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Open Access

Antihypertensive effects of whey protein hydrolysate involve reshaping the gut microbiome in spontaneously hypertension rats

Peipei Doua, Xiaoyi Lia, Xiaoxiao Zoua, Kai Wanga, Lei Yaob, Zhuo Sunb, Hui Honga, Yongkang Luoa, Yuqing Tana( )
Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
Hebei Dongkang Dairy Co., Ltd., Shijiazhuang 052160, China

Peer review under responsibility of Tsinghua University Press.

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Abstract

Novel angiotensin-converting enzyme (ACE) inhibitory peptides were identified from whey protein hydrolysates (WPH) in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study. Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension. WPH inhibited ACE activity (20.81%, P < 0.01), and reduced renin concentration (P < 0.05), thereby reducing systolic blood pressure (SBP) (12.63%, P < 0.05) in spontaneously hypertensive rats. The increased Akkermansia, Bacteroides, and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention. These changes jointly contributed to low blood pressure. The heart weight and cardiomyocyte injuries (hypertrophy and degeneration) were alleviated by WPH. The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated (Wnt) signaling pathway and Apelin signaling pathway were altered after WPH supplementation. Notably, WPH alleviated serum oxidative stress, indicated by the decreased malondialdehyde content (P < 0.01), enhanced total antioxidant capacity (P < 0.01) and superoxide dismutase activity (P < 0.01). The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements.

Keywords

Whey protein hydrolysateAntihypertensionShort chain fatty acidsGut microbiome

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References

[1]

M. Yildiz, A.A. Oktay, M.H. Stewart, et al., Left ventricular hypertrophy and hypertension, Prog. Cardiovasc. Dis. 63 (2020) 10-21. https://doi.org/10.1016/j.pcad.2019.11.009.
Crossref Google Scholar
[2]

A. Verma, S.D. Solomon, Diastolic dysfunction as a link between hypertension and heart failure, Med. Clin. N. Am. 93 (2009) 647-664. https://doi.org/10.1016/j.mcna.2009.02.013.
Crossref Google Scholar
[3]

P.M. Kearney, M. Whelton, K. Reynolds, et al., Global burden of hypertension: analysis of worldwide data, The Lancet 365 (2005) 217-223. https://doi.org/10.1016/S0140-6736(05)17741-1.
Crossref Google Scholar
[4]

C. Wang, Y. Yuan, M.Y. Zheng, et al., Association of age of onset of hypertension with cardiovascular diseases and mortality, J. Am. Coll. Cardiol. 75 (2020) 2921-2930. https://doi.org/10.1016/j.jacc.2020.04.038.
Crossref Google Scholar
[5]

M. Volpe, A. Battistoni, D. Chin, et al., Renin as a biomarker of cardiovascular disease in clinical practice, Nutr. Metab. Cardiovasc. Dis. 22 (2012) 312-317. https://doi.org/10.1016/j.numecd.2011.12.006.
Crossref Google Scholar
[6]

A.R. Gunkel, K.H. Thurner, G. Kanonier, et al., Angioneurotic edema as a reaction to angiotensin-converting enzyme inhibitors, Am. J. Otolaryngol. 17 (1996) 87-91. https://doi.org/10.1016/S0196-0709(96)90001-0.
Crossref Google Scholar
[7]

T. Yang, M.M. Santisteban, V. Rodriguez, et al., Gut dysbiosis is linked to hypertension, Hypertension 65 (2015) 1331-1340. https://doi.org/10.1161/HYPERTENSIONAHA.115.05315.
Crossref Google Scholar
[8]

S. Adnan, J.W. Nelson, N.J. Ajami, et al., Alterations in the gut microbiota can elicit hypertension in rats, Physiol Genomics. 49 (2017) 96-104. https://doi.org/10.1152/physiolgenomics.00081.2016.
Crossref Google Scholar
[9]

M. Toral, I. Robles-Vera, N. de la Visitación, et al., Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats, Acta Physiol. 227 (2019) e13285. https://doi.org/10.1111/apha.13285.
Crossref Google Scholar
[10]

