Beneficial effects of grape seed proanthocyanidin extract on arterial remodeling in spontaneously hypertensive rats via protecting against oxidative stress

Liang,Ying; Wang,Jian; Gao,Haiqing; Wang,Quanzhen; Zhang,Jun; Qiu,Jie

doi:10.3892/mmr.2016.5699

Beneficial effects of grape seed proanthocyanidin extract on arterial remodeling in spontaneously hypertensive rats via protecting against oxidative stress

Authors:
- Ying Liang
- Jian Wang
- Haiqing Gao
- Quanzhen Wang
- Jun Zhang
- Jie Qiu
View Affiliations

Affiliations: Department of Geriatric Cardiology, Qianfoshan Hospital of Shandong University, Jinan, Shandong 250013, P.R. China, Department of Geriatric Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: September 1, 2016 https://doi.org/10.3892/mmr.2016.5699
Pages: 3711-3718

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Arterial remodeling is a pathogenic occurrence during hypertension and, in turn, is closely associated with the development and complications of hypertension. Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a protective effect on cardiovascular disease, however its effect on arterial remodeling remains to be fully elucidated. In the present study, the effects of GSPE on arterial remodeling were analyzed by treating spontaneously hypertensive rats (SHRs) with GSPE (250 mg/kg·day). Arterial remodeling was quantified through morphological methods; thoracic aortas were stained with hematoxylin-eosin or sirius red‑victoria blue. The arterial ultrastructure was imaged using transmission electron microscopy. The content of nitric oxide (NO) and endothelin‑1 (ET‑1) were examined to determine endothelial function. Oxidative stress was assessed by malondialdehyde (MDA) levels and the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Administration of GSPE markedly alleviated hypertension‑induced arterial remodeling, which was not associated with blood pressure control. ET‑1 production was reduced, while NO production was increased in the GSPE group, which exhibited improved endothelial function. In addition, treatment with GSPE significantly ameliorated oxidative stress by improving SOD and CAT activities and reducing MDA formation. In conclusion, GSPE may attenuate hypertension‑induced arterial remodeling by repressing oxidative stress and is recommended as a potential anti‑arterial remodeling agent for patients with hypertensive vascular diseases.

