Nutr Res Pract.  2017 Oct;11(5):388-395. 10.4162/nrp.2017.11.5.388.

Antihypertensive effect of Ganjang (traditional Korean soy sauce) on Sprague-Dawley Rats

Affiliations
  • 1Department of Food Science and Human Nutrition, Chonbuk National University, 567, Baekje-daero, Duckjin-gu, Jeonju, Jeonbuk 54896, Korea. cha8@jbnu.ac.kr

Abstract

BACKGROUND/OBJECTIVES
Although Korean fermented foods contain large amounts of salt, which is known to exacerbate health problems, these foods still have beneficial effects such as anti-hypertension, anti-cancer, and anti-colitis properties. We hypothesized that ganjang may have different effects on blood pressure compared to same concentrations of salt.
MATERIALS/METHODS
Sprague-Dawley rats were divided into control (CT), NaCl (NC), and ganjang (GJ) groups and orally administered with 8% NaCl concentration for 9 weeks. The systolic blood pressure (SBP), serum chemistry, Na⁺ and K⁺ concentrations and renal gene expressions were measured.
RESULTS
The SBP was significantly increased in the NC group compared to the GJ and CT groups. In addition, the Na+ concentration in urine was higher in the GJ and NC groups than the CT group, but the urine volume was increased in the GJ group compared to the other groups. The serum renin levels were decreased in the GJ group compared to the CT group, while the serum aldosterone level was decreased in the GJ group relative to the NC group. The mRNA expression of the renin, angiotensin II type I receptor, and mineralocorticoid receptor were significantly lower in the GJ group compared to other groups. Furthermore, GJ group showed the lowest levels of genes for Na⁺ transporter in kidney cortex such as Na⁺/K⁺ ATPaseα1 (NKAα1), Na⁺/H⁺ exchanger 3 (NHE3), Na⁺/HCO₃⁻ co-exchanger (NBC), and carbonic anhydrases II (CAII).
CONCLUSIONS
The decreased SBP in the GJ could be due to decreased renin and aldosterone levels in serum and increased urinary volume and excretion of Na⁺ with its transporter gene alteration. Therefore, ganjang may have antihypertensive effect despite its high contents of salt.

Keyword

Ganjang; dietary salt; hypertension; renin-angiotensin-aldosterone system; traditional Korean soy sauce

MeSH Terms

Aldosterone
Angiotensin II
Blood Pressure
Carbonic Anhydrases
Chemistry
Gene Expression
Hypertension
Kidney Cortex
Rats, Sprague-Dawley*
Receptors, Mineralocorticoid
Renin
Renin-Angiotensin System
RNA, Messenger
Aldosterone
Angiotensin II
Carbonic Anhydrases
RNA, Messenger
Receptors, Mineralocorticoid
Renin

Figure

  • Fig. 1 Manufacturing process diagram for ganjang

  • Fig. 2 Systolic blood pressure for experimental period. Points are mean ± SD (n = 8). Values with different letters indicate statistical difference (P < 0.05) by Duncan's multiple range test (a > b). CT, Control; NC, NaCl group; GJ, ganjang group.

  • Fig. 3 Renin, angiotensin II, and aldosterone level in serum. Values are shown as the means ± SD. Values with different letters within a column are significantly different from each other at P < 0.05 by Duncan's multiple range test (a > b). CT, Control; NC, NaCl group; GJ, ganjang group.

  • Fig. 4 RASS relative gene expression in kidney cortex. Values are shown as the means ± SD. Values with different letters within a column are significantly different from each other at P < 0.05 by Duncan's multiple range test (a > b > c). CT, Control; NC, NaCl group; GJ, ganjang group. ACE, angiotensin converting enzyme; AT1 receptor, angiotensin II type 1 receptor; MR, mineralocorticoid receptor.

  • Fig. 5 Sodiumtransporter gene expression in kidney cortex. Values are shown as the means ± SD. Values with different letters within a column are significantly different from each other at P < 0.05 by Duncan's multiple range test (a > b > c). CT, Control; NC, NaCl group; GJ, ganjang group. NKAα1, Na+/K+ ATPaseα1; NBC, Na+/HCO3- co-exchanger; CAII, carbonic anhydrases II; NHE3, Na+/H+ exchanger 3; NCX, Na+/Ca2+ exchanger.

