptor antagonism

  • Short Communication
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

The purpose of this study was to test the impact of chronic exercise training combined with selective angiotensin II receptor (AT1) antagonism on systolic blood pressure (SBP) and the left-ventricular pressure–volume relationship in normotensive, non-infarcted rat hearts. Wistar rats (N = 19) were randomly assigned to either a sedentary control group (N = 8) or an exercise-trained group (N = 11). Losartan was administered to individually caged rats via the drinking water (10 mg/kg/d). Exercise training consisted of running on a motorized driven treadmill for 6 weeks at 30 m/min, 60 min/day, 5 days/week. Tail cuff SBP was measured weekly. Left ventricular performance was assessed in an ex vivo Langendorff isovolumic mode. One week of losartan treatment significantly reduced SBP in both groups by 13% relative to baseline (P < 0.05). SBP was lower in exercise-trained animals versus sedentary animals in the later weeks of the protocol (P < 0.05) Body weight was significantly lower in exercise-trained animals versus sedentary animals, but heart weight, heart to body weight ratio, atrial weight, and absolute left ventricular mass and length were similar between groups. The LV systolic pressure–volume relationship (PV) and systolic elastance were significantly greater in exercise-trained animals versus sedentary controls (P < 0.05). The left ventricular end-diastolic PV and diastolic stiffness were similar between exercise-trained and sedentary animals. These data suggest that chronic aerobic exercise training can improve the Starling response in the presence of AT1 receptor blockade without altering absolute cardiac size.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  • Abel ED, Litwin SE, Sweeney G (2008) Cardiac remodeling in obesity. Physiol Rev 88:389–419

    Article  PubMed  CAS  Google Scholar 

  • Azevedo LF, Brum PC, Mattos KC, Junqueira CM, Rondon MUMP, Barretto ACP, Negrão CE (2003) Effects of losartan combined with exercise training in spontaneously hypertensive rats Braz. J Med Biol Res 36(11):1595–1603

    CAS  Google Scholar 

  • Barauna VG, Magalhaes FC, Krieger JE, Oliveira EM (2008) AT1 receptor participates in the cardiac hypertrophy induced by resistance training in rats AJP. Regul Physiol 295(2):R381–R387

    CAS  Google Scholar 

  • Bevegard S, Holmgren A, Jonsson B (1963) Circulatory studies in well trained athletes at rest and during heavy exercise, with special reference to stroke volume and the influence of body position. Acta Physiol Scand 57:26–50

    Article  PubMed  CAS  Google Scholar 

  • Campbell DJ, Kladis A, Valentijn AJ (1995) Effects of losartan on angiotensin II blockade compared to converting enzyme inhibition angiotensin and bradykinin peptides and angiotensin-converting enzyme. J Cardiovasc Pharmacol 26:233–240

    Article  PubMed  CAS  Google Scholar 

  • Diffee GM, Seversen EA, Titus MM (2001) Exercise training increases the Ca(2+) sensitivity of tension in rat cardiac myocytes. J Appl Physiol 91(1):309–315

    PubMed  CAS  Google Scholar 

  • Fabiato A, Fabiato F (1975) Dependence of the contractile activation of skinned cardiac cells on the sarcomere length. Nature 256:54–56

    Article  PubMed  CAS  Google Scholar 

  • Hofmann PA, Fuchs F (1987) Effect of length and cross-bridge attachment on Ca2+ binding to cardiac troponin C. Am J Physiol 253:C90–C96

    PubMed  CAS  Google Scholar 

  • Jain M, Liao R, Ngoy S, Whittaker P, Apstein CS, Eberli FR (2000) Angiotensin II receptor blockade attenuates the deleterious effects of exercise training on post-MI ventricular remodelling in rats. Cardiovasc Res 46(1):66–72

    Article  PubMed  CAS  Google Scholar 

  • Kemi OJ, Høydal MA, Haram PM, Garnier A, Fortin D, Ventura-Clapier R, Ellingsen O (2007) Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan. Cardiovasc Res 76(1):91–99

    Article  PubMed  CAS  Google Scholar 

  • Kolwicz SC, MacDonnell SM, Renna BF, Reger PO, Seqqat R, Rafiq K, Kendrick ZV, Houser SR, Sabri A, Libonati JR (2009) Left ventricular remodeling with exercise in hypertension. Am J Physiol Heart Circ Physiol 297(4):H1361–H1368

    Article  PubMed  CAS  Google Scholar 

  • Libonati JR (2003) Exercise and diastolic function after myocardial infarction. Med Sci Sports Exerc 35(9):1471–1476

    Article  PubMed  Google Scholar 

  • Libonati JR (2011) Cardiac remodeling and exercise training in hypertension. Curr Hypertens Rev 7:20–28

    Article  Google Scholar 

  • Libonati JR, Eberli FR, Sesselberg HW, Apstein CS (1997) Effects of low-flow ischemia on the positive inotropic action of angiotensin II in isolated rabbit and rat hearts. Cardiovasc Res 33(1):71–81

    Article  PubMed  CAS  Google Scholar 

  • Libonati JR, Sabri A, Xiao C, Macdonnell SM, Renna BF (2011) Exercise training improves bad phosphorylation in hypertensive myocardium. J Appl Physiol. Sep 15. [Epub ahead of print]

  • MacDonnell SM, Kubo H, Crabbe DL, Renna BF, Reger PO, Mohara J, Smithwick LA, Koch WJ, Houser SR, Libonati JR (2005) Improved myocardial beta-adrenergic responsiveness and signaling with exercise training in hypertension. Circulation 111(25):3420–3428

