Skip to main content

Advertisement

SpringerLink
Log in

Effects of magnesium supplementation on electrophysiological remodeling of cardiac myocytes in L-NAME induced hypertensive rats

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

Hypertension is one of the major risk factors of cardiac hypertrophy and magnesium deficiency is suggested to be a contributing factor in the progression of this complication. In this study, we aimed to investigate the relationship between intracellular free Mg2+ levels and electrophysiological changes developed in the myocardium of L-NAME induced hypertensive rats. Hypertension was induced by administration of 40 mg/kg of L-NAME for 6 weeks, while magnesium treated rats fed with a diet supplemented with 1 g/kg of MgO for the same period. L-NAME administration for 6 weeks elicited a significant increase in blood pressure which was corrected with MgO treatment; thereby cardiac hypertrophy developing secondary to hypertension was prevented. Cytosolic free magnesium levels of ventricular myocytes were significantly decreased with hypertension and magnesium administration restored these changes. Hypertension significantly decreased the fractional shortening with slowing of shortening kinetics in left ventricular myocytes whereas magnesium treatment was capable of restoring hypertension-induced contractile dysfunction. Long-term magnesium treatment significantly restored the hypertension-induced prolongation in action potentials of ventricular myocytes and suppressed Ito and Iss currents. In contrast, hypertension dependent decrement in intracellular Mg2+ level did not cause a significant change in L-type Ca2+ currents, SR Ca2+ content and NCX activity. Nevertheless, hypertension mediated increase in superoxide anion, hydrogen peroxide and protein oxidation mitigated with magnesium treatment. In conclusion, magnesium administration improves mechanical abnormalities observed in hypertensive rat ventricular myocytes due to reduced oxidative stress. It is likely that, changes in intracellular magnesium balance may contribute to the pathophysiology of chronic heart diseases.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Almulla HA, Bush PG, Steele MG, Flatman PW, Ellis D (2006) Sodium-dependent recovery of ionised magnesium concentration following magnesium load in rat heart myocytes. Pflugers Arch 451:657–667

    Article  CAS  Google Scholar 

  • Altura BM, Altura BT (1985) New perspectives on the role of magnesium in the pathophysiology of the cardiovascular system. I. Clinical aspects. Magnesium 4:226–244

    CAS  Google Scholar 

  • Altura BM, Altura BT (1995) Magnesium and cardiovascular biology: an important link between cardiovascular risk factors and atherogenesis. Cell Mol Biol Res 41:347–359

    CAS  Google Scholar 

  • Aslan M, Canatan D (2008) Modulation of redox pathways in neutrophils from sickle cell disease patients. Exp Hematol 36:1535–1544

    Article  CAS  Google Scholar 

  • Aydemir M, Ozturk N, Dogan S, Aslan M, Olgar Y, Ozdemir S (2012) Sodium tungstate administration ameliorated diabetes-induced electrical and contractile remodeling of rat heart without normalization of hyperglycemia. Biol Trace Elem Res 148:216–223

    Article  CAS  Google Scholar 

  • Bara M, Guiet-Bara A (1984) Potassium, magnesium and membranes. Review of present status and new findings. Magnesium 3:215–225

    CAS  Google Scholar 

  • Brooksby P, Levi AJ, Jones JV (1993) The electrophysiological characteristics of hypertrophied ventricular myocytes from the spontaneously hypertensive rat. J Hypertens 11:611–622

    Article  CAS  Google Scholar 

  • Chan V, Fenning A, Levick SP, Loch D, Chunduri P, Iyer A, Teo YL, Hoey A, Wilson K, Burstow D, Brown L (2011) Cardiovascular changes during maturation and ageing in male and female spontaneously hypertensive rats. J Cardiovasc Pharmacol 57:469–478

    Article  CAS  Google Scholar 

  • Chen-Izu Y, Chen L, Banyasz T, McCulle SL, Norton B, Scharf SM, Agarwal A, Patwardhan A, Izu LT, Balke CW (2007) Hypertension-induced remodeling of cardiac excitation-contraction coupling in ventricular myocytes occurs prior to hypertrophy development. Am J Physiol Heart Circ Physiol 293:14

