Ile-Pro-Pro attenuates sympathetic activity and hypertension.
Angiotensin-converting enzyme
Antihypertension
Sympathetic activity
Tripeptide
Vascular remodeling
Journal
Journal of physiology and biochemistry
ISSN: 1877-8755
Titre abrégé: J Physiol Biochem
Pays: Spain
ID NLM: 9812509
Informations de publication
Date de publication:
15 Jul 2024
15 Jul 2024
Historique:
received:
21
03
2024
accepted:
05
07
2024
medline:
15
7
2024
pubmed:
15
7
2024
entrez:
15
7
2024
Statut:
aheadofprint
Résumé
Isoleucine-proline-proline (Ile-Pro-Pro, IPP) is a natural food source tripeptide that inhibits angiotensin-converting enzyme (ACE) activity. The aim of this study was to determine the central and peripheral roles of IPP in attenuating sympathetic activity, oxidative stress and hypertension. Male Sprague-Dawley rats were subjected to sham-operated surgery (Sham) or two-kidney one-clip (2K1C) surgery to induce renovascular hypertension. Renal sympathetic nerve activity and blood pressure were recorded. Bilateral microinjections of IPP to hypothalamic paraventricular nucleus (PVN) attenuated sympathetic activity (-16.1 ± 2.5%, P < 0.001) and hypertension (-8.7 ± 1.5 mmHg, P < 0.01) in 2K1C rats by inhibiting ACE activity and subsequent angiotensin II and superoxide production in the PVN. Intravenous injections of IPP also attenuated sympathetic activity (-15.1 ± 2.1%, P < 0.001) and hypertension (-16.8 ± 2.3 mmHg, P < 0.001) via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. The duration of the effects of the intravenous IPP was longer than those of the PVN microinjection, but the sympatho-inhibitory effect of intravenous injections occurred later than that of the PVN microinjection. Intraperitoneal injection of IPP (400 pmol/day for 20 days) attenuated hypertension and vascular remodeling via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. These results indicate that IPP attenuates hypertension and sympathetic activity by inhibiting ACE activity and oxidative stress. The sympathoinhibitory effect of peripheral IPP is mainly caused by the ACE inhibition in PVN, and the antihypertensive effect is related to the sympathoinhibition and the arterial ACE inhibition. Long-term intraperitoneal IPP therapy attenuates hypertension, oxidative stress and vascular remodeling.
Identifiants
pubmed: 39008241
doi: 10.1007/s13105-024-01034-x
pii: 10.1007/s13105-024-01034-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 32071106 & 31871148
Informations de copyright
© 2024. The Author(s) under exclusive licence to University of Navarra.
Références
Nakamura Y, Yamamoto N, Sakai K, Okubo A, Yamazaki S, Takano T (1995) Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. J Dairy Sci 78:777–783
doi: 10.3168/jds.S0022-0302(95)76689-9
pubmed: 7790570
Nourmohammadi E, Mahoonak AS (2018) Health implications of bioactive peptides: a review. Int J Vitam Nutr Res 88:319–343
doi: 10.1024/0300-9831/a000418
pubmed: 31140388
Li S, Bu T, Zheng J, Liu L, He G, Wu J (2019) Preparation, Bioavailability, and mechanism of emerging activities of ile-pro-pro and Val-Pro-Pro. Compr Rev Food Sci Food Saf 18:1097–1110
doi: 10.1111/1541-4337.12457
pubmed: 33337010
Gregory KS, Cozier GE, Schwager SLU, Sturrock ED, Acharya KR (2024) Structural insights into the inhibitory mechanism of angiotensin-I-converting enzyme by the lactotripeptides IPP and VPP. FEBS Lett 598:242–251