F. Yang, H.W. Chen, Y.H. Gao, et al., Gut microbiota-derived short-chain fatty acids and hypertension: mechanism and treatment, Biomed. Pharmacother. 130 (2020) 110503. https://doi.org/10.1016/j.biopha.2020.110503.
Crossref Google Scholar
[11]

S. Kim, R. Goel, A. Kumar, et al., Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure, Clin. Sci. 132 (2018) 701-718. https://doi.org/10.1042/CS20180087.
Crossref Google Scholar
[12]

J. Pluznick, A novel SCFA receptor, the microbiota, and blood pressure regulation, Gut Microbes. 5 (2014) 202-207. https://doi.org/10.4161/gmic.27492.
Crossref Google Scholar
[13]

F. Ndiaye, T. Vuong, J. Duarte, et al., Anti-oxidant, anti-inflammatory and immunomodulating properties of an enzymatic protein hydrolysate from yellow field pea seeds, Eur. J. Nutr. 51 (2012) 29-37. https://doi.org/10.1007/s00394-011-0186-3.
Crossref Google Scholar
[14]

A. Kaur, B.A. Kehinde, P. Sharma, et al., Recently isolated food-derived antihypertensive hydrolysates and peptides: a review, Food Chem. 346 (2021) 128719. https://doi.org/10.1016/j.foodchem.2020.128719.
Crossref Google Scholar
[15]

Y. Etemadian, V. Ghaemi, A.R. Shaviklo, et al., Development of animal/ plant-based protein hydrolysate and its application in food, feed and nutraceutical industries: state of the art, J. Clean. Prod. 278 (2021) 123219. https://doi.org/10.1016/j.jclepro.2020.123219.
Crossref Google Scholar
[16]

R. Vásquez-Villanueva, J.M. Orellana, M.L. Marina, et al., Isolation and characterization of angiotensin converting enzyme inhibitory peptides from peach seed hydrolysates: in vivo assessment of antihypertensive activity, J. Agric. Food Chem. 67 (2019) 10313-10320. https://doi.org/10.1021/acs.jafc.9b02213.
Crossref Google Scholar
[17]

F. Lin, L. Chen, R. Liang, et al., Pilot-scale production of low molecular weight peptides from corn wet milling byproducts and the antihypertensive effects in vivo and in vitro, Food Chem. 124 (2011) 801-807. https://doi.org/10.1016/j.foodchem.2010.06.099.
Crossref Google Scholar
[18]

S.J. Lee, Y.S. Kim, S.E. Kim, et al., Purification and characterization of a novel angiotensin I-converting enzyme inhibitory peptide derived from an enzymatic hydrolysate of duck skin byproducts, J. Agric. Food Chem. 60 (2012) 10035-10040. https://doi.org/10.1021/jf3023172.
Crossref Google Scholar
[19]

C. Zhang, Y.Q. Zhang, Z.Y. Wang, et al., Production and identification of antioxidant and angiotensin-converting enzyme inhibition and dipeptidyl peptidase Ⅳ inhibitory peptides from bighead carp (Hypophthalmichthys nobilis) muscle hydrolysate, J. Funct. Foods 35 (2017) 224-235. https://doi.org/10.1016/j.jff.2017.05.032.
Crossref Google Scholar
[20]

J.G. dos Santos Aguilar, H.H. Sato, Microbial proteases: production and application in obtaining protein hydrolysates, Food Res. Int. 103 (2018) 253-262. https://doi.org/10.1016/j.foodres.2017.10.044.
Crossref Google Scholar
[21]

A. Brandelli, D.J. Daroit, A.P.F. Corrêa, Whey as a source of peptides with remarkable biological activities, Food Res. Int. 73 (2015) 149-161. https://doi.org/10.1016/j.foodres.2015.01.016.
Crossref Google Scholar
[22]

F.S. Fajardo-Espinoza, C. Ordaz-Pichardo, U. Sankar, et al., In vitro cytomodulatory and immunomodulatory effects of bovine colostrum whey protein hydrolysates, Int. J. Food Sci. Technol. 56 (2021) 2109-2121. https://doi.org/10.1111/ijfs.14767.
Crossref Google Scholar
[23]

