Skip to main content
Log in

Effect of L-arginine Oral Supplementation on Response to Myocardial Infarction in Hypercholesterolemic and Hypertensive Rats

  • Original Paper
  • Published:
Plant Foods for Human Nutrition Aims and scope Submit manuscript

Abstract

The well known metabolic functions of L-arginine have been recently increased with the discovery of its role as the substrate for the synthesis of nitric oxide (NO), which has emerged as an endogenous signaling molecule with potential therapeutic implications for cardiovascular disease. Steady-state levels of NO are derived in part from dietary sources. It has been reported that supplementation of L-arginine reduces atherosclerosis in rabbits and reduces the arterial pressure in hypertensive rats. Therefore, we investigated the effect of L-arginine supplementation using a group of induced hypercholesterolemic rats and a group of spontaneously hypertensive rats; the infarcted area in cardiac tissue of both groups was measured during the response to myocardial infarction in the ischemia-reperfusion model. Hypercholesterolemic rats supplemented with 170 mg kg−1 of L-arginine showed a significant (P ≤ 0.05) reduction in total cholesterol (25.2%) and LDL (27.8%). Spontaneously hypertensive rats supplemented with L-arginine presented a significant reduction (20.3%) in mean blood pressure (P ≤ 0.05). The index infarcted area / total heart area, in both: hypercholesterolemic and hypertensive rats supplemented with L-arginine, showed a significant 36% and 29% of cardio protection (P ≤ 0.05) effect, respectively. Dietary supplementation with L-arginine may represent a potentially novel nutritional strategy for the treatment of cardiovascular disease.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ADMA:

Asymmetric dimethylarginine

C:

Total cholesterol

d:

day

g:

gram

HC:

Hypercholesterolemic

HCR:

Hypercholesterolemic rats

HDL:

High-density lipoprotein

IA:

Infarcted area

IA/TA:

Index infarcted area / Total heart area

AI:

Atherogenic index

I/R:

Ischemia-reperfusion injury

kg:

Kilogram

L:

Liter

LDL:

Low-density lipoproteins

MI/R:

Miocardial ischaemia reperfusion

NCR:

Normocholesterolemic rats

NO:

Nitric oxide

ONOO :

Peroxynitrite

0 2 :

Superoxide

NOM:

Official Mexican Regulation

NOS:

Nitric oxide synthase

NTR:

Normotensive rats

SD:

Standard desviation

SAH:

S-adenosylhomocysteine

SHR:

Spontaneously hypertensive rats

TA:

Total heart area

TG:

Triglycerides

WK:

Wistar-Kyoto rats

References

  1. Teixeira de Almeida D, Santaolaria Ayora ML, Alonso Iglesias E (2003) La arginina en su contexto metabólico y fisiológico. Acta Bioquim Clin Latinoam 37:165–179

    CAS  Google Scholar 

  2. Bryan N, Calvert J, Elrod J, Gundewar S, Yong S, Lefer D (2007) Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury. Pharmacology 48:19104–19149

    Google Scholar 

  3. Wu G, Meininger C (2000) Arginine nutrition and cardiovascular function. J Nutr 130:2626–2629

    CAS  Google Scholar 

  4. Wu G, Morris S (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17

    CAS  Google Scholar 

  5. Maxwell A, Zapien M, Pearce G, MacCallum G, Stone P (2002) Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol 39:37–45

    Article  CAS  Google Scholar 

  6. Creager M, Gallagher S, Girerd X, Dzau V, Cooke J (1992) L-arginine improves endothelium-dependent vasodilatation in hypercholesterolemic humans. J Clin Invest 90:1248–1253

    Article  CAS  Google Scholar 

  7. Chen J, Kuhlencordt P, Urano F, Ichinose H, Astern J, Huang P (2003) Effects of chronic treatment with L-arginine on atherosclerosis in ApoE knockout and ApoE/Inducible NO synthase double-knockout mice. Arterioscler Thromb Vasc Biol 23:97–103

    Article  Google Scholar 

  8. Loscalzo J (2003) Adverse effects of supplemental L-arginine in atherosclerosis. Consequences of methylation stress in a complex catabolism. Arterioscler Thromb Vasc Biol 23:3–5

    Article  CAS  Google Scholar 

  9. Ignarro L, Cirino G, Casini A (1999) Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovascular Pharmacol 34:879–886

    Article  CAS  Google Scholar 

  10. Gouvêa SA, Moysés MR, Bissoli NS, Pires JGP, Cabral AM, Abreu GR (2003) Oral administration of L-arginine decreases blood pressure and increases renal excretion of sodium and water in renovascular hypertensive rats. Braz J Med Biol Res 36:943–949