  • Fig. 6 Diagram of the effect of ganjang compared to table salt. When compared to table salt intake, renin and aldosterone secretion was decreased with ganjang. MR, NKAα1, NBC, NHE3, and CAII mRNA were also decreased, indicating a decrease of Na+ reabsorption. Therefore, the results from this study showed that the probability of hypertension is lower in a diet including ganjang compared to a high-salt diet, evident by down regulation of sodium transporters in the GJ group compared to the NC group. CT, Control; NC, NaCl group; GJ, ganjang group; ACE, angiotensin converting enzyme; AT1 receptor, angiotensin II type 1 receptor; MR, mineralcorticoid receptor; NKAα1, Na+/K+ ATPaseα1; NBC, Na+/HCO3- co-exchanger; NHE3, Na+/H+ exchanger 3; CAII, carbonic anhydrases II; NCX, Na+/Ca2+ exchanger.


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Reference

1. Poulter NR, Prabhakaran D, Caulfield M. Hypertension. Lancet. 2015; 386:801–812.
Article
2. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute. National High Blood Pressure Education Program Coordinating Committee. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003; 42:1206–1252.
Article
3. Schunkert H, Ingelfinger JR, Hirsch AT, Pinto Y, Remme WJ, Jacob H, Dzau VJ. Feedback regulation of angiotensin converting enzyme activity and mRNA levels by angiotensin II. Circ Res. 1993; 72:312–318.
Article
4. Trepiccione F, Zacchia M, Capasso G. The role of the kidney in salt-sensitive hypertension. Clin Exp Nephrol. 2012; 16:68–72.
Article
5. de Wardener HE, He FJ, MacGregor GA. Plasma sodium and hypertension. Kidney Int. 2004; 66:2454–2466.
Article
6. Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA. Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev. 2005; 85:679–715.
Article
7. Song JL, Choi JH, Seo JH, Lim YI, Park KY. Anti-colitic effects of kanjangs (fermented soy sauce and sesame sauce) in dextran sulfate sodium-induced colitis in mice. J Med Food. 2014; 17:1027–1035.
Article
8. Lee HJ, Lee KW, Kim KH, Kim HK, Lee HJ. Antitumor activity of peptide fraction from traditional Korean soy sauce. J Microbiol Biotechnol. 2004; 14:628–630.
9. Matsui T, Zhu XL, Shiraishi K, Ueki T, Noda Y, Matsumoto K. Antihypertensive effect of salt-free soy sauce, a new fermented seasoning, in spontaneously hypertensive rats. J Food Sci. 2010; 75:H129–H134.
Article
10. Nakahara T, Sugimoto K, Sano A, Yamaguchi H, Katayama H, Uchida R. Antihypertensive mechanism of a peptide-enriched soy sauce-like seasoning: the active constituents and its suppressive effect on renin-angiotensin-aldosterone system. J Food Sci. 2011; 76:H201–H206.
Article
11. Maia DR, Lopes KL, mann JC, Furukawa LN. High maternal sodium intake alters sex-specific renal renin-angiotensin system components in newborn Wistar offspring. J Dev Orig Health Dis. Forthcoming 2016.
Article
12. Lei GT, Wu QH. Effects of oxidative stress and gender differences in SD rats with high-salt hypertension via acute short-term cold exposure. Heart. 2010; 96:A40.
13. Korkmaz D. Precipitation titration: “Determination of Chloride by the Mohr Method”. Methods. 2001; 2:1–6.
14. Rhee MY, Kim JH, Na SH, Chung JW, Bae JH, Nah DY, Gu N, Kim HY. Elevation of heart-femoral pulse wave velocity by short-term low sodium diet followed by high sodium diet in hypertensive patients with sodium sensitivity. Nutr Res Pract. 2016; 10:288–293.
Article
15. Gu JW, Young E, Pan ZJ, Tucker KB, Shparago M, Huang M, Bailey AP. Long-term high salt diet causes hypertension and alters renal cytokine gene expression profiles in Sprague-Dawley rats. Beijing Da Xue Xue Bao. 2009; 41:505–515.
16. Song HJ, Park SJ, Jang DJ, Kwon DY, Lee HJ. High consumption of salt-fermented vegetables and hypertension risk in adults: a 12-year follow-up study. Asia Pac J Clin Nutr. 2017; 26:698–707.
