Experimental models for vascular endothelial dysfunction

Keywords: Experimental model, Mini-review, Vascular endothelial dysfunction
DOI: 10.3329/bjp.v16i3.52948


Vascular endothelial dysfunction is characterized by apoptosis of endothelial cells, an imbalance between vasoconstrictory and vasodilatory substances, the imbalance between ROS and antioxidants, vascular remodeling, loss of vascular integrity which leads to an increased risk of cardiovascular complications. To date, no therapeutic intervention is available as a promising agent. This may be due to a poor understanding of the underlying mechanism involved in vascular endothelial dysfunction in the pathogenesis. Animal models sharing identical features as that of humans are paramount to understand fundamental physiology, mechanism and to explore new targets for developing therapeutic agents. Thus, it becomes mandatory to re-explore the available animal models for a better understanding of molecular pathways involving vascular endothelial dysfunction. The purpose of this paper is to review different models for vascular endothelial dysfunction to the outlook for developing new drugs to treat vascular endothelial dysfunction.


The vascular endothelium is the innermost lining of the blood vessel. It is a metabolically active layer that tends to release various substances that control vascular relaxation and contraction as well as enzymes that control blood clotting, immune function, and platelet adhesion (Sandoo et al., 2010). It plays a crucial role in maintaining vascular tone, integrity, and free flow of the blood under normal physiology. Destruction or injury in the endothelial layer of arteries leads to create an imbalance between vasoconstriction and vasodilatation factors which complicate vascular endothelial dysfunction and lead to cause various other severe cardiovascular disorders. An increase in free radicle production (ROS/RNS), NADPH oxidase, xanthin-oxidase or decrease in glutathione, no generation is the underlying pathways involved in the pathogenesis of vascular endothelial dysfunction. Regulation of inflammatory mediators such as intracellular adhesion molecule-1, von Willi brand factor, Nf-kb and growth factors like endothelin-1, VEGF, PDGF, OLGF, and ILs mutually affect vascular endothelium (Balakumar et al., 2008a). Atherosclerosis, hypertension, hyperglycemia, and smoking are considered to be the self-governing risk factors and foremost determinants in the progression of vascular endothelial dysfunction (Hadi et al., 2005). To identify the potential pharmacological targets for vascular endothelial dysfunction in different experimental models are designed and employed to induce the vascular endothelial dysfunction. Therefore, this paper aims to review various experimental animal models developed to produce vascular endothelial dysfunction.  


To understand complex pathogenesis and to develop a new therapeutic alternative for treating vascular endothelial dysfunction animal models are widely used. Continued utilization of these experimental models simulating human vascular endothelial dysfunction, particularly those that combine other clinically relevant comorbidities like obesity, nicotine intake, hyperuricemia or hypercholesterolemia, may open a new vista in development of effective strategies to address the vascular complications. Nevertheless, a restrained methodology is mandatory while experimental find-ings in these models are extrapolated to human vascular endothelial dysfunction. 

Author Biography

Mandeep Kumar Arora, School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun 248009, Uttarakhand, India.

Associate Professor


Abo Zeid AA, Rowida Raafat I, Ahmed AG. Berberine alleviates monosodium glutamate induced postnatal metabolic disorders associated vascular endothelial dysfunction in newborn rats: Possible role of matrix metalloproteinase-1. Arch Physiol Biochem. 2020; 19: 1-12.

Adel H, Taye A, Khalifa MM. Spironolactone improves endothelial dysfunction in streptozotocin-induced diabetic rats. Naunyn Schmiedebergs Arch Pharmacol. 2014; 387: 1187-97.

Akaike M, Matsumoto T. Glucocorticoid-induced reduction in NO bioavailability and vascular endothelial dysfunction. Clin Calcium. 2007; 17: 864-70.

Alarcon G, Roco J, Medina M, Medina A, Peral M, Jerez S. High fat diet-induced metabolically obese and normal weight rabbit model shows early vascular dysfunction: Mechanisms involved. Int J Obes (Lond). 2018; 42: 1535-43.

Azemi AK, Mokhtar SS, Rasool AHG. Clinacanthus nutans leaves extract reverts endothelial dysfunction in type 2 diabetes rats by improving protein expression of eNOS. Oxid Med Cell Longev. 2020; 2020.