    Article  Google Scholar 

  11. Dumont Y, D’Amours M, Lebel M, Larivière R (2001) Supplementation with a low dose of L-arginine reduces blood pressure and endothelin-1 production in hypertensive uraemic rats. Nephrol Transplant 16:746–754

    Article  CAS  Google Scholar 

  12. Chang HR, Lee RP, Wu CY, Chen HI (2002) Nitric oxide in mesenteric vascular reactivity: a comparison between rats with normotension and hypertension. Clin Exp Pharmacol Physiol 29:275–280

    Article  CAS  Google Scholar 

  13. Ferdinandy P, Schulz R (2003) Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia-reperfusion injury and preconditioning. Br J Pharmacol 138:532–543

    Article  CAS  Google Scholar 

  14. Webb A, Bonnd R, Mc Lean P, Uppal R, Benjamin N, Ahluwalia A (2004) Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Pharmacology 37–101:13683–13688

    Google Scholar 

  15. Duranski MR, Greer JJM, Dejam A, Jaganmohan S, Hogg N, Langston W, Patel RP, Yet SF, Wang X, Kevil CG, Gladwin MT, Lefer DJ (2005) Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest 115:1232–1240

    CAS  Google Scholar 

  16. Norma Oficial Mexicana-062-ZOO-1999. Especificaciones Técnicas para la producción, cuidado y uso de los animales de laboratorio. Secretaría de Agricultura, Ganadería, Desarrollo Rural, Pesca y Alimentación. Estados Unidos Mexicanos

  17. Matsuda H, Chisaka T, Kubomura Y, Yamahara J, Sawada T, Fujimura H, Kimura H (1986) Effects of crude drugs on experimental hypercholesterolemia. Tea and its active principles. J Ethnopharmacol 17:213–224

    Article  CAS  Google Scholar 

  18. Zulet MA, Barber A, Garcin H, Higueret P, Martínez JA (1999) Alterations in carbohydrate and lipid metabolism induced by a diet rich in coconut oil and cholesterol in a rat model. J Am Coll Nutr 18(1):36–42

    CAS  Google Scholar 

  19. Downey J (2003) Measuring infarct size by the tetrazolium method. Available from: http://www.usouthal.edu/ishr/help/ttc/

  20. Tallarida RJ, Murray RB (1987) Manual of pharmacological calculations. Springer Verlag, New York, p 131

    Google Scholar 

  21. Böger RH, Bode-Roger SM, Mugge A, Kienke S, Brandes R, Dwenger A, Frolich JC (1995) Supplementation of hypercholesterolemic rabbits with L-arginine reduces the vascular release of superoxide anions and restores NO production. Atherosclerosis. 117:273–284

    Article  Google Scholar 

  22. Boger RH, Bode-Roger SM, Phivthong-ngam L, Brandes RP, Schwedhel E, Mugge A, Bohme M, Tsikas D, Frolich JC (1997) Dieray L-arginine and α-tocopherol reduce vascular oxidative stress and preserve endothelial function in hypercholesterolemic rabbits via different mechanisms. Atherosclerosis 141:31–43

    Article  Google Scholar 

  23. Böger RH, Bode-Böger SM, Thiele W, Creutzing A, Alexander K, Frölich JC (1998) Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol 32:1336–1344

    Article  Google Scholar 

  24. Kawano T, Nomura M, Nisikado A, Nakaya Y, Ito S (2003) Supplementation of L-arginine improves hypertension and lipids metabolism but not insulin resistance in diabetic rats. Life Sci 73:3017–3026

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Our gratitude to Alpha Program of the European Commission and to the Direction of Research (IPN-Mexico) for funding this study; to PhD Leticia Garduño Siciliano of the Preclinical Toxicology Laboratory at the National School of Biological Sciences (ENCB-IPN) and to the MS María Alejandra Guillén Orozco from the Pharmacology Department (The Superior School of Medicine-IPN).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alicia Ortiz-Moreno.

Additional information

In memory of Verónica Piñeiro who died before this article was completed.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Piñeiro, V., Ortiz-Moreno, A., Mora-Escobedo, R. et al. Effect of L-arginine Oral Supplementation on Response to Myocardial Infarction in Hypercholesterolemic and Hypertensive Rats. Plant Foods Hum Nutr 65, 31–37 (2010). https://doi.org/10.1007/s11130-009-0143-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11130-009-0143-y

Keywords

Navigation