    Google Scholar 

  • Chouabe C, Ricci E, Kurdi M, Legrand C, Bricca G, Bonvallet R (2009) Evaluation of remodeling in left and right ventricular myocytes from heterozygous (mRen2)27 transgenic rats. Gen Physiol Biophys 28:24–38

    Article  CAS  Google Scholar 

  • De Artinano AA, Gonzalez VL (1999) Endothelial dysfunction and hypertensive vasoconstriction. Pharmacol Res 40:113–124

    Article  Google Scholar 

  • DeLano FA, Parks DA, Ruedi JM, Babior BM, Schmid-Schonbein GW (2006) Microvascular display of xanthine oxidase and NADPH oxidase in the spontaneously hypertensive rat. Microcirculation 13:551–566

    Article  CAS  Google Scholar 

  • Doggrell SA, Nand V, Henderson CJ (1999) The effects of lignocaine and tetrodotoxin on the action potentials and contractions of left ventricles from normo- and hypertensive rats. Gen Pharmacol 32:429–437

    Article  CAS  Google Scholar 

  • Fatholahi M, LaNoue K, Romani A, Scarpa A (2000) Relationship between total and free cellular Mg(2+) during metabolic stimulation of rat cardiac myocytes and perfused hearts. Arch Biochem Biophys 374:395–401

    Article  CAS  Google Scholar 

  • Gibbons GH (1997) Endothelial function as a determinant of vascular function and structure: a new therapeutic target. Am J Cardiol 79:3–8

    Article  CAS  Google Scholar 

  • Griffiths EJ (2000) Calcium handling and cell contraction in rat cardiomyocytes depleted of intracellular magnesium. Cardiovasc Res 47:116–123

    Article  CAS  Google Scholar 

  • Grubbs RD, Maguire ME (1987) Magnesium as a regulatory cation: criteria and evaluation. Magnesium 6:113–127

    CAS  Google Scholar 

  • Gupta RK, Moore RD (1980) 31P NMR studies of intracellular free Mg2+ in intact frog skeletal muscle. J Biol Chem 255:3987–3993

    CAS  Google Scholar 

  • Gupta RK, Benovic JL, Rose ZB (1978) Magnetic resonance studies of the binding of ATP and cations to human hemoglobin. J Biol Chem 253:6165–6171

    CAS  Google Scholar 

  • Gusev K, Niggli E (2008) Modulation of the local SR Ca2+ release by intracellular Mg2+ in cardiac myocytes. J Gen Physiol 132:721–730

    Article  CAS  Google Scholar 

  • Ishiguro S, Matsuyama T, Sakaguchi H, Nishio A (1997) Ex vivo study of the increased sensitivity to NO of endothelium-denuded thoracic aortas isolated from dietary magnesium-deficient rats. Magnes Res 10:21–31

    CAS  Google Scholar 

  • Keung EC (1989) Calcium current is increased in isolated adult myocytes from hypertrophied rat myocardium. Circ Res 64:753–763

    Article  CAS  Google Scholar 

  • Kharb S, Singh V (2000) Magnesium deficiency potentiates free radical production associated with myocardial infarction. J Assoc Physicians India 48:484–485

    CAS  Google Scholar 

  • Kirschenlohr HL, Metcalfe JC, Morris PG, Rodrigo GC, Smith GA (1988) Ca2+ transient, Mg2+, and pH measurements in the cardiac cycle by 19F NMR. Proc Natl Acad Sci U S A 85:9017–9021

    Article  CAS  Google Scholar 

  • Kiyosue T (2002) Removal of intracellular Mg(2+) activates cardiac Na(+)/Ca(2+) exchanger. Cardiovasc Res Feb 1;53(2):290–1.

