Siltari A, Roivanen J, Korpela R, Vapaatalo H
University of Helsinki, Faculty of Medicine, Department of Pharmacology, Helsinki, Finland.
Metropolia University of Applied Sciences, Helsinki, Finland.
J Physiol Pharmacol. 2017 Jun;68(3):407-418.
Bradykinin is the main player of the kallikrein-kinin system. Bradykinin-induced vasodilatation is age-dependent; this is believed to be associated with the level of expression of the two bradykinin receptors (BR1 and BR2) in the vasculature. The aim of this study was to clarify bradykinin-induced vascular reactivity of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) after 6 weeks' consumption of a drink containing bioactive tripeptides (Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro). Two age groups were used: young (10 weeks at the end of experiment) and old (24 weeks). Blood pressure was monitored weekly by the tail-cuff method. After six weeks, vascular reactivity was assessed in vitro in mesenteric artery rings focusing on bradykinin induced activity. Blood pressure was lowered in old SHR after 6 weeks' tripeptide consumption compared to water drinking controls (P < 0.05). Blood pressure was lowered by peptide consumption also in old WKY (P < 0.05) but tripeptide consumption exerted no effect on the blood pressure of young animals. Old SHR suffered from endothelial and smooth muscle dysfunction which was not improved by these tripeptides. Interestingly, bradykinin caused vasoconstriction even in young SHR; this was blocked by a non-selective cyclooxygenase (COX) inhibitor but not by a B1 and B2 receptor antagonist. The expressions of mRNA of COX-1 and COX-2 in aorta were slightly upregulated in old SHR. ACE-1 activity in aorta and protein level in kidney, but not ACE-1 mRNA expression was upregulated in old animals (P < 0.05). To conclude, long-term feeding with a drink containing tripeptides lowers or prevents the age-associated increase in blood pressure in hypertensive and normotensive animals. ACE-1 activity, protein level but not mRNA expression are elevated in old animals. We also demonstrated that the vascular inflammation and dysfunction present in aged hypertensive animals cause bradykinin to induce vasoconstriction; this is not prevented by tripeptide feeding but involves the prostaglandin pathway.
缓激肽是激肽释放酶-激肽系统的主要作用因子。缓激肽诱导的血管舒张具有年龄依赖性；这被认为与血管中两种缓激肽受体（BR1和BR2）的表达水平有关。本研究的目的是阐明在饮用含生物活性三肽（异亮氨酸-脯氨酸-脯氨酸、缬氨酸-脯氨酸-脯氨酸和亮氨酸-脯氨酸-脯氨酸）的饮料6周后，自发性高血压大鼠（SHR）和年龄匹配的Wistar-Kyoto大鼠（WKY）的缓激肽诱导的血管反应性。使用了两个年龄组：年轻组（实验结束时10周龄）和老年组（24周龄）。每周通过尾套法监测血压。六周后，在体外评估肠系膜动脉环中以缓激肽诱导活性为重点的血管反应性。与饮用自来水的对照组相比，老年SHR饮用三肽6周后血压降低（P<0.05）。老年WKY饮用肽后血压也降低（P<0.05），但三肽饮用对年轻动物的血压没有影响。老年SHR存在内皮和平滑肌功能障碍，这些三肽并未改善。有趣的是，缓激肽即使在年轻SHR中也会引起血管收缩；这被非选择性环氧化酶（COX）抑制剂阻断，但未被B1和B2受体拮抗剂阻断。老年SHR主动脉中COX-1和COX-2的mRNA表达略有上调。老年动物主动脉中的ACE-1活性和肾脏中的蛋白水平上调，但ACE-1 mRNA表达未上调（P<0.05）。总之，长期饮用含三肽的饮料可降低或预防高血压和正常血压动物中与年龄相关的血压升高。老年动物中ACE-1活性、蛋白水平升高，但mRNA表达未升高。我们还证明，老年高血压动物中存在的血管炎症和功能障碍导致缓激肽诱导血管收缩；这不能通过三肽喂养预防，但涉及前列腺素途径。