Babacanoglu C, Yildirim N, Sadi G, Pektas MB, Akar F. Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance and dysfunction in rats. Food Chem Toxicol. 2013; 60: 160-67.

Baig MA, Panchal SS. Streptozotocin-induced diabetes mellitus in neonatal rats: An insight into its applications to induce diabetic complications. Curr Diabetes Rev. 2019; 16: 26-39.

Balakumar P, Chakkarwar VA, Kumar V, Jain A, Reddy J, Singh M. Experimental models for nephropathy. J Renin Angiotensin Aldosterone Syst. 2008a; 9: 189-95.

Balakumar P, Chakkarwar VA, Singh M. Ameliorative effect of combination of benfotiamine and fenofibrate in diabetes-induced vascular endothelial dysfunction and nephropathy in the rat. Mol Cell Biochem. 2009; 320: 149-62.

Balakumar P, Jindal S, Shah DI, Singh M. Experimental models for vascular endothelial dysfunction. Trends Med Res. 2007; 2: 12-20.

Balakumar P, Kaur T, Singh M. Potential target sites to modulate vascular endothelial dysfunction: Current perspectives and future directions. Toxicology 2008b; 245: 49-64.

Balakumar P, Sharma R, Singh M. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat. Pharmacol Res. 2008c; 58: 356-63.

Basso N, Ruiz P, Kurnjek ML, Cannata MA, Taquini AC. The brain renin-angiotensin system and the development of DOC-salt hypertension. Clin Exp Hypertension. 1985; A7: 1259-68.

Brahmanaidu P, Uddandrao VVS, Sasikumar V, Naik RR, Pothani S, Begum MS, Rajeshkumar MP, Varatharaju C, Meriga B, Rameshreddy P, Kalaivani A, Saravanan G. Reversal of endothelial dysfunction in aorta of streptozotocin-nicotinamide-induced type-2 diabetic rats by S-allylcysteine. Mol Cell Biochem. 2017; 432: 25-32.

Capellini VK, Baldo CF, Celotto AC, Batalhão ME, Cárnio EC, Rodrigues AJ, Evora PR. Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats. Arq Bras Endocrinol Metabol. 2010; 54: 530-39.

Carvalho C, Santos RX, Cardoso S, Correia S, Oliveira PJ, Santos MS, Moreira PI. Doxorubicin: The good, the bad and the ugly effect. Curr Med Chem. 2009; 16: 3267-85.

Chakkarwar VA. Fenofibrate attenuates nicotine-induced vascular endothelial dysfunction in the rat. Vascul Pharmacol. 2011; 55: 163-68.

Chi L, Hu X, Zhang W, Bai T, Zhang L, Zeng H, Guo R, Zhang Y, Tian H. Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats. Biochem Biophys Res Commun. 2017; 482: 727-34.

Chuaiphichai S, Starr A, Nandi M, Channon KM, McNeill E. Endothelial cell tetrahydrobiopterin deficiency attenuates LPS-induced vascular dysfunction and hypotension. Vascul Pharmacol. 2016; 77: 69-79.

Clayton ZS, Brunt VE, Hutton DA, VanDongen NS, D'Alessandro A, Reisz JA, Ziemba BP, Seals DR. Doxorubicin-induced oxidative stress and endothelial dysfunction in conduit arteries is prevented by mitochondrial-specific antioxidant treatment. JACC Cardio Oncol. 2020; 2: 475-88.

Dai J, Chen W, Lin Y, Wang S, Guo X, Zhang QQ. Exposure to concentrated ambient fine particulate matter induces vascular endothelial dysfunction via miR-21. Int J Biol Sci. 2017; 13: 868-77.

Dikalova AE, Pandey A, Xiao L, Arslanbaeva L, Sidorova T, Lopez MG, Billings FT 4th, Verdin E, Auwerx J, Harrison DG, Dikalov SI. Mitochondrial deacetylase Sirt3 reduces vascular dysfunction and hypertension while Sirt3 depletion in essential hypertension is linked to vascular inflammation and oxidative stress. Circ Res. 2020; 126: 439-52.

