Skip to main content
SpringerLink
Log in

Fosinopril improves the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rats

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

This study investigated the effects of fosinopril on the electrophysiological characteristics of the left ventricular hypertrophic myocardium in spontaneously hypertensive rats (SHRs). Twenty-four 10-week-old male SHRs were divided into fosinopril and non-fosinopril groups (n = 12 each). Twelve 10-week-old Wistar–Kyoto rats were used a control group. Left ventricular mass index and ventricular fibrillation threshold (VFT) were measured after 8 weeks of fosinopril or saline treatment. L-type calcium current (I CaL), sodium current (I Na), and transient outward potassium current (I to) were measured in left ventricular myocytes after 8 weeks of fosinopril or saline treatment using the whole-cell patch-clamp technique. VFT was higher in the fosinopril group than in the non-fosinopril group (17.5 ± 1.2 mA vs. 15.6 ± 1.1 mA, P < 0.01). The density of I CaL was lower in the fosinopril group than in the non-fosinopril group (−7.17 ± 0.13 pA/pF vs. −7.87 ± 0.13 pA/pF, P < 0.05). The density of I to was higher in the fosinopril group than in the non-fosinopril group (14.46 ± 0.28 pA/pF vs. 12.66 ± 0.25 pA/pF, P < 0.05). I to was positively correlated with VFT (r = 0.90, P < 0.001) and was found to be associated independently with VFT (P < 0.001). Fosinopril improves the electrophysiological characteristics of the left ventricular hypertrophic myocardium in SHRs.

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
Fig. 3

Similar content being viewed by others

References

  • Ahmmed GU, Dong PH, Song G, Ball NA, Xu Y, Walsh RA, Chiamvimonvat N (2000) Changes in Ca(2+) cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure. Circ Res 86(5):558–570

    Article  PubMed  CAS  Google Scholar 

  • Cerbai E, Barbieri M, Mugelli A (1994) Characterization of the hyperpolarization-activated current, I(f), in ventricular myocytes isolated from hypertensive rats. J Physiol 481(Pt 3):585–591

    PubMed  CAS  PubMed Central  Google Scholar 

  • Cerbai E, Crucitti A, Sartiani L, De Paoli P, Pino R, Rodriguez ML, Gensini G, Mugelli A (2000) Long-term treatment of spontaneously hypertensive rats with losartan and electrophysiological remodeling of cardiac myocytes. Cardiovasc Res 45(2):388–396

    Article  PubMed  CAS  Google Scholar 

  • Chevalier B, Heudes D, Heymes C, Basset A, Dakhli T, Bansard Y, Jouquey S, Hamon G, Bruneval P, Swynghedauw B (1995) Trandolapril decreases prevalence of ventricular ectopic activity in middle-aged SHR. Circulation 92(7):1947–1953

    Article  PubMed  CAS  Google Scholar 

  • Cutler MJ, Jeyaraj D, Rosenbaum DS (2011) Cardiac electrical remodeling in health and disease. Trends Pharmacol Sci 32(3):174–180

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Drechsler C, Meinitzer A, Pilz S, Krane V, Tomaschitz A, Ritz E, März W, Wanner C (2011) Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients. Eur J Heart Fail 13(8):852–859

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Galatius-Jensen S, Wroblewski H, Emmeluth C, Bie P, Haunsø S, Kastrup J (1996) Plasma endothelin in congestive heart failure: effect of the ACE inhibitor, fosinopril. Cardiovasc Res 32(6):1148–1154

    Article  PubMed  CAS  Google Scholar 

  • Gómez AM, Valdivia HH, Cheng H, Lederer MR, Santana LF, Cannell MB, McCune SA, Altschuld RA, Lederer WJ (1997) Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science 276(5313):800–806

    Article  PubMed  Google Scholar 

  • He BX, Yu GL, Liang XQ (2001) Effects of lorsartan, fosinopril on myocardial fibrosis, angiotensin II and cardiac remolding in hypertensive rats. Hunan Yi Ke Da Xue Xue Bao 26(2):118–120

    PubMed  CAS  Google Scholar 

  • Isenberg G, Klockner U (1982) Calcium tolerant ventricular myocytes prepared by preincubation in a “KB medium”. Pflugers Arch 395(1):6–18

    Article  PubMed  CAS  Google Scholar 

  • Kääb S, Nuss HB, Chiamvimonvat N, O’Rourke B, Pak PH, Kass DA, Marban E, Tomaselli GF (1996) Ionic mechanism of action potential prolongation in ventricular myocytes from dogs with pacing-induced heart failure. Circ Res 78(2):262–273

    Article  PubMed  Google Scholar 

  • Kurokawa S, Niwano S, Niwano H, Ishikawa S, Kishihara J, Aoyama Y, Kosukegawa T, Masaki Y, Izumi T (2011) Progression of ventricular remodeling and arrhythmia in the primary hyperoxidative state of glutathione-depleted rats. Circ J 75(6):1386–1393

    Article  PubMed  CAS  Google Scholar 

  • Naggar I, Lazar J, Kamran H, Orman R, Stewart M (2014) Relation of autonomic and cardiac abnormalities to ventricular fibrillation in a rat model of epilepsy. Epilepsy Res 108(1):44–56