  • Kramer JH, Misik V, Weglicki WB (1994) Magnesium-deficiency potentiates free radical production associated with postischemic injury to rat hearts: vitamin E affords protection. Free Radic Biol Med 16:713–723

    Article  CAS  Google Scholar 

  • Lacy F, Gough DA, Schmid-Schonbein GW (1998) Role of xanthine oxidase in hydrogen peroxide production. Free Radic Biol Med 25:720–727

    Article  CAS  Google Scholar 

  • Laurant P, Touyz RM, Schiffrin EL (1997) Effect of magnesium on vascular tone and reactivity in pressurized mesenteric resistance arteries from spontaneously hypertensive rats. Can J Physiol Pharmacol 75:293–300

    Article  CAS  Google Scholar 

  • Li X, Jiang W (2000) Electrical remodeling of membrane ionic channels of hypertrophied ventricular myocytes from spontaneously hypertensive rats. Chin Med J 113:584–587

    CAS  Google Scholar 

  • Li L, Desantiago J, Chu G, Kranias EG, Bers DM (2000) Phosphorylation of phospholamban and troponin I in beta-adrenergic-induced acceleration of cardiac relaxation. Am J Physiol Heart Circ Physiol 278:H769–H779

    CAS  Google Scholar 

  • Li SY, Golden KL, Jiang Y, Wang GJ, Privratsky JR, Zhang X, Eason AR, Culver B, Ren J (2005) Inhibition of sarco(endo)plasmic reticulum Ca2 + −ATPase differentially regulates contractile function in cardiac myocytes from normotensive and spontaneously hypertensive rats: role of Ca2+ regulatory proteins. Cell Biochem Biophys 42:1–12

    Article  Google Scholar 

  • Liao F, Folsom AR, Brancati FL (1998) Is low magnesium concentration a risk factor for coronary heart disease? The atherosclerosis risk in communities (ARIC) study. Am Heart J 136:480–490

    Article  CAS  Google Scholar 

  • Luo J, Xuan YT, Gu Y, Prabhu SD (2006) Prolonged oxidative stress inverts the cardiac force-frequency relation: role of altered calcium handling and myofilament calcium responsiveness. J Mol Cell Cardiol 40:64–75

    Article  CAS  Google Scholar 

  • Mahboob T, Mumtaz M, Haleem MA (1996) Electrolyte content of serum, erythrocyte, kidney and heart tissue in salt induced hypertensive rats. Life Sci 59:731–737

    Article  CAS  Google Scholar 

  • Manju L, Nair RR (2006) Magnesium deficiency augments myocardial response to reactive oxygen species. Can J Physiol Pharmacol 84:617–624

    Article  CAS  Google Scholar 

  • Mertens MJ, Mathy MJ, Pfaffendorf M, van Zwieten PA (1992) Depressed inotropic response to beta-adrenoceptor agonists in the presence of advanced cardiac hypertrophy in hearts from rats with induced aortic stenosis and from spontaneously hypertensive rats. J Hypertens 10:1361–1368

    Article  CAS  Google Scholar 

  • Michailova AP, Belik ME, McCulloch AD (2004) Effects of magnesium on cardiac excitation-contraction coupling. J Am Coll Nutr 23:514S–517S

    Article  CAS  Google Scholar 

  • Milnes JT, MacLeod KT (2001) Reduced ryanodine receptor to dihydropyridine receptor ratio may underlie slowed contraction in a rabbit model of left ventricular cardiac hypertrophy. J Mol Cell Cardiol 33:473–485

    Article  CAS  Google Scholar 

  • Morton JJ, Beattie EC, Speirs A, Gulliver F (1993) Persistent hypertension following inhibition of nitric oxide formation in the young Wistar rat: role of renin and vascular hypertrophy. J Hypertens 11:1083–1088

    Article  CAS  Google Scholar 

  • Ozturk N, Yaras N, Ozmen A, Ozdemir S (2013) Long-term administration of rosuvastatin prevents contractile and electrical remodelling of diabetic rat heart. J Bioenerg Biomembr 45:343–352

    Article  CAS  Google Scholar 

  • Paravicini TM, Touyz RM (2008) NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities. Diabetes Care 31: dc08–s247

  • Pollock DM (1999) Chronic studies on the interaction between nitric oxide and endothelin in cardiovascular and renal function. Clin Exp Pharmacol Physiol 26:258–261

    Article  CAS  Google Scholar 

  • Prohaska JR (1991) Changes in Cu,Zn-superoxide dismutase, cytochrome c oxidase, glutathione peroxidase and glutathione transferase activities in copper-deficient mice and rats. J Nutr 121:355–363