Ding Y, Zhang B, Zhou K, Chen M, Wang M, Jia Y, Song Y, Li Y, Wen A. Dietary ellagic acid improves oxidant-induced endothelial dysfunction and atherosclerosis: Role of Nrf2 activation. Int J Cardiol. 2014; 175: 508-14.

Echeverría C, Montorfano I, Tapia P, Riedel C, Cabello-Verrugio C, Simon F. Endotoxin-induced endothelial fibrosis is dependent on expression of transforming growth factors β1 and β2. Infect Immun. 2014; 82: 3678-86.

El-Bassossy HM, Dsokey N, Fahmy A. Characterization of vascular complications in experimental model of fructose-induced metabolic syndrome. Toxicol Mech Methods. 2014; 24: 536-43.

Ellinsworth DC. Arsenic, reactive oxygen, and endothelial dysfunction. J Pharmacol Exp Ther. 2015; 353: 458-64.

Esse R, Barroso M, Tavares de Almeida I, Castro R. The contribution of homocysteine metabolism disruption to endothelial dysfunction: State-of-the-art. Int J Mol Sci. 2019; 20: 867.

Fadini GP, Avogaro A. Cell-based methods for ex vivo evaluation of human endothelial biology. Cardiovasc Res. 2010; 87: 12-21.

Fathallah-Shaykh SA, Cramer MT. Uric acid and the kidney. Pediatr Nephrol. 2014; 29: 999-1008.

Friques AGF, Santos FDN, Angeli DB, Silva FAC, Dias AT, Aires R, Leal MAS, Nogueira BV, Amorim FG, Campagnaro BP, Pereira TMC, Campos-Toimil M, Meyrelles SS, Vasquez EC. Bisphenol A contamination in infant rats: Molecular, structural, and physiological cardiovascular changes and the protective role of kefir. J Nutr Biochem. 2020; 75: 108254.

Guo J, Wang Z, Wu J, Liu M, Li M, Sun Y, Huang W, Li Y, Zhang Y, Tang W, Li X, Zhang C, Hong F, Li N, Nie J, Yi F. Endothelial SIRT6 is vital to prevent hypertension and associated cardiorenal injury through targeting Nkx3.2-GATA5 signalling. Circ Res. 2019a; 124: 1448-61.

Guo X, Fu X, Liu X, Wang J, Li Z, Gao L, Li Y, Zhang W. Role of pigment epithelium-derived factor in arsenic-induced vascular endothelial dysfunction in a rat model. Biol Trace Elem Res. 2019b; 190: 405-13.

Guo X, Liu X, Wang J, Fu X, Yao J, Zhang X, Jackson S, Li J, Zhang W, Sun D. Pigment epithelium-derived factor (PEDF) ameliorates arsenic-induced vascular endothelial dysfunction in rats and toxicity in endothelial EA. hy926 cells. Environ Res. 2020; 186: 109506.

Hadi HA, Carr CS, Al Suwaidi J. Endothelial dysfunction: Cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag. 2005; 1: 183-98.

Han S, Bal NB, Sadi G, Usanmaz SE, Tuglu MM, Uludag MO, Demirel-Yilmaz E. Inhibition of endoplasmic reticulum stress protected DOCA-salt hypertension-induced vascular dysfunction. Vascul Pharmacol. 2019; 113: 38-46.

Huang JP, Hsu SC, Li DE, Chen KH, Kuo CY, Hung LM. Resveratrol mitigates high-fat diet-induced vascular dysfunction by activating the Akt/eNOS/NO and Sirt1/ER pathway. J Cardiovasc Pharmacol. 2018; 72: 231-41.

Huang X, Zhu J, Jiang Y, Xu C, Lv Q, Yu D, Shi K, Ruan Z, Wang Y. SU5416 attenuated lipopolysaccharide-induced acute lung injury in mice by modulating properties of vascular endothelial cells. Drug Des Devel Ther. 2019; 13: 1763-72.

Ji B, Yuan K, Li J, Ku BJ, Leung PS, He W. Protocatechualdehyde restores endothelial dysfunction in streptozotocin-induced diabetic rats. Ann Transl Med. 2021a; 9: 711.