View Figures

View References

1	Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, et al: Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 42:1206–1252. 2003. View Article : Google Scholar : PubMed/NCBI
2	Behradmanesh S and Nasri P: Serum cholesterol and LDL-C in association with level of diastolic blood pressure in type 2 diabetic patients. J Renal Inj Prev. 1:23–26. 2012.PubMed/NCBI
3	Intengan HD and Schiffrin EL: Vascular remodeling in hypertension: Roles of apoptosis, inflammation, and fibrosis. Hypertension. 38:581–587. 2001. View Article : Google Scholar : PubMed/NCBI
4	Tousoulis D, Briasoulis A, Papageorgiou N, Tsioufis C, Tsiamis E, Toutouzas K and Stefanadis C: Oxidative stress and endothelial function: Therapeutic interventions. Recent Pat Cardiovasc Drug Discov. 6:103–114. 2011. View Article : Google Scholar : PubMed/NCBI
5	Cakir Y and Ballinger SW: Reactive species-mediated regulation of cell signaling and the cell cycle: The role of MAPK. Antioxid Redox Signal. 7:726–740. 2005. View Article : Google Scholar : PubMed/NCBI
6	Lyle AN and Griendling KK: Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology (Bethesda). 21:269–280. 2006. View Article : Google Scholar
7	McIntyre M, Bohr DF and Dominiczak AF: Endothelial function in hypertension: The role of superoxide anion. Hypertension. 34:539–545. 1999. View Article : Google Scholar : PubMed/NCBI
8	Berk BC: Redox signals that regulate the vascular response to injury. Thromb Haemost. 82:810–817. 1999.PubMed/NCBI
9	Cave AC, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ, Walker S and Shah AM: NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal. 8:691–728. 2006. View Article : Google Scholar : PubMed/NCBI
10	Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J and Stohs SJ: Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. Gen Pharmacol. 30:771–776. 1998. View Article : Google Scholar : PubMed/NCBI
11	Liu X, Qiu J, Zhao S, You B, Ji X, Wang Y, Cui X, Wang Q and Gao H: Grape seed proanthocyanidin extract alleviates ouabain-induced vascular remodeling through regulation of endothelial function. Mol Med Rep. 6:949–954. 2012.PubMed/NCBI
12	Li XL, Li BY, Gao HQ, Cheng M, Xu L, Li XH and Ma YB: Effects of grape seed proanthocyanidin extracts on aortic pulse wave velocity in streptozocin induced diabetic rats. Biosci Biotechnol Biochem. 73:1348–1354. 2009. View Article : Google Scholar : PubMed/NCBI
13	Guide for the Care and Use of Laboratory Animals. National Research Council (US) Institute for Laboratory Animal Research, National Academies Press (US); Washington (DC): 1996
14	Rizzoni D, Paiardi S, Rodella L, Porteri E, De Ciuceis C, Rezzani R, Boari GE, Zani F, Miclini M, Tiberio GA, et al: Changes in extracellular matrix in subcutaneous small resistance arteries of patients with primary aldosteronism. J Clin Endocrinol Metab. 91:2638–2642. 2006. View Article : Google Scholar : PubMed/NCBI
15	Lopez-Andres N, Fortuno MA, Diez J, Zannad F, Lacolley P and Rossignol P: Vascular effects of cardiotrophin-1: A role in hypertension? J Hypertens. 28:1261–1272. 2010.PubMed/NCBI
16	Wolinsky H: Long-term effects of hypertension on the rat aortic wall and their relation to concurrent aging changes. Morphological and chemical studies. Circ Res. 30:301–309. 1972. View Article : Google Scholar : PubMed/NCBI
17	Wang Y, Zhang J, Gao H, Zhao S, Ji X, Liu X, You B, Li X and Qiu J: Profilin-1 promotes the development of hypertension-induced artery remodeling. J Histochem Cytochem. 62:298–310. 2014. View Article : Google Scholar : PubMed/NCBI
18	Safar M, Chamiot-Clerc P, Dagher G and Renaud JF: Pulse pressure, endothelium function, and arterial stiffness in spontaneously hypertensive rats. Hypertension. 38:1416–1421. 2001. View Article : Google Scholar : PubMed/NCBI
19	Chan YH, Yiu KH, Lau KK, Yiu YF, Li SW, Lam TH, Lau CP, Siu CW and Tse HF: The CHADS2 and CHA2DS2-VASc scores predict adverse vascular function, ischemic stroke and cardiovascular death in high-risk patients without atrial fibrillation: Role of incorporating PR prolongation. Atherosclerosis. 237:504–513. 2014. View Article : Google Scholar : PubMed/NCBI
20	Tanaka M, Ishii H, Aoyama T, Takahashi H, Toriyama T, Kasuga H, Takeshita K, Yoshikawa D, Amano T and Murohara T: Ankle brachial pressure index but not brachial-ankle pulse wave velocity is a strong predictor of systemic atherosclerotic morbidity and mortality in patients on maintenance hemodialysis. Atherosclerosis. 219:643–647. 2011. View Article : Google Scholar : PubMed/NCBI
21	Ng K, Butlin M and Avolio AP: Persistent effect of early, brief angiotensin-converting enzyme inhibition on segmental pressure dependency of aortic stiffness in spontaneously hypertensive rats. J Hypertens. 30:1782–1790. 2012. View Article : Google Scholar : PubMed/NCBI
22	Rudic RD and Sessa WC: Nitric oxide in endothelial dysfunction and vascular remodeling: Clinical correlates and experimental links. Am J Hum Genet. 64:673–677. 1999. View Article : Google Scholar : PubMed/NCBI
23	Fujita K, Matsumura Y, Kita S, Miyazaki Y, Hisaki K, Takaoka M and Morimoto S: Role of endothelin-1 and the ETA receptor in the maintenance of deoxycorticosterone acetate-salt-induced hypertension. Br J Pharmacol. 114:925–930. 1995. View Article : Google Scholar : PubMed/NCBI
24	Statsenko ME and Derevianchenko MV: Correction of endothelial dysfunction in hypertensive patients with type II diabetes mellitus during combined antihypertensive therapy. Ter Arkh. 86:90–93. 2014.In Russian.
25	Zhu WW, Liu XP, Wu N, Zhao TT, Zhao Y, Zhang J and Shao JH: Beneficial effects of losartan on vascular injury induced by advanced glycosylation end products and their receptors in spontaneous hypertension rats. Mol Cell Biochem. 304:35–43. 2007. View Article : Google Scholar : PubMed/NCBI
26	Jalili T, Carlstrom J, Kim S, Freeman D, Jin H, Wu TC, Litwin SE and David Symons J: Quercetin-supplemented diets lower blood pressure and attenuate cardiac hypertrophy in rats with aortic constriction. J Cardiovasc Pharmacol. 47:531–541. 2006. View Article : Google Scholar : PubMed/NCBI
27	Boghdady NA: Antioxidant and antiapoptotic effects of proanthocyanidin and ginkgo biloba extract against doxorubicin-induced cardiac injury in rats. Cell Biochem Funct. 31:344–351. 2013. View Article : Google Scholar
28	Ozkan G, Ulusoy S, Alkanat M, Orem A, Akcan B, Ersöz S, Yuluğ E, Kaynar K and Al S: Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A-induced cardiotoxicity. Ren Fail. 34:460–466. 2012. View Article : Google Scholar : PubMed/NCBI
29	Shao ZH, Wojcik KR, Dossumbekova A, Hsu C, Mehendale SR, Li CQ, Qin Y, Sharp WW, Chang WT, Hamann KJ, et al: Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling. J Cell Biochem. 107:697–705. 2009. View Article : Google Scholar : PubMed/NCBI
30	Belcaro G, Ledda A, Hu S, Cesarone MR, Feragalli B and Dugall M: Grape seed procyanidins in pre- and mild hypertension: A registry study. Evid Based Complement Alternat Med. 2013:3131422013. View Article : Google Scholar : PubMed/NCBI
31	Yu BP: Cellular defenses against damage from reactive oxygen species. Physiol Rev. 74:139–162. 1994.PubMed/NCBI
32	González J, Valls N, Brito R and Rodrigo R: Essential hypertension and oxidative stress: New insights. World J Cardiol. 6:353–366. 2014. View Article : Google Scholar : PubMed/NCBI
33	Matés JM and Sánchez-Jiménez F: Antioxidant enzymes and their implications in pathophysiologic processes. Front Biosci. 4:D339–D345. 1999. View Article : Google Scholar : PubMed/NCBI
34	Zheng H and Yu YS: Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats. Biochem Pharmacol. 83:1269–1277. 2012. View Article : Google Scholar : PubMed/NCBI
35	Ulker S, McMaster D, McKeown PP and Bayraktutan U: Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation. Cardiovasc Res. 59:488–500. 2003. View Article : Google Scholar : PubMed/NCBI