    Article  PubMed  Google Scholar 

  • Okin PM, Bang CN, Wachtell K, Hille DA, Kjeldsen SE, Dahlöf B, Devereux RB (2013) Relationship of sudden cardiac death to new-onset atrial fibrillation in hypertensive patients with left ventricular hypertrophy. Circ Arrhythm Electrophysiol 6(2):243–251

    Article  PubMed  CAS  Google Scholar 

  • Pahor M, Bernabei R, Sgadari A, Gambassi G Jr, Lo Giudice P, Pacifici L, Ramacci MT, Lagrasta C, Olivetti G, Carbonin P (1991) Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats. Hypertension 18(2):148–157

    Article  PubMed  CAS  Google Scholar 

  • Panikkath R, Reinier K, Uy-Evanado A, Teodorescu C, Gunson K, Jui J, Chugh SS (2013) Electrocardiographic predictors of sudden cardiac death in patients with left ventricular hypertrophy. Ann Noninvasive Electrocardiol 18(3):225–229

    Article  PubMed  PubMed Central  Google Scholar 

  • Raasch W, Bartels T, Schwartz C, Häuser W, Rütten H, Dominiak P (2002) Regression of ventricular and vascular hypertrophy: are there differences between structurally different angiotensin-converting enzyme inhibitors? J Hypertens 20(12):2495–2504

    Article  PubMed  CAS  Google Scholar 

  • Sah R, Ramirez RJ, Oudit GY, Gidrewicz D, Trivieri MG, Zobel C, Backx PH (2003) Regulation of cardiac excitation-contraction coupling by action potential repolarization: role of the transient outward potassium current (I(to)). J Physiol 546(Pt 1):5–18

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Shorofsky SR, Aggarwal R, Corretti M, Baffa JM, Strum JM, Al-Seikhan BA, Kobayashi YM, Jones LR, Wier WG, Balke CW (1999) Cellular mechanisms of altered contractility in the hypertrophied heart: big hearts, big sparks. Circ Res 84(4):424–434

    Article  PubMed  CAS  Google Scholar 

  • Tomaselli GF (2010) Oxidant stress derails the cardiac connexon connection. J Clin Invest 120(1):87–89

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Tomaselli GF, Beuckelmann DJ, Calkins HG, Berger RD, Kessler PD, Lawrence JH, Kass D, Feldman AM, Marban E (1994) Sudden cardiac death in heart failure. The role of abnormal repolarization. Circulation 90(5):2534–2539

    Article  PubMed  CAS  Google Scholar 

  • Tozakidou M, Goltz D, Hagenström T, Budack MK, Vitzthum H, Szlachta K, Bähring R, Ehmke H (2010) Molecular and functional remodeling of I(to) by angiotensin II in the mouse left ventricle. J Mol Cell Cardiol 48(1):140–151

    Article  PubMed  CAS  Google Scholar 

  • Winter J, Brack KE, Coote JH, Ng GA (2014) Cardiac contractility modulation increases action potential duration dispersion and decreases ventricular fibrillation threshold via β1-adrenoceptor activation in the crystalloid perfused normal rabbit heart. Int J Cardiol 172(1):144–154

    Article  PubMed  PubMed Central  Google Scholar 

  • Yokoshiki H, Kohya T, Tomita F, Tohse N, Nakaya H, Kanno M, Kitabatake A (1997) Restoration of action potential duration and transient outward current by regression of left ventricular hypertrophy. J Mol Cell Cardiol 29(5):1331–1339

    Article  PubMed  CAS  Google Scholar 

  • Yu G, Liang X, Xie X, Yang T, Sun M, Zhao S (2002) Apoptosis, myocardial fibrosis and angiotensin II in the left ventricle of hypertensive rats treated with fosinopril or losartan. Chin Med J (Engl) 115(9):1287–1291

    CAS  Google Scholar 

  • Zhi-Bin H, Chang F, Mao-Huan L, Gui-Yi Y, Shu-Xian Z, Wei W. Effect of fosinopril on the transient outward potassium current of hypertrophied left ventricular myocardium in the spontaneously hypertensive rat. Naunyn Schmiedebergs Arch Pharmacol. 2014 Jan 19. [Epub ahead of print]

Download references

Acknowledgments

This study was supported by the Guangdong Province Science and Technology Project Plan and Social Development of China (No. 2010B031600060).

Conflicts of interest

None declared.

Author information

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Zhi-Bin Huang

  2. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangzhou, 510080, China

    Chun-Yu Deng

  3. Department of Cardiology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Mao-Huan Lin & Gui-Yi Yuan

  4. Department of Cardiology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China

    Wei Wu

Authors
  1. Zhi-Bin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chun-Yu Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mao-Huan Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gui-Yi Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Wu.

Additional information

Zhi-Bin Huang and Chun-Yu Deng contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, ZB., Deng, CY., Lin, MH. et al. Fosinopril improves the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rats. Naunyn-Schmiedeberg's Arch Pharmacol 387, 1037–1044 (2014). https://doi.org/10.1007/s00210-014-1024-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-014-1024-y

Keywords

Search

Navigation