Ji XW, Lyu HJ, Zhou GH, Wu B, Zhu YY, Wu TH, Zhang F, Jin SN, Cho KW, Wen JF. Physcion, a tetra-substituted 9,10-anthraquinone, prevents homocysteine-induced endothelial dysfunction by activating Ca2+- and Akt-eNOS-NO signaling pathways. Phytomedicine 2021b; 81: 153410.

Jyoti U, Kansal SK, Kumar P, Goyal S. Possible vasculoprotective role of linagliptin against sodium arsenite-induced vascular endothelial dysfunction. Naunyn Schmiedebergs Arch Pharmacol. 2016; 389: 167-75.

Kaur T, Goel RK, Balakumar P. Effect of rosiglitazone in sodium arsenite-induced experimental vascular endothelial dysfunction. Arch Pharm Res. 2010; 33: 611-18.

Kesavan M, Sarath TS, Kannan K, Suresh S, Gupta P, Vijayakaran K, Sankar P, Kurade NP, Mishra SK, Sarkar SN. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators. Toxicol Appl Pharmacol. 2014; 280: 107-16.

Khitan Z, Kim DH. Fructose: A key factor in the development of metabolic syndrome and hypertension. J Nutr Metab. 2013; 2013.

Kho MC, Lee YJ, Cha JD, Choi KM, Kang DG, Lee HS. Gastrodia elata ameliorates high-fructose diet-induced lipid metabolism and endothelial dysfunction. Evid Based Complement Alternat Med. 2014; 2014.

Kruger N, Biwer LA, Good ME, Ruddiman CA, Wolpe AG, DeLalio LJ, Murphy S, Macal EH Jr, Ragolia L, Serbulea V, Best AK, Leitinger N, Harris TE, Sonkusare SK, Gödecke A, Isakson BE. Loss of endothelial FTO antagonizes obesity-induced metabolic and vascular dysfunction. Circ Res. 2020; 126: 232-42.

Kshirsagar RP, Chouthe RS, Reddy GB, Bhardwaj DK, Diwan PV. Geraniol ameliorates endothelial dysfunction in streptozotocin-induced diabetic rats. J Pharm Res. 2017; 11: 1159-65.

Kubacka M, Zadrożna M, Nowak B, Kotańska M, Filipek B, Waszkielewicz AM, Marona H, Mogilski S. Reversal of cardiac, vascular, and renal dysfunction by non-quinazoline α1-adrenolytics in DOCA-salt hypertensive rats: A comparison with prazosin, a quinazoline-based α1-adrenoceptor antagonist. Hypertens Res. 2019; 42: 1125-41.

Kumar BH, Reddy AR, Kumar JM, Bhardwaj DK, Diwan PV. Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia. Can J Physiol Pharmacol. 2017; 95: 32-42.

Lan TH, Xu ZW, Wang Z, Wu YL, Wu WK, Tan HM. Ginsenoside Rb1 prevents homocysteine-induced endothelial dysfunction via PI3K/Akt activation and PKC inhibition. Biochem Pharmacol. 2011; 82: 148-55.

Le Brocq M, Leslie SJ, Milliken P, Megson IL. Endothelial dysfunction: From molecular mechanisms to measurement, clinical implications, and therapeutic opportunities. Antioxid Redox Signal. 2008; 10: 1631-74.

Leao VF, Ferreira LLDM, Melo CM, Bonfleur ML, da Silva LL, Carneiro EM, Raimundo JM, Ribeiro RA. Taurine supplementation prevents endothelial dysfunction and attenuates structural changes in aortas from hypothalamic obese rats. Eur J Nutr. 2019; 58: 551-63.

Li H, Lu W, Cai WW, Wang PJ, Zhang N, Yu CP, Wang DL, Liu BC, Sun W. Telmisartan attenuates monocrotaline-induced pulmonary artery endothelial dysfunction through a PPAR gamma-dependent PI3K/Akt/eNOS pathway. Pulm Pharmacol Ther. 2014; 28: 17-24.

Li X, Gu J, Zhang Y, Feng S, Huang X, Jiang Y, Xia Y, Liu Y, Yang X. l-arginine alleviates doxorubicin-induced endothelium-dependent dysfunction by promoting nitric oxide generation and inhibiting apoptosis. Toxicology 2019; 423: 105-11.

