N-Nitro-L-Arginine Methyl Ester Hydrochloride Induced Endothelial Dysfunction and Atherosclerosis Model in Rats

Year 2023, Volume: 7 Issue: 3, 114 - 121, 30.09.2023

Muhammet Kürşat Şimşek , Mustafa Mahmut Barış , Osman Yılmaz , Zekiye Altun , Safiye Aktaş , Yasemin Cakir , Sibel Büyükçoban , Mustafa Seçil

https://doi.org/10.30621/jbachs.1226509

Abstract

Purpose: Atherosclerosis (AS) related diseases are the most common causes of mortality worldwide. N-Nitro-L-Arginine Methyl Ester Hydrochloride (L-NAME)-induced endothelial dysfunction (ED) and AS models require invasive methods for diagnosis.
We aimed to establish noninvasive ultrasonography (USG) model for evaluating ED and AS in rats.
Matherial and Methods: 23 Wistar Albino rats were divided into four groups. Right CCA (rCCA), left CCA (lCCA), abdominal aorta (AA), and right iliac artery (rIA) IMT values of all rats were measured at the beginning of the experiment and before sacrification by USG. Right kidney RI values were calculated at similar times also. Histopathological and immunohistochemical analyzes were performed.
In the sham group, rats received intraperitoneally (IP) sodium chloride. In the L-NAME groups, IP L-NAME was administered.
Results: In the early effect group, significant increase was found in IMT measurements compared to the sham group.
In the late effect group, significant increase was found in IMT measurements compared to the sham group. In addition, rRI increased significantly in the group at the end of the experiment.
Conclusion: In small animal experiments which ED and AS were studied, a whole-body diagnostic noninvasive model was created for the first time with ultrasonography.

Keywords

Ultrasound, Intima-media tickness, L-NAME, renal resistive index

Supporting Institution

Dokuz Eylul University

Project Number

2019.KB.SAG.035

References

• Topol, E.J. and R.M. Califf, Textbook of cardiovascular medicine. 2007: Lippincott Williams & Wilkins.
• Onat, A., Risk factors and cardiovascular disease in Turkey. Atherosclerosis, 2001. 156(1): p. 1- 10.
• Glagov, S., et al., Compensatory enlargement of human atherosclerotic coronary arteries. New England Journal of Medicine, 1987. 316(22): p. 1371-1375.
• Ibañez, B., J.J. Badimon, and M.J. Garcia, Diagnosis of atherosclerosis by imaging. The American journal of medicine, 2009. 122(1): p. S15-S25.
• Playford, D.A. and G.F. Watts, Special article: non-invasive measurement of endothelial function. Clin Exp Pharmacol Physiol, 1998. 25(7-8): p. 640-3.
• Takase, B., et al., Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. Am J Cardiol, 1998. 82(12): p. 1535-9, a7-8.
• Schroeder, S., et al., Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery disease: pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. Am Heart J, 1999. 138(4 Pt 1): p. 731-9.
• Schächinger, V., M.B. Britten, and A.M. Zeiher, Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation, 2000. 101(16): p. 1899-1906.
• Suwaidi, J.A., et al., Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation, 2000. 101(9): p. 948-54.
• Faulx, M.D., A.T. Wright, and B.D. Hoit, Detection of endothelial dysfunction with brachial artery ultrasound scanning. Am Heart J, 2003. 145(6): p. 943-51.
• Woo, K., et al., Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening. International journal of obesity, 2004. 28(7): p. 852-857.
• Järvisalo, M.J., et al., Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children. Circulation, 2001. 104(24): p. 2943-2947.
• Xiangdong, L., et al., Animal models for the atherosclerosis research: a review. Protein & cell, 2011. 2(3): p. 189-201.
• Khayyal, M.T., et al., Blood pressure lowering effect of an olive leaf extract (Olea europaea) in L-NAME induced hypertension in rats. Arzneimittelforschung, 2002. 52(11): p. 797-802.
• Pechanova, O., et al., Red wine polyphenols prevent cardiovascular alterations in L-NAMEinduced hypertension. J Hypertens, 2004. 22(8): p. 1551-9.
• Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation, 1986 Dec; 74(6):1399-406.
• Park, K., et al., Initial validation of a novel rat model of vasculogenic erectile dysfunction with generalized atherosclerosis. International journal of impotence research, 2005. 17(5): p. 424- 430.
• Wang, H.-t., et al., Guidelines for assessing mouse endothelial function via ultrasound imaging: a report from the International Society of Cardiovascular Translational Research. Journal of cardiovascular translational research, 2015. 8(2): p. 89-95
• Kemmner S, Lorenz G, Wobst J, Kessler T, Wen M, Günthner R, Stock K, Heemann U, Burkhardt K, Baumann M, Schmaderer C. Dietary nitrate load lowers blood pressure and renal resistive index in patients with chronic kidney disease: A pilot study. Nitric Oxide. 2017 Apr 1; 64:7-15. doi: 10.1016/j.niox.2017.01.011. Epub 2017 Jan 28. PMID: 28137609.
• Sugiura T, Nakamori A, Wada A, Fukuhara Y. Evaluation of tubulointerstitial injury by Doppler ultrasonography in glomerular diseases. Clin Nephrol. 2004 Feb;61(2):119-26. doi: 10.5414/cnp61119. PMID: 14989631.
• Ikee R, Kobayashi S, Hemmi N, Imakiire T, Kikuchi Y, Moriya H, Suzuki S, Miura S. Correlation between the resistive index by Doppler ultrasound and kidney function and histology. Am J Kidney Dis. 2005 Oct;46(4):603-9. doi: 10.1053/j.ajkd.2005.06.006. PMID: 16183414.
• Bigé N, Lévy PP, Callard P, Faintuch JM, Chigot V, Jousselin V, Ronco P, Boffa JJ. Renal arterial resistive index is associated with severe histological changes and poor renal outcome during chronic kidney disease. BMC Nephrol. 2012 Oct 25; 13:139. doi: 10.1186/1471-2369-13-139. PMID: 23098365; PMCID: PMC3531254.
• Aktürk, Zekeriya, and Hamit Acemoğlu. "Tıbbi araştırmalarda güvenilirlik ve geçerlilik." Dicle Tıp Dergisi 39.2 (2012): 316-319.
• Gan, L.-m., et al., Non-invasive real-time imaging of atherosclerosis in mice using ultrasound biomicroscopy. Atherosclerosis, 2007. 190(2): p. 313-320.
• Sohn, E.J., et al., Effect of methanol extract of Sorbus cortex in a rat model of L-NAME-induced atherosclerosis. Biol Pharm Bull, 2005. 28(7): p. 1239-43
• Pontremoli, R., et al., Increased renal resistive index in patients with essential hypertension: a marker of target organ damage. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association-European Renal Association, 1999. 14(2): p. 360-365.
• Karakus, S., et al., The effect of enalapril on renal resistive index, urine electrolyte levels and tgf-β1 levels of kidney tissues in rats with unilateral partial ureteropelvic junction obstruction. European Journal of Pediatric Surgery, 2011. 21(06): p. 356-361