The Protective Effect Of Grape Seed Proanthocyanidin Extract (GSPE) On Arterial Remodeling In Spontaneous Hypertensive Rats

Background and ObjectiveEssential hypertension is one of the most common cardiovascular disease and is also considered the most important risk factor for the occurrence of cardiovascular mortality disease. Hypertension has a serious impairment on target organs, ultimately leading to the failure of them, which has bad effect on life health. Therefore, the target organ protection in patients with high blood pressure is the key to the treatment of hypertension. The present study has shown that arterial remodeling is closely related to target organs damage caused by hypertension. So it has important clinical significance for the treatment of arterial remodeling caused by hypertension. With the in-depth study of arterial remodeling, we found that the pathogenesis mechanisms of arterial remodeling are complicated and not yet fully elucidated. A large amount of evidence shows that oxidative stress plays a central role in its pathophysiology. Grape seed proanthocyanidin extract (GSPE) is a combination of biologically active polyphenolic flavonoids, contains oligomeric proanthocyanidins, which have demonstrated a marked spectrum of biological activities such as antioxidant, anti-inflammatory, anti-allergic, anti-mutagenic, anti-cancer, anti-aging. Recently, GSPE has been reported to show a protective effect on cardiac injury caused by Oxidative stress. Therefore, we hypothesize that GSPE might attenuate hypertension-induced arterial remodeling by repressing oxidative stress. The present study was to evaluate the protective effect GSPE of on arterial remodeling in hypertensive rats.MethodsTwenty-week-old male spontaneous hypertensive rats (SHRs, n=20) and Wistar-Kyoto rats (WKYs, n=10) were randomly assigned to three groups (n=10 per group):(1) Control group WKY-C group) (WKY control rats treated with 1 ml of 0.9% nitric sodium orally) (2) Model group (SHR-C group) (SHR control rats treated with 1 ml of 0.9% nitric sodium orally) (3) GSPE group (SHR-T) (SHRs treated with GSPE at a dosage of 250 mg/kg·d). The animals were subjected to drug administration as described above by oral gavage for 22 weeks. Body Weight, Systolic Blood pressure (SBP) and Pulse Wave Velocity (PWV) of three groups was observed. Morphological changes in thoracic aortas were quantified with hematoxylin-eosin (HE) or sirius red-victoria blue staining. 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) and activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT).Results1.GSPE has no significantly effect on Body weigh and Systolic blood pressure (SBP). During the 22 weeks of treatment, body weight among the three groups has no differences (P>0.05). Compared with Control group, SBP was significantly increased in both the Model and the GSPE groups (P＜0.01), while SBP in the Model and the GSPE groups has no difference (P>0.05).2.GSPE decreases pulse wave velocity. Compared with the control group, PWV was significantly increased in Model group and GSPE group (P<0.01) and PWV was significantly decreased in GSPE group in comparison with Model group (P<0.05).3.GSPE ameliorates the change in arterial remodeling. Morphological observation showed the increased in wall thickness (WT) (P＜0.01), inner diameter (ID) (P<0.05) and Wall thickness:inner diameter(WT/ID) (P<0.05) in Model group in comparison with Control group. Following administration of GSPE, morphological observation showed the decreased in wall thickness (WT) (P＜0.01), WT/ID (P＜0.05), while inner diameter (ID) has no difference between both group (P>0.05). As hematoxylin-eosin or sirius red-victoria blue shown, the aortic wall in the Model group rats was thickened, with hyperplastic collagen fibers in the media and with decreased, disordered and even ruptured elastic fibers. However, the aortic elastic fibers in the GSPE group were fairly ordered.4.GSPE preserves ultrastructural changes of the thoracic aorta. In the Model group, the repeatedly repaired basement membrane had a worm-eaten appearance, and the internal elastic lamina was split, with abundant extracellular matrix content intertwined with the basement membrane. Moreover, fibroblast-like cells showed in the subendothelium, and the apoptosis of endothelial cells was observed in die Model group. The administration of GSPE tended to improve the preservation of the fine structure of the basement membrane and internal elastic lamina and to decrease the number of inserted fibroblast-like cells in the subendothelium.5. GSPE significantly improves endothelial function. The content of NO in the thoracic aorta in the Model group decreased significantly (P＜0.01), while GSPE treatment increased NO production when comparing the GSPE group with the Model group (P<0.01). However, ET-1 expression increased greatly in the Model group in comparison to that in the Control group (P<0.01), which was capable of being reversed by GSPE treatment (P＜0.01).6. GSPE decreased the level of oxidative stress. Compared with the Control group, SOD and CAT activities were decreased (P<0.01), while MDA expression was higher in the aorta tissue of the Model group (P<0.01). After the GSPE treatment, the levels of SOD and CAT were increased (P<0.01) and MDA expression was higher (P＜0.05).Conclusion1.Arterial remodeling happened in the aorta tissue of SHRs.2. Arterial remodeling of SHRs was accompanied with the imbalance of oxidant and antioxidant system and endothelial dysfunction.3. GSPE could attenuate hypertension-induced arterial remodeling by repressing oxidative stress.