Liang S, Zhao T, Hu H, Shi Y, Xu Q, Miller MR, Duan J, Sun Z. Repeat dose exposure of PM2.5 triggers the disseminated intravascular coagulation (DIC) in SD rats. Sci Total Environ. 2019; 663: 245-53.

Liu C, Zhou MS, Li Y, Wang A, Chadipiralla K, Tian R, Raij L. Oral nicotine aggravates endothelial dysfunction and vascular inflammation in diet-induced obese rats: Role of macrophage TNFα. PLoS One. 2017; 12: e0188439.

Liu Y, Cole V, Lawandy I, Ehsan A, Sellke FW, Feng J. Decreased coronary arteriolar response to KCa channel opener after cardioplegic arrest in diabetic patients. Mol Cell Biochem. 2018; 445: 187-94.

Lobato NS, Filgueira FP, Akamine EH, Davel AP, Rossoni LV, Tostes RC, Carvalho MH, Fortes ZB. Obesity induced by neonatal treatment with monosodium glutamate impairs microvascular reactivity in adult rats: Role of NO and prostanoids. Nutr Metab Cardiovasc Dis. 2011; 21: 808-16.

Lynn WA, Golenbock DT. Lipopolysaccharide antagonists. Immunol Today. 1992; 13: 271-76.

Malakul W, Pengnet S, Kumchoom C, Tunsophon S. Naringin ameliorates endothelial dysfunction in fructose-fed rats. Exp Ther Med. 2018; 15: 3140-46.

Moretti R, Caruso P. The controversial role of homocysteine in neurology: From labs to clinical practice. Int J Mol Sci. 2019; 20: 231.

Nacci C, Tarquinio M, De Benedictis L, Mauro A, Zigrino A, Carratù MR, Quon MJ, Montagnani M. Endothelial dysfunction in mice with streptozotocin-induced type 1 diabetes is opposed by compensatory overexpression of cyclooxygenase-2 in the vasculature. Endocrinology 2009; 150: 849-61.

Niaz K, Zaplatic E, Spoor J. Extensive use of monosodium glutamate: A threat to public health? EXCLI J. 2018; 17: 273-78.

Niazi ZR, Najmanová I, Kamagaté M, Said A, Chabert P, Auger C, DieKakou H, Schini-Kerth V. Preventive beneficial effect of an aqueous extract of Phyllanthus amarus Schum. and Thonn. (Euphorbiaceae) on DOCA-salt–induced hypertension, cardiac hypertrophy and dysfunction, and endothelial dysfunction in rats. J Cardiovasc Pharmacol. 2020; 75: 573-83.

Nie Q, Zhu L, Zhang L, Leng B, Wang H. Astragaloside IV protects against hyperglycemia-induced vascular endothelial dysfunction by inhibiting oxidative stress and calpain-1 activation. Life Sci. 2019; 232: 116662.

Oelze M, Knorr M, Schuhmacher S, Heeren T, Otto C, Schulz E, Reifenberg K, Wenzel P, Münzel T, Daiber A. Vascular dysfunction in streptozotocin-induced experimental diabetes strictly depends on insulin deficiency. J Vasc Res. 2011; 48: 275-84.

Olatunji LA, Seok YM, Igunnu A, Kang SH, Kim IK. Combined oral contraceptive-induced hypertension is accompanied by endothelial dysfunction and up-regulated intrarenal angiotensin II type 1 receptor gene expression. Naunyn Schmiedebergs Arch Pharmacol. 2016; 389: 1147-57.

Olukman M, Can C, Erol A, Oktem G, Oral O, Cinar MG. Reversal of doxorubicin-induced vascular dysfunction by resveratrol in rat thoracic aorta: Is there a possible role of nitric oxide synthase inhibition? Anadolu Kardiyol Derg. 2009; 9: 260-66.

Oyabambi AO, Areola ED, Olatunji LA, Soladoye AO. Uric acid is a key player in salt-induced endothelial dysfunction: The therapeutic role of Stigma maydis (corn silk) extract. Appl Physiol Nutr Metab. 2020; 45: 67-71.

Pal PB, Sonowal H, Shukla K, Srivastava SK, Ramana KV. Aldose reductase regulates hyperglycemia-induced HUVEC death via SIRT1/AMPK-α1/mTOR pathway. J Mol Endocrinol. 2019; 63: 11-25.

