Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
PLoS One. 2013 Nov 29;8(11):e82829. doi: 10.1371/journal.pone.0082829. eCollection 2013.
There is a growing interest in using functional food components as therapy for cardiovascular diseases such as hypertension. We have previously characterized a tri-peptide IRW (Ile-Arg-Trp) from egg white protein ovotransferrin; this peptide showed anti-inflammatory, anti-oxidant and angiotensin converting enzyme (ACE) inhibitor properties in vitro. Given the pathogenic roles played by angiotensin, oxidative stress and inflammation in the spontaneously hypertensive rat (SHR), we tested the therapeutic potential of IRW in this well-established model of hypertension.
16-17 week old male SHRs were orally administered IRW at either a low dose (3 mg/Kg BW) or a high dose (15 mg/Kg BW) daily for 18 days. Blood pressure (BP) and heart rate were measured by telemetry. Animals were sacrificed at the end of the treatment for vascular function studies and measuring markers of inflammation. IRW treatment attenuated mean BP by ~10 mmHg and ~40 mmHg at the low- and high-dose groups respectively compared to untreated SHRs. Heart rate was not affected. Reduction in BP was accompanied by the restoration of diurnal variations in BP, preservation of nitric oxide dependent vasorelaxation, as well as reduction of plasma angiotensin II, other inflammatory markers and tissue fibrosis.
Our results demonstrate anti-hypertensive effects of IRW in vivo likely mediated through ACE inhibition, endothelial nitric oxide synthase and anti-inflammatory properties.
人们对利用功能性食品成分作为治疗心血管疾病(如高血压)的方法越来越感兴趣。我们之前从卵转铁蛋白中鉴定了一种三肽 IRW(异亮氨酸-精氨酸-色氨酸);该肽在体外具有抗炎、抗氧化和血管紧张素转换酶(ACE)抑制作用。鉴于血管紧张素、氧化应激和炎症在自发性高血压大鼠(SHR)中发挥的致病作用,我们在该高血压的成熟模型中测试了 IRW 的治疗潜力。
16-17 周龄雄性 SHR 每天经口给予低剂量(3mg/Kg BW)或高剂量(15mg/Kg BW)IRW 治疗 18 天。通过遥测法测量血压(BP)和心率。治疗结束时,处死动物进行血管功能研究和炎症标志物测量。与未治疗的 SHR 相比,IRW 治疗分别使低剂量和高剂量组的平均血压降低约 10mmHg 和 40mmHg。心率不受影响。BP 的降低伴随着 BP 昼夜节律的恢复,一氧化氮依赖性血管舒张的维持,以及血浆血管紧张素 II、其他炎症标志物和组织纤维化的减少。
我们的结果表明,IRW 在体内具有抗高血压作用,可能通过 ACE 抑制、内皮型一氧化氮合酶和抗炎特性介导。