doi: 10.1002/1873-3468.14768
pubmed: 37904282
Craft IL, Geddes D, Hyde CW, Wise IJ, Matthews DM (1968) Absorption and malabsorption of glycine and glycine peptides in man. Gut 9:425–437
doi: 10.1136/gut.9.4.425
pubmed: 5677277
pmcid: 1552714
Vanhoof G, Goossens F, De M, Hendriks I, Scharpe D S (1995) Proline motifs in peptides and their biological processing. FASEB J 9:736–744
doi: 10.1096/fasebj.9.9.7601338
pubmed: 7601338
Iwasa M, Takezoe S, Kitaura N, Sutani T, Miyazaki H, Aoi W (2021) A milk casein hydrolysate-derived peptide enhances glucose uptake through the AMP-activated protein kinase signalling pathway in skeletal muscle cells. Exp Physiol 106:496–505
doi: 10.1113/EP088770
pubmed: 33369793
Khalid DM, Gleeson JP, Brayden DJ, Byrne HJ, Frias JM, Ryan SM (2022) Formulation, characterisation and evaluation of the antihypertensive peptides, isoleucine-proline-proline and Leucine-Lysine-Proline in Chitosan Nanoparticles Coated with Zein for oral drug delivery. Int J Mol Sci 23:11160
doi: 10.3390/ijms231911160
van der Pijl PC, Kies AK, Ten Have GA, Duchateau GS, Deutz NE (2008) Pharmacokinetics of proline-rich tripeptides in the pig. Peptides 29:2196–2202
doi: 10.1016/j.peptides.2008.08.011
pubmed: 18789987
Ahmad H, Khan H, Haque S, Ahmad S, Srivastava N, Khan A (2023) Angiotensin-Converting Enzyme and Hypertension: A Systemic Analysis of Various ACE Inhibitors, Their Side Effects, and Bioactive Peptides as a Putative Therapy for Hypertension. J Renin Angiotensin Aldosterone Syst 2023:7890188
Nguyen Dinh CA, Montezano AC, Burger D, Touyz RM (2013) Angiotensin II, NADPH oxidase, and redox signaling in the vasculature. Antioxid Redox Signal 19:1110–1120
doi: 10.1089/ars.2012.4641
Alcocer LA, Bryce A, De Padua BD, Lara J, Cortes JM, Quesada D, Rodriguez P (2023) The pivotal role of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in Hypertension Management and Cardiovascular and Renal Protection: a critical Appraisal and comparison of International guidelines. Am J Cardiovasc Drugs 23:663–682
doi: 10.1007/s40256-023-00605-5
pubmed: 37668854
pmcid: 10625506
Grassi G, Mark A, Esler M (2015) The sympathetic nervous system alterations in human hypertension. Circ Res 116:976–990
doi: 10.1161/CIRCRESAHA.116.303604
pubmed: 25767284
pmcid: 4367954
DeLalio LJ, Sved AF, Stocker SD (2020) Sympathetic nervous system contributions to hypertension: updates and therapeutic relevance. Can J Cardiol 36:712–720
doi: 10.1016/j.cjca.2020.03.003
pubmed: 32389344
Dampney RA, Michelini LC, Li DP, Pan HL (2018) Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular nucleus in normotensive and hypertensive states. Am J Physiol Heart Circ Physiol 315:H1200–H1214
doi: 10.1152/ajpheart.00216.2018
pubmed: 30095973
pmcid: 6297824
Chen WW, Xiong XQ, Chen Q, Li YH, Kang YM, Zhu GQ (2015) Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension. Acta Physiol (Oxf) 213:778–794
doi: 10.1111/apha.12447
pubmed: 25598170
Chen AD, Zhang SJ, Yuan N, Xu Y, De W, Gao XY, Zhu GQ (2011) AT
doi: 10.1113/expphysiol.2010.054353
pubmed: 21097645
Ye C, Qiu Y, Zhang F, Chen AD, Zhou H, Wang JJ, Chen Q, Li YH, Kang YM, Zhu GQ (2020) Chemical stimulation of renal tissue induces sympathetic activation and pressor response via hypothalamic paraventricular nucleus. Neurosci Bull 36:143–152