Pieper GM, Langenstroer P, Siebeneich W. Diabetic-induced endothelial dysfunction in rat aorta: Role of hydroxyl radicals. Cardiovasc Res. 1997; 34: 145-56.

Qimuge A, Liu S, Wang H, Hu M, Song L. MAPK/AP-1 pathway activation mediates AT1R up-regulation and vascular endothelial cells dysfunction under PM2.5 exposures. Ecotoxicol Environ Saf. 2019; 170: 188-94.

Qin W, Zhang L, Li Z, Xiao D, Zhang Y, Zhang H, Mokembo JN, Monayo SM, Jha NK, Kopylov P, Shchekochikhin D, Zhang Y. Endothelial to mesenchymal transition contributes to nicotine-induced atherosclerosis. Theranostics 2020; 10: 5276-89.

Radovits T, Arif R, Bömicke T, Korkmaz S, Barnucz E, Karck M, Merkely B, Szabó G. Vascular dysfunction induced by hypochlorite is improved by the selective phosphodiesterase-5-inhibitor vardenafil. Eur J Pharmacol. 2013; 710: 110-19.

Rameshrad M, Imenshahidi M, Razavi BM, Iranshahi M, Hosseinzadeh H. Bisphenol A vascular toxicity: Protective effect of Vitis vinifera (grape) seed extract and resveratrol. Phytother Res. 2018; 32: 2396-407.

Ren H, Mu J, Ma J, Gong J, Li J, Wang J, Gao T, Zhu P, Zheng S, Xie J, Yuan B. Selenium inhibits homocysteine-induced endothelial dysfunction and apoptosis via activation of AKT. Cell Physiol Biochem. 2016; 38: 871-82.

Reventun P, Sanchez-Esteban S, Cook A, Cuadrado I, Roza C, Moreno-Gomez-Toledano R, Muñoz C, Zaragoza C, Bosch RJ, Saura M. Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway. Sci Rep. 2020; 10: 4190.

Ross EJ, Linch DC. Cushing's syndrome- killing disease: Discriminatory value of signs and symptoms aiding early diagnosis. Lancet 1982; 2: 646-69.

Sahara M, Sata M, Morita T, Hirata Y, Nagai R. Nicorandil attenuates monocrotaline-induced vascular endothelial damage and pulmonary arterial hypertension. PLoS One. 2012; 7: e33367.

Said MA. Vitamin D attenuates endothelial dysfunction in streptozotocin-induced diabetic rats by reducing oxidative stress. Arch Physiol Biochem. 2020; 1: 1-5.

Sandoo A, van Zanten JJ, Metsios GS, Carroll D, Kitas GD. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J. 2010; 4: 302-12.

Saura M, Marquez S, Reventun P, Olea-Herrero N, Arenas MI, Moreno-Gómez-Toledano R, Gómez-Parrizas M, Muñóz-Moreno C, González-Santander M, Zaragoza C, Bosch RJ. Oral administration of bisphenol A induces high blood pressure through angiotensin II/CaMKII-dependent uncoupling of eNOS. FASEB J. 2014; 28: 4719-28.

Schafer SC, Wallerath T, Closs EI, Schmidt C, Schwarz PM, Forstermann U, Lehr HA. Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles. Am J Physiol Heart Circ Physiol. 2005; 288: H436-44.

Schenk J, McNeill JH. The pathogenesis of DOCA-salt hypertension. J Pharmacol Toxicol Methods. 1992; 27: 161-70.

Shawky NM, Shehatou GS, Abdel Rahim M, Suddek GM, Gameil NM. Levocetirizine ameliorates high fructose diet-induced insulin resistance, vascular dysfunction and hepatic steatosis in rats. Eur J Pharmacol. 2014; 740: 353-63.

Si LY, Kamisah Y, Ramalingam A, Lim YC, Budin SB, Zainalabidin S. Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats. Appl Physiol Nutr Metab. 2017; 42: 765-72.