    Article  PubMed  CAS  Google Scholar 

  • Malhotra R, Sadoshima J, Brosius FC 3rd, Izumo S (1999) Mechanical stretch and angiotensin II differentially upregulate the renin-angiotensin system in cardiac myocytes In vitro. Circ Res 85:137–146

    Article  PubMed  CAS  Google Scholar 

  • McGuire DK, Levine BD, Williamson JW, Snell PG, Blomqvist CG, Saltin B, Mitchell JH (2001) A 30-year follow-up of the Dallas Bedrest and Training Study: II. Effect of age on cardiovascular adaptation to exercise training. Circulation 104(12):1358–1366

    Article  PubMed  CAS  Google Scholar 

  • McMullen JR, Tetsuo S, Zhang L, Tarnavski O, Sherwood MC, Kang P, Izumo S (2003) Phosphoinositide 3-kinase(p110alpha) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy. Proc Natl Acad Sci USA 100(21):12355–12360

    Article  PubMed  CAS  Google Scholar 

  • Miyata S, Haneda T, Osaki J, Kikuchi K (1996) Renin-angiotensin system in stretch-induced hypertrophy of cultured neonatal rat heart cells. Eur J Pharmacol 307:81–88

    Article  PubMed  CAS  Google Scholar 

  • Moore RL, Palmer BM (1999) Exercise training and cellular adaptations of normal and diseased hearts. Exerc Sport Sci Rev 27:285–315

    Article  PubMed  CAS  Google Scholar 

  • Naylor LH, George K, O’Driscoll G, Green DJ (2008) The athlete’s heart: a contemporary appraisal of the ‘Morganroth hypothesis’. Sports Med, 38(1):69–90. Review

    Google Scholar 

  • Paradis P, Dali-Youcef N, Paradis FW, Thibault G, Nemer M (2000) Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling. Proc Natl Acad Sci USA 97:931–936

    Article  PubMed  CAS  Google Scholar 

  • Renna BF, Kubo H, MacDonnell SM, Crabbe DL, Reger PO, Houser SR, Libonati JR (2006) Enhanced acidotic myocardial Ca2+ responsiveness with training in hypertension. Med Sci Sports Exerc 38(5):847–855

    Article  PubMed  CAS  Google Scholar 

  • Renna BF, MacDonnell SM, Reger PO, Crabbe DL, Houser SR, Libonati JR (2007) Relative systolic dysfunction in female spontaneously hypertensive rat myocardium. J Appl Physiol 103(1):353–358

    Article  PubMed  Google Scholar 

  • Sadoshima J, Xu Y, Slayter HS, Izumo S (1993) Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75:977–984

    Article  PubMed  CAS  Google Scholar 

  • Tufescu A, Kanazawa M, Ishida A, Lu H, Sasaki Y, Ootaka T, Sato T, Kohzuki M (2008) Combination of exercise and losartan enhances renoprotective and peripheral effects in spontaneously type 2 diabetes mellitus rats with nephropathy. J Hypertens 26(2):312–321

    Article  PubMed  CAS  Google Scholar 

  • Wisløff U, Loennechen JP, Falck G, Beisvag V, Currie S, Smith G, Ellingsen O (2001) Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats. Cardiovasc Res 50(3):495–508

    Article  PubMed  Google Scholar 

  • Xu X, Wan W, Ji L, Lao S, Powers AS, Zhao W, Erikson JM, Zhang JQ (2008) Exercise training combined with angiotensin II receptor blockade limits post-infarct ventricular remodeling in rats. Cardiovasc Res 78(3):523–532

    Article  PubMed  CAS  Google Scholar 

  • Xu X, Zhao W, Wan W, Ji LL, Powers AS, Erikson JM, Zhang JQ (2010) Exercise training combined with angiotensin II receptor blockade reduces oxidative stress after myocardial infarction in rats. Exp Physiol 95(10):1008–1015

    Article  PubMed  CAS  Google Scholar 

  • Yasuda N, Miura S, Akazawa H, Tanaka T, Qin Y, Kiya Y, Imaizumi S, Fujino M, Ito K, Zou Y, Fukuhara S, Kunimoto S, Fukuzaki K, Sato T, Ge J, Mochizuki N, Nakaya H, Saku K, Komuro I (2008) Conformational switch of angiotensin II type 1 receptor underlying mechanical stress-induced activation. EMBO Rep 9:179–186

    Article  PubMed  CAS  Google Scholar 

  • Zou Y, Akazawa H, Qin Y, Sano M, Takano H, Minamino T, Makita N, Iwanaga K, Zhu W, Kudoh S, Toko H, Tamura K, Kihara M, Nagai T, Fukamizu A, Umemura S, Iiri T, Fujita T, Komuro I (2004) Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol 6:499–506

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biobehavioral and Health Sciences, School of Nursing, University of Pennsylvania, 135 Claire M. Fagin Hall, 418 Curie Boulevard, Philadelphia, PA, 19104-4217, USA

    Joseph R. Libonati

Authors
  1. Joseph R. Libonati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph R. Libonati.

Additional information

Communicated by Keith Phillip George.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Libonati, J.R. Cardiac remodeling and function following exercise and angiotensin II receptor antagonism. Eur J Appl Physiol 112, 3149–3154 (2012). https://doi.org/10.1007/s00421-011-2263-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-011-2263-y

Keywords

Search

Navigation