doi: 10.1007/s12264-019-00417-1
pubmed: 31392556
Wu LL, Zhang Y, Li XZ, Du XL, Gao Y, Wang JX, Wang XL, Chen Q, Li YH, Zhu GQ, Tan X (2022) Impact of selective renal afferent denervation on oxidative stress and vascular remodeling in spontaneously hypertensive rats. Antioxid (Basel) 11:1003
doi: 10.3390/antiox11051003
Fan ZD, Zhang L, Shi Z, Gan XB, Gao XY, Zhu GQ (2012) Artificial microRNA interference targeting AT1a receptors in paraventricular nucleus attenuates hypertension in rats. Gene Ther 19:810–817
doi: 10.1038/gt.2011.145
pubmed: 21956687
Liu L, Zheng J, Zhou M, Li S, He G, Wu J (2021) Peptide analogues of VPP and IPP with improved glucose uptake activity in L6 myotubes can be released from cereal proteins. J Agric Food Chem 69:2875–2883
doi: 10.1021/acs.jafc.1c00587
pubmed: 33645989
Zimmerman MC (2011) Angiotensin II and angiotensin-1-7 redox signaling in the central nervous system. Curr Opin Pharmacol 11:138–143
doi: 10.1016/j.coph.2011.01.001
pubmed: 21257347
pmcid: 3075313
Sipola M, Finckenberg P, Korpela R, Vapaatalo H, Nurminen ML (2002) Effect of long-term intake of milk products on blood pressure in hypertensive rats. J Dairy Res 69:103–111
doi: 10.1017/S002202990100526X
pubmed: 12047101
Imamura A, Mackenzie HS, Lacy ER, Hutchison FN, Fitzgibbon WR, Ploth DW (1995) Effects of chronic treatment with angiotensin converting enzyme inhibitor or an angiotensin receptor antagonist in two-kidney, one-clip hypertensive rats. Kidney Int 47:1394–1402
doi: 10.1038/ki.1995.196
pubmed: 7637269
Ren XS, Tong Y, Qiu Y, Ye C, Wu N, Xiong XQ, Wang JJ, Han Y, Zhou YB, Zhang F, Sun HJ, Gao XY, Chen Q, Li YH, Kang YM, Zhu GQ (2020) MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression. J Extracell Vesicles 9:1698795
doi: 10.1080/20013078.2019.1698795
pubmed: 31839907
Tanaka M, Dohgu S, Komabayashi G, Kiyohara H, Takata F, Kataoka Y, Nirasawa T, Maebuchi M, Matsui T (2019) Brain-transportable dipeptides across the blood-brain barrier in mice. Sci Rep 9:5769
doi: 10.1038/s41598-019-42099-9
pubmed: 30962462
pmcid: 6453885
Chen J, Zhuang Y, Zhang Y, Liao H, Liu R, Cheng J, Zhang Z, Sun J, Gao J, Wang X, Chen S, Zhang L, Che F, Wan Q (2022) A synthetic BBB-permeable tripeptide GCF confers neuroprotection by increasing glycine in the ischemic brain. Front Pharmacol 13:950376
doi: 10.3389/fphar.2022.950376
pubmed: 36046828
pmcid: 9420865
Setiadi A, Korim WS, Elsaafien K, Yao ST (2018) The role of the blood-brain barrier in hypertension. Exp Physiol 103:337–342
doi: 10.1113/EP086434
pubmed: 28986948
Biancardi VC, Son SJ, Ahmadi S, Filosa JA, Stern JE (2014) Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier. Hypertension 63:572–579
doi: 10.1161/HYPERTENSIONAHA.113.01743
pubmed: 24343120
Hirooka Y (2020) Sympathetic activation in hypertension: importance of the Central Nervous System. Am J Hypertens 33:914–926
doi: 10.1093/ajh/hpaa074
pubmed: 32374869
Ye C, Zheng F, Zhu WN, Li GQ XZ (2022) Extracellular vesicles in vascular remodeling. Acta Pharmacol Sin 43:2191–2201
doi: 10.1038/s41401-021-00846-7
pubmed: 35022541
pmcid: 9433397
Pacurari M, Kafoury R, Tchounwou PB, Ndebele K (2014) The Renin-Angiotensin-aldosterone system in vascular inflammation and remodeling. Int J Inflam 2014:689360