    CAS  Google Scholar 

  • Raju B, Murphy E, Levy LA, Hall RD, London RE (1989) A fluorescent indicator for measuring cytosolic free magnesium. Am J Phys 256:C540–C548

    CAS  Google Scholar 

  • Ren J (2007) Influence of gender on oxidative stress, lipid peroxidation, protein damage and apoptosis in hearts and brains from spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 34:432–438

    Article  CAS  Google Scholar 

  • Sharikabad MN, Ostbye KM, Lyberg T, Brors O (2001) Effect of extracellular Mg(2+) on ROS and Ca(2+) accumulation during reoxygenation of rat cardiomyocytes. Am J Physiol Heart Circ Physiol 280:H344–H353

    CAS  Google Scholar 

  • Sonoyama K, Igawa O, Miake J, Yamamoto Y, Sugihara S, Sasaki N, Shimoyama M, Hamada T, Taniguchi S, Yoshida A, Ogino K, Shigemasa C, Hoshikawa Y, Kurata Y, Shiota G, Narahashi T, Horiuchi M, Matsubara H, Ninomiya H, Hisatome I (2005) Effects of angiotensin II on the action potential durations of atrial myocytes in hypertensive rats. Hypertens Res 28:173–179

    Article  CAS  Google Scholar 

  • Sontia B, Touyz RM (2007) Role of magnesium in hypertension. Arch Biochem Biophys 458:33–39

    Article  CAS  Google Scholar 

  • Sumandea MP, Steinberg SF (2011) Redox signaling and cardiac sarcomeres. J Biol Chem 286:9921–9927

    Article  CAS  Google Scholar 

  • Tashiro M, Inoue H, Konishi M (2014) Physiological pathway of magnesium influx in rat ventricular myocytes. Biophys J 107:2049–2058

    Article  CAS  Google Scholar 

  • Touyz RM (2008) Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension. Am J Physiol Heart Circ Physiol 294:11

    Google Scholar 

  • Wang M, Berlin JR (2007) Voltage-dependent modulation of L-type calcium currents by intracellular magnesium in rat ventricular myocytes. Arch Biochem Biophys 458:65–72

    Article  CAS  Google Scholar 

  • Wang M, Tashiro M, Berlin JR (2004) Regulation of L-type calcium current by intracellular magnesium in rat cardiac myocytes. J Physiol 555:383–396

    Article  CAS  Google Scholar 

  • Wang L, Lopaschuk GD, Clanachan AS (2008) H(2)O(2)-induced left ventricular dysfunction in isolated working rat hearts is independent of calcium accumulation. J Mol Cell Cardiol 45:787–795

    Article  CAS  Google Scholar 

  • Xie LH, Chen F, Karagueuzian HS, Weiss JN (2009) Oxidative-stress-induced afterdepolarizations and calmodulin kinase II signaling. Circ Res 104:79–86

    Article  CAS  Google Scholar 

  • Zatz R, Baylis C (1998) Chronic nitric oxide inhibition model 6 years on. Hypertension 32:958–964

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from Akdeniz University Scientific Research Coordination Unit, Turkey (2011.03.0122.006). This study was carried out as PhD thesis by N. Ozturk presented to Akdeniz University Health Sciences Institute.

Author information

Authors and Affiliations

  1. Faculty of Medicine, Department of Biophysics, Akdeniz University, Antalya, Turkey

    Nihal Ozturk, Yusuf Olgar & Semir Ozdemir

  2. Faculty of Medicine, Department of Biochemistry, Akdeniz University, Antalya, Turkey

    Mutay Aslan

Authors
  1. Nihal Ozturk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yusuf Olgar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mutay Aslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Semir Ozdemir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Semir Ozdemir.

Ethics declarations

Conflict of interest

None

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ozturk, N., Olgar, Y., Aslan, M. et al. Effects of magnesium supplementation on electrophysiological remodeling of cardiac myocytes in L-NAME induced hypertensive rats. J Bioenerg Biomembr 48, 425–436 (2016). https://doi.org/10.1007/s10863-016-9666-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10863-016-9666-8

Keywords

Search

Navigation