X.Y. Li, C.S. Feng, H. Hong, et al., Novel ACE inhibitory peptides derived from whey protein hydrolysates: identification and molecular docking analysis, Food Biosci. 48 (2022) 101737. https://doi.org/10.1016/j.fbio.2022.101737.
Crossref Google Scholar
[24]

E. Arranz, A.R. Corrochano, C. Shanahan, et al., Antioxidant activity and characterization of whey protein-based beverages: effect of shelf life and gastrointestinal transit on bioactivity, Innov. Food Sci. Emerg. 57 (2019) 102209. https://doi.org/10.1016/j.ifset.2019.102209.
Crossref Google Scholar
[25]

K. Wang, Z.X. Fu, X.Y. Li, et al., Whey protein hydrolysate alleviated atherosclerosis and hepatic steatosis by regulating lipid metabolism in apoE−/− mice fed a Western diet, Food Res. Int. 157 (2022) 111419. https://doi.org/10.1016/j.foodres.2022.111419.
Crossref Google Scholar
[26]
Food and Drug Adminstration, Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers 2005, Center for Drug Evaluation and Research (CDER) (2005) 1-27. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/estimating-maximum-safe-starting-dose-initial-clinical-trials-therapeutics-adult-healthy-volunteers.
[27]

K. Ishiguro, Y. Sameshima, T. Kume, et al., Hypotensive effect of a sweetpotato protein digest in spontaneously hypertensive rats and purification of angiotensin I-converting enzyme inhibitory peptides, Food Chem. 131 (2012) 774-779. https://doi.org/10.1016/j.foodchem.2011.09.038.
Crossref Google Scholar
[28]

R. He, Y.J. Wang, Y.J. Yang, et al., Rapeseed protein-derived ACE inhibitory peptides LY, RALP and GHS show antioxidant and anti-inflammatory effects on spontaneously hypertensive rats, J. Funct. Foods 55 (2019) 211-219. https://doi.org/10.1016/j.jff.2019.02.031.
Crossref Google Scholar
[29]

J. Chen, W. Duan, X. Ren, et al., Effect of foxtail millet protein hydrolysates on lowering blood pressure in spontaneously hypertensive rats, Eur. J. Nutr. 56 (2017) 2129-2138. https://doi.org/10.1007/s00394-016-1252-7.
Crossref Google Scholar
[30]

Q. Zhou, J. Wu, J. Tang, et al., Beneficial effect of higher dietary fiber intake on plasma HDL-C and TC/HDL-C ratio among Chinese rural-to-urban migrant workers, Int. J. Environ. Res. Public Health 12 (2015) 4726-4738. https://doi.org/10.3390/ijerph120504726.
Crossref Google Scholar
[31]

J.Y. Zhang, J. Yu, Y. Chen, et al., Exogenous hydrogen sulfide supplement attenuates isoproterenol-induced myocardial hypertrophy in a sirtuin 3-dependent manner, Oxid. Med. Cell. Longev. 2018 (2018) e9396089. https://doi.org/10.1155/2018/9396089.
Crossref Google Scholar
[32]

G. Matute-Bello, G. Downey, B.B. Moore, et al., An official American thoracic society workshop report: features and measurements of experimental acute lung injury in animals, Am. J. Respir. Cell Mol. Biol. 44 (2011) 725-738. https://doi.org/10.1165/rcmb.2009-0210ST.
Crossref Google Scholar
[33]

E.B. Selçuk, M. Sungu, H. Parlakpinar, et al., Evaluation of the cardiovascular effects of varenicline in rats, Drug Des. 9 (2015) 5705-5717. https://doi.org/10.2147/DDDT.S92268.
Crossref Google Scholar
[34]

Y.F. Liang, H.J. Zhang, L. Tian, et al., Gut microbiota and metabolic profile as affected by Maillard reaction products derived from bighead carp meat hydrolysates with galactose and galacto-oligosaccharides during in vitro pig fecal fermentation, Food Chem. 398 (2023) 133905. https://doi.org/10.1016/j.foodchem.2022.133905.
Crossref Google Scholar
[35]

S.S. Hu, C.H. Hu, L.Y. Luo, et al., Pu-erh tea increases the metabolite Cinnabarinic acid to improve circadian rhythm disorder-induced obesity, Food Chem. 394 (2022) 133500. https://doi.org/10.1016/j.foodchem.2022.133500.
Crossref Google Scholar
[36]