Steven S, Oelze M, Brandt M, Ullmann E, Kröller-Schön S, Heeren T, Tran LP, Daub S, Dib M, Stalleicken D, Wenzel P, Münzel T, Daiber A. Pentaerythritol tetranitrate in vivo treatment improves oxidative stress and vascular dysfunction by suppression of endothelin-1 signaling in monocrotaline-induced pulmonary hypertension. Oxid Med Cell Longev. 2017; 2017: 4353462.

Taddei S, Virdis A, Ghiadoni L, Sudano I, Salvetti A. Endothelial dysfunction in hypertension. J Cardiovasc Pharm. 2001; 38: S11-14.

Taneja G, Mahadevan N, Balakumar P. Fish oil blunted nicotine-induced vascular endothelial abnormalities possibly via activation of PPARγ-eNOS-NO signals. Cardiovasc Toxicol. 2013; 13: 110-22.

Tian R, Ding Y, Peng YY, Lu N. Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid. Biochem Biophys Res Commun. 2017; 484: 572-78.

Ueno Y, Mohara O, Brosnihan KB, Ferrario CM. Characteristics of hormonal and neurogenie mechanisms of DOC-induced hypertension. Hypertension 1988; 11: 172-77.

Wang X, Chen L, Wang T, Jiang X, Zhang H, Li P, Lv B, Gao X. Ginsenoside Rg3 antagonizes adriamycin-induced cardiotoxicity by improving endothelial dysfunction from oxidative stress via up-regulating the Nrf2-ARE pathway through the activation of AKT. Phytomedicine 2015; 22: 875-84.

Wang XJ, Tian DC, Wang FW, Zhang MH, Fan CD, Chen W, Wang MH, Fu XY, Ma JK. Astaxanthin inhibits homocysteine induced endothelial cell dysfunction via the regulation of the reactive oxygen species-dependent VEGF VEGFR2 FAK signaling pathway. Mol Med Rep. 2019; 19: 4753-60.

Wassmann S, Bäumer AT, Strehlow K, Van Eickels M, Grohé C, Ahlbory K, Rösen R, Böhm M, Nickenig G. Endothelial dysfunction and oxidative stress during estrogen deficiency in spontaneously hypertensive rats. Circulation 2001; 103: 435-41.

Wu H, Wu J, Zhou S, Huang W, Li Y, Zhang H, Wang J, Jia Y. SRT2104 attenuates diabetes-induced aortic endothelial dysfunction via inhibition of P53. J Endocrinol. 2018; 237: 1-14.

Yang S, Zhang L. Glucocorticoids and vascular reactivity. Curr Vasc Pharmacol. 2004; 2: 1-12.

Yang XY, Qiang GF, Zhang L, Zhu XM, Wang SB, Sun L, Yang HG, Du GH. Salvianolic acid A protects against vascular endothelial dysfunction in high-fat diet fed and streptozotocin-induced diabetic rats. J Asian Nat Prod Res. 2011; 13: 884-94.

Yin Y, Qi F, Song Z, Zhang B, Teng J. Ferulic acid combined with astragaloside IV protects against vascular endothelial dysfunction in diabetic rats. Biosci Trends. 2014; 8: 217-26.

Zhai X, Ren D, Luo Y, Hu Y, Yang X. Chemical characteristics of an Ilex Kuding tea polysaccharide and its protective effects against high fructose-induced liver injury and vascular endothelial dysfunction in mice. Food Funct. 2017; 8: 2536-47.

Zhang Y, Chen Y, Zhang Y, Li PL, Li X. Contribution of cathepsin B-dependent Nlrp3 inflammasome activation to nicotine-induced endothelial barrier dysfunction. Eur J Pharmacol. 2019; 865: 172795.

Zhao YX, Tong L, Zhang GM, Zhao XH, Sa YP, Liu Y, Lu DX, Ga Q, Wu P. L-Arginine supplementation improves vascular endothelial dysfunction induced by high-fat diet in rats exposed to hypoxia. Wilderness Environ Med. 2020; 31: 400-06.

Zhu J, Wang CG, Xu YG. Lycopene attenuates endothelial dysfunction in streptozotocin-induced diabetic rats by reducing oxidative stress. Pharm Biol. 2011; 49: 1144-49.


Apply citation style format of Bangladesh Journal of Pharmacology

Mini Review
Financial Support
Conflict of Interest
Authors declare no conflict of interest