Department of Human Nutritional Sciences and The Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2.
J Agric Food Chem. 2011 Sep 28;59(18):9854-60. doi: 10.1021/jf201911p. Epub 2011 Sep 2.
The blood pressure lowering effect of a pea protein hydrolysate (PPH) that contained <3 kDa peptides, isolated by membrane ultrafiltration from the thermolysin digest of pea protein isolate (PPI), was examined using different rat models of hypertension as well as hypertensive human subjects. The PPH showed weak in vitro activities against renin and angiotensin converting enzyme (ACE) with inhibitory activities of 17 and 19%, respectively, at 1 mg/mL test concentration. Oral administration of the PPH to spontaneously hypertensive rats (SHR) at doses of 100 and 200 mg/kg body weight led to a lowering of hourly systolic blood pressure (SBP), with a maximum reduction of 19 mmHg at 4 h. In contrast, orally administered unhydrolyzed PPI had no blood pressure reducing effect in SHR, suggesting that thermolysin hydrolysis may have been responsible for releasing bioactive peptides from the native protein. Oral administration of the PPH to the Han:SPRD-cy rat (a model of chronic kidney disease) over an 8-week period led to 29 and 25 mmHg reductions in SBP and diastolic blood pressure, respectively. The PPH-fed rats had lower plasma levels of angiotensin II, the major vasopressor involved in development of hypertension, but there was no effect on plasma activity or renal mRNA levels of ACE. However, renal expression of renin mRNA levels was reduced by approximately 50% in the PPH-fed rats, suggesting that reduced renin may be responsible for the reduced levels of angiotensin II. In a 3-week randomized double blind placebo-controlled crossover human intervention trial (7 volunteers), significant (p<0.05) reductions (over placebo) in SBP of 5 and 6 mmHg were obtained in the second and third weeks, respectively, for the PPH group. Therefore, thermolysin derived bioactive peptides from PPH reduced blood pressure in hypertensive rats and human subjects, likely via effects on the renal angiotensin system.
一种豌豆蛋白水解产物（PPH）的降压作用，该产物通过膜超滤从豌豆蛋白分离物（PPI）的胰蛋白酶消化物中分离出来，<3 kDa 的肽，具有弱的体外抑制活力肾素和血管紧张素转换酶（ACE），在 1mg/ml 测试浓度下，分别抑制 17%和 19%。PPH 以 100 和 200mg/kg 体重的剂量口服给予自发性高血压大鼠（SHR），导致每小时收缩压（SBP）降低，4 小时最大降低 19mmHg。相比之下，口服未水解的 PPI 对 SHR 没有降低血压的作用，这表明胰蛋白酶水解可能负责从天然蛋白中释放生物活性肽。在 8 周的时间里，给 Han:SPRD-cy 大鼠（一种慢性肾病模型）口服 PPH，分别使 SBP 和舒张压降低 29 和 25mmHg。PPH 喂养的大鼠血浆血管紧张素 II 水平降低，血管紧张素 II 是参与高血压发展的主要升压物质，但对血浆 ACE 活性或肾 mRNA 水平没有影响。然而，PPH 喂养的大鼠肾素 mRNA 水平降低了约 50%，这表明肾素的减少可能是导致血管紧张素 II 水平降低的原因。在一项为期 3 周的随机双盲安慰剂对照交叉人体干预试验（7 名志愿者）中，与安慰剂组相比，PPH 组在第二和第三周的收缩压分别显著（p<0.05）降低了 5mmHg 和 6mmHg。因此，源自 PPH 的胰蛋白酶衍生的生物活性肽可降低高血压大鼠和人类的血压，可能通过对肾脏血管紧张素系统的影响。