X. Wang, L. Wang, X. Cheng, et al., Hypertension-attenuating effect of whey protein hydrolysate on spontaneously hypertensive rats, Food Chem. 134 (2012) 122-126. https://doi.org/10.1016/j.foodchem.2012.02.074.
Crossref Google Scholar
[37]

O. Abdelhedi, M. Nasri, Basic and recent advances in marine antihypertensive peptides: production, structure-activity relationship and bioavailability, Trends Food Sci. Tech. 88 (2019) 543-557. https://doi.org/10.1016/j.tifs.2019.04.002.
Crossref Google Scholar
[38]

T. Yang, V. Aquino, G.O. Lobaton, et al., Sustained captopril-induced reduction in blood pressure is associated with alterations in gut-brain axis in the spontaneously hypertensive rat, J. Am. Heart Assoc. 8 (2019) e010721. https://doi.org/10.1161/JAHA.118.010721.
Crossref Google Scholar
[39]

B.S. Heran, M.M. Wong, I.K. Heran, et al., Blood pressure lowering efficacy of angiotensin converting enzyme (ACE) inhibitors for primary hypertension, Cochrane Db. Syst. Rev. 4 (2008). https://doi.org/10.1002/14651858.CD003823.pub2.
Crossref Google Scholar
[40]

O. Power, A. Fernández, R. Norris, et al., Selective enrichment of bioactive properties during ultrafiltration of a tryptic digest of β-lactoglobulin, J. Funct. Foods 9 (2014) 38-47. https://doi.org/10.1016/j.jff.2014.04.002.
Crossref Google Scholar
[41]

L.C. Pinheiro, J.E. Tanus-Santos, M.M. Castro, The potential of stimulating nitric oxide formation in the treatment of hypertension, Expert Opin. Ther. Targets 21 (2017) 543-556. https://doi.org/10.1080/14728222.2017.1310840.
Crossref Google Scholar
[42]

M.B. O’Keeffe, R.J. FitzGerald, Whey protein hydrolysate induced modulation of endothelial cell gene expression, J. Funct. Foods 40 (2018) 102-109. https://doi.org/10.1016/j.jff.2017.11.001.
Crossref Google Scholar
[43]

L. te Riet, J.H.M. van Esch, A.J.M. Roks, et al., Hypertension: renin-angiotensin-aldosterone system alterations, Circ. Res. 116 (2015) 960-975. https://doi.org/10.1161/CIRCRESAHA.116.303587.
Crossref Google Scholar
[44]

J. de Champlain, R. Wu, H. Girouard, et al., Oxidative stress in hypertension, Clin. Exp. Hypertens. A 26 (2004) 593-601. https://doi.org/10.1081/CEH-200031904.
Crossref Google Scholar
[45]

S. Sharma, G. Ruffenach, S. Umar, et al., Role of oxidized lipids in pulmonary arterial hypertension, Pulm. Circ. 6 (2016) 261-273. https://doi.org/10.1086/687293.
Crossref Google Scholar
[46]

S. Ogura, T. Shimosawa, Oxidative stress and organ damages, Curr. Hypertens. Rep. 16 (2014) 452. https://doi.org/10.1007/s11906-014-0452-x.
Crossref Google Scholar
[47]

X. Peng, Y.L. Xiong, B. Kong, Antioxidant activity of peptide fractions from whey protein hydrolysates as measured by electron spin resonance, Food Chem. 113 (2009) 196-201. https://doi.org/10.1016/j.foodchem.2008.07.068.
Crossref Google Scholar
[48]

X.C. Yu, Z. Li, X.R. Liu, et al., The antioxidant effects of whey protein peptide on learning and memory improvement in aging mice models, Nutrients 13 (2021) 2100. https://doi.org/10.3390/nu13062100.
Crossref Google Scholar
[49]

I. Saito, K. Yamagishi, Y. Kokubo, et al., Association of high-density lipoprotein cholesterol concentration with different types of stroke and coronary heart disease: The Japan Public Health Center-based prospective (JPHC) study, Atherosclerosis 265 (2017) 147-154. https://doi.org/10.1016/j.atherosclerosis.2017.08.032.
Crossref Google Scholar
[50]

