Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Paterna, Valencia, Spain.
Unidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe, Universidad de Valencia, Valencia, Spain.
Life Sci. 2017 Oct 1;186:118-124. doi: 10.1016/j.lfs.2017.07.036. Epub 2017 Aug 8.
Bovine lactoferrin (LF) hydrolysates and peptides identified thereof have shown antihypertensive effects in rat models, mainly but not exclusively by angiotensin-converting enzyme inhibition. In this study we aimed to assess the vasoactive effects and mechanisms of an ultrafiltered (<3kDa) pepsin LF hydrolysate (LFH) and a heptapeptide identified in a LF hydrolysate produced by yeast proteolysis (DPYKLRP) in peripheral resistance arteries from spontaneously hypertensive rats (SHRs).
We used a myograph system for isometric tension recording in isolated small mesenteric arteries from SHRs. Direct vasoactive effects of LFH (30-100μg/mL) and DPYKLRP (30-100μM) were assessed in arteries precontracted with phenylephrine (PE, 10μM) or KCl (120mM), and in PE-precontracted arteries preincubated (10min) with the NO synthase inhibitor L-NAME (0.1mM) or the cyclooxygenase inhibitor indomethacin (10μM). Indirect vasoactive effects of LFH (30-100μg/mL) or DPYKLRP (30-100μM) preincubation (10min) on the relaxant responses to the NO donor sodium nitroprusside (SNP, 0.01-10μM) or acetylcholine (Ach, 1-100μM) were also studied in PE-precontracted arteries.
Both LHF and DPYKLRP elicited direct relaxation of mesenteric arteries, by a mechanism involving NO release, counteracting modulation by prostanoids and K efflux. Moreover, LF-derived peptides also showed indirect vasoactive effects by enhancing endothelium-dependent relaxation to Ach and endothelium-independent relaxation to SNP.
In conclusion, LF-derived peptides show ex vivodirect and indirect relaxing effects in small mesenteric arteries from SHRs. These vasoactive effects would reduce vascular peripheral resistance in vivo, and thus contribute to their antihypertensive effects.
牛乳铁蛋白（LF）水解物及其鉴定的肽在大鼠模型中表现出降压作用，主要但不仅限于血管紧张素转换酶抑制作用。在这项研究中，我们旨在评估超滤液（<3kDa）胃蛋白酶 LF 水解物（LFH）和酵母蛋白水解产生的 LF 水解物中鉴定的七肽（DPYKLRP）对自发性高血压大鼠（SHR）外周阻力动脉的血管活性作用及其机制。
我们使用离体肠系膜小动脉肌描记系统进行等长张力记录。在预先用苯肾上腺素（PE，10μM）或氯化钾（120mM）预收缩的血管中，评估 LFH（30-100μg/mL）和 DPYKLRP（30-100μM）的直接血管活性作用，以及在预先用一氧化氮合酶抑制剂 L-NAME（0.1mM）或环氧化酶抑制剂吲哚美辛（10μM）孵育 10min 的 PE 预收缩血管中。还研究了 LFH（30-100μg/mL）或 DPYKLRP（30-100μM）预孵育（10min）对 PE 预收缩血管中一氧化氮供体硝普钠（SNP，0.01-10μM）或乙酰胆碱（Ach，1-100μM）的松弛反应的间接血管活性作用。
LFH 和 DPYKLRP 均引起肠系膜动脉的直接松弛作用，其机制涉及一氧化氮的释放，对抗前列腺素和钾外流的调节。此外，LF 衍生的肽还通过增强内皮依赖性对 Ach 的松弛作用和内皮非依赖性对 SNP 的松弛作用表现出间接的血管活性作用。
LF 衍生的肽在 SHR 的小肠系膜动脉中表现出体外直接和间接的舒张作用。这些血管活性作用可降低体内血管外周阻力，从而有助于其降压作用。