D. Andrzejczak, D. Górska, The effects of celiprolol on serum concentrations of proinflammatory cytokines in hypertensive (SHR) and normotensive (WKY) rats, Pharmacol. Rep. 66 (2014) 68-73. https://doi.org/10.1016/j.pharep.2013.08.006.
Crossref Google Scholar
[51]

A. Mantovani, G. Zoppini, G. Targher, et al., Non-alcoholic fatty liver disease is independently associated with left ventricular hypertrophy in hypertensive type 2 diabetic individuals, J. Endocrinol. Invest. 35 (2012) 215-218. https://doi.org/10.1007/BF03345421.
Crossref Google Scholar
[52]

S.P. Cartland, N. Tamer, M.S. Patil, et al., A “Western Diet” promotes symptoms of hepatic steatosis in spontaneously hypertensive rats, Int. J. Exp. Pathol. 101 (2020) 152-161. https://doi.org/10.1111/iep.12369.
Crossref Google Scholar
[53]

R.J.F. Felizardo, I.K.M. Watanabe, P. Dardi, et al., The interplay among gut microbiota, hypertension and kidney diseases: the role of short-chain fatty acids, Pharmacol. Res. 141 (2019) 366-377. https://doi.org/10.1016/j.phrs.2019.01.019.
Crossref Google Scholar
[54]

J. De la Cuesta-Zuluaga, N.T. Mueller, R. Álvarez-Quintero, et al., Higher fecal short-chain fatty acid levels are associated with gut microbiome dysbiosis, obesity, hypertension and cardiometabolic disease risk factors, Nutrients 11 (2019) 51. https://doi.org/10.3390/nu11010051.
Crossref Google Scholar
[55]

F.Z. Marques, C.R. Mackay, D.M. Kaye, Beyond gut feelings: how the gut microbiota regulates blood pressure, Nat. Rev. Cardiol. 15 (2018) 20-32. https://doi.org/10.1038/nrcardio.2017.120.
Crossref Google Scholar
[56]

E.S. Chambers, T. Preston, G. Frost, et al., Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health, Curr. Nutr. Rep. 7 (2018) 198-206. https://doi.org/10.1007/s13668-018-0248-8.
Crossref Google Scholar
[57]

V. Karoor, D. Strassheim, T. Sullivan, et al., The short-chain fatty acid butyrate attenuates pulmonary vascular remodeling and inflammation in hypoxia-induced pulmonary hypertension, Int. J. Mol. Sci. 22 (2021) 9916. https://doi.org/10.3390/ijms22189916.
Crossref Google Scholar
[58]

H. Bartolomaeus, A. Balogh, M. Yakoub, et al., Short-chain fatty acid propionate protects from hypertensive cardiovascular damage, Circulation 139 (2019) 1407-1421. https://doi.org/10.1161/CIRCULATIONAHA.118.036652.
Crossref Google Scholar
[59]

M.S. Madhur, H.E. Lob, L.A. McCann, et al., Interleukin 17 promotes angiotensin Ⅱ-induced hypertension and vascular dysfunction, Hypertension 55 (2010) 500-507. https://doi.org/10.1161/HYPERTENSIONAHA.109.145094.
Crossref Google Scholar
[60]

I. Robles-Vera, M. Toral, J. Duarte, Microbiota and hypertension: role of the sympathetic nervous system and the immune system, Am. J. Hypertens. 33 (2020) 890-901. https://doi.org/10.1093/ajh/hpaa103.
Crossref Google Scholar
[61]

M. Luu, S. Pautz, V. Kohl, et al., The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes, Nat. Commun. 10 (2019) 760. https://doi.org/10.1038/s41467-019-08711-2.
Crossref Google Scholar
[62]

S. Ghosh, W. He, J. Gao, et al., Whole milk consumption is associated with lower risk of coronary artery calcification progression: evidences from the Multi-Ethnic Study of Atherosclerosis, Eur. J. Nutr. 60 (2021) 1049-1058. https://doi.org/10.1007/s00394-020-02301-5.
Crossref Google Scholar
[63]

M. Hecker, N. Sommer, H. Voigtmann, et al., Impact of short-and medium-chain fatty acids on mitochondrial function in severe inflammation, J. Parenter. Enteral Nutr. 38 (2014) 587-594. https://doi.org/10.1177/0148607113489833.
Crossref Google Scholar
[64]

P. Louis, H.J. Flint, Formation of propionate and butyrate by the human colonic microbiota, Environ. Microbiol. 19 (2017) 29-41. https://doi.org/10.1111/1462-2920.13589.
Crossref Google Scholar
[65]

J.L. Rico, K.F. Reardon, S.K. De Long, Inoculum microbiome composition impacts fatty acid product profile from cellulosic feedstock, Bioresour. 323 (2021) 124532. https://doi.org/10.1016/j.biortech.2020.124532.
Crossref Google Scholar
[66]

R.A. Corb Aron, A. Abid, C.M. Vesa, et al., Recognizing the benefits of pre-/probiotics in metabolic syndrome and type 2 diabetes mellitus considering the influence of Akkermansia muciniphila as a key gut bacterium, Microorganisms 9 (2021) 618. https://doi.org/10.3390/microorganisms9030618.
Crossref Google Scholar
[67]

H. Yu, L. Qin, H. Hu, et al., Alteration of the gut microbiota and its effect on AMPK/NADPH oxidase signaling pathway in 2K1C rats, Biomed. Res. Int. 2019 (2019) 8250619. https://doi.org/10.1155/2019/8250619.
Crossref Google Scholar
[68]

J. Li, F. Zhao, Y. Wang, et al., Gut microbiota dysbiosis contributes to the development of hypertension, Microbiome 5 (2017) 14. https://doi.org/10.1186/s40168-016-0222-x.
Crossref Google Scholar
[69]

M. Gómez-Guzmán, M. Toral, M. Romero, et al., Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats, Mol. Nutr. Food Res. 59 (2015) 2326-2336. https://doi.org/10.1002/mnfr.201500290.
Crossref Google Scholar
[70]

P. Malekar, M. Hagenmueller, A. Anyanwu, et al., Wnt signaling is critical for maladaptive cardiac hypertrophy and accelerates myocardial remodeling, Hypertension 55 (2010) 939-945. https://doi.org/10.1161/HYPERTENSIONAHA.109.141127.
Crossref Google Scholar
[71]

H.J. Chun, Z.A. Ali, Y. Kojima, et al., Apelin signaling antagonizes Ang Ⅱ effects in mouse models of atherosclerosis, J. Clin. Invest. 118 (2008) 3343-3354. https://doi.org/10.1172/JCI34871.
Crossref Google Scholar
[72]

H. Nguyen, V.L. Chiasson, P. Chatterjee, et al., Interleukin-17 causes Rho-kinase-mediated endothelial dysfunction and hypertension, Cardiovasc. Res. 97 (2013) 696-704. https://doi.org/10.1093/cvr/cvs422.
Crossref Google Scholar
[73]

A. Schäfer, J. Widder, M. Eigenthaler, et al., Reduced basal nitric oxide bioavailability and platelet activation in young spontaneously hypertensive rats, Biochem. Pharmacol. 67 (2004) 2273-2279. https://doi.org/10.1016/j.bcp.2004.02.034.
Crossref Google Scholar
[74]

T.D. Giles, Aspects of nitric oxide in health and disease: a focus on hypertension and cardiovascular disease, J. Clin. Hypertens. 8 (2006) 2-16. https://doi.org/10.1111/j.1524-6175.2006.06023.x.
Crossref Google Scholar
Food Science and Human Wellness
Volume 13 Issue 4,
July 2024
Pages 1974-1986
DOI: 10.26599/FSHW.2022.9250164
Cite this article:
Dou P, Li X, Zou X, et al. Antihypertensive effects of whey protein hydrolysate involve reshaping the gut microbiome in spontaneously hypertension rats. Food Science and Human Wellness, 2024, 13(4): 1974-1986. https://doi.org/10.26599/FSHW.2022.9250164

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Received: 04 October 2022
Revised: 05 November 2022
Accepted: 04 January 2023
Published: 20 May 2024
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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