17. Alauddin M, Shirakawa H, Koseki T, Kijima N, Ardiansyah , Budijanto S, Islam J, Goto T, Komai M. Fermented rice bran supplementation mitigates metabolic syndrome in stroke-prone spontaneously hypertensive rats. BMC Complement Altern Med. 2016; 16:442.
Article
18. Kho MC, Lee YJ, Park JH, Kim HY, Yoon JJ, Ahn YM, Tan R, Park MC, Cha JD, Choi KM, Kang DG, Lee HS. Fermented red ginseng potentiates improvement of metabolic dysfunction in metabolic syndrome rat models. Nutrients. 2016; 8:E369.
Article
19. Yahya MA, Alhaj OA, Al-Khalifah AS. Antihypertensive effect of fermented skim camel (Camelus dromedarius) milk on spontaneously hypertensive rats. Nutr Hosp. 2017; 34:416–421.
Article
20. Beltrán-Barrientos LM, Hernández-Mendoza A, Torres-Llanez MJ, González-Córdova AF, Vallejo-Córdoba B. Invited review: fermented milk as antihypertensive functional food. J Dairy Sci. 2016; 99:4099–4110.
Article
21. Geleijnse JM, Kok FJ, Grobbee DE. Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials. J Hum Hypertens. 2003; 17:471–480.
Article
22. Féraille E, Doucet A. Sodium-potassium-adenosinetriphosphatase-dependent sodium transport in the kidney: hormonal control. Physiol Rev. 2001; 81:345–418.
Article
23. Iwamoto T, Kita S, Zhang J, Blaustein MP, Arai Y, Yoshida S, Wakimoto K, Komuro I, Katsuragi T. Salt-sensitive hypertension is triggered by Ca2+ entry via Na+/Ca2+ exchanger type-1 in vascular smooth muscle. Nat Med. 2004; 10:1193–1199.
Article
24. Iwamoto T. Vascular Na+/Ca2+ exchanger: implications for the pathogenesis and therapy of salt-dependent hypertension. Am J Physiol Regul Integr Comp Physiol. 2006; 290:R536–R545.
25. Huang F, Yu P, Yuan Y, Li Q, Lin F, Gao Z, Chen F, Zhu P. The relationship between sodium excretion and blood pressure, urine albumin, central retinal arteriolar equivalent. BMC Cardiovasc Disord. 2016; 16:194.
Article
26. Shao W, Seth DM, Prieto MC, Kobori H, Navar LG. Activation of the renin-angiotensin system by a low-salt diet does not augment intratubular angiotensinogen and angiotensin II in rats. Am J Physiol Renal Physiol. 2013; 304:F505–F514.
Article
27. Ichihara A, Kaneshiro Y, Takemitsu T, Sakoda M, Itoh H. The (pro) renin receptor and the kidney. Semin Nephrol. 2007; 27:524–528.
28. Schricker K, Holmer S, Hamann M, Riegger G, Kurtz A. Interrelation between renin mRNA levels, renin secretion, and blood pressure in two-kidney, one clip rats. Hypertension. 1994; 24:157–162.
Article
29. Tank JE, Henrich WL, Moe OW. Regulation of glomerular and proximal tubule renin mRNA by chronic changes in dietary NaCl. Am J Physiol. 1997; 273:F892–F898.
30. Mazzocchi G, Gottardo G, Macchi V, Malendowicz LK, Nussdorfer GG. The AT2 receptor-mediated stimulation of adrenal catecholamine release may potentiate the AT1 receptor-mediated aldosterone secretagogue action of angiotensin-II in rats. Endocr Res. 1998; 24:17–28.
Article
31. Tsai CF, Yang SF, Chu HJ, Ueng KC. Cross-talk between mineralocorticoid receptor/angiotensin II type 1 receptor and mitogen-activated protein kinase pathways underlies aldosterone-induced atrial fibrotic responses in HL-1 cardiomyocytes. Int J Cardiol. 2013; 169:17–28.
Article
32. Thomas W, McEneaney V, Harvey BJ. Aldosterone-induced signalling and cation transport in the distal nephron. Steroids. 2008; 73:979–984.
Article
33. Jaffe IZ, Mendelsohn ME. Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res. 2005; 96:643–650.
Article
34. Yang BC, Phillips MI, Mohuczy D, Meng H, Shen L, Mehta P, Mehta JL. Increased angiotensin II type 1 receptor expression in hypercholesterolemic atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol. 1998; 18:1433–1439.
Article
35. Han F, Ding J, Shi Y. Expression of amygdala mineralocorticoid receptor and glucocorticoid receptor in the single-prolonged stress rats. BMC Neurosci. 2014; 15:77.
Article
36. Dixit MP, Xu L, Xu H, Bai L, Collins JF, Ghishan FK. Effect of angiotensin-II on renal Na+/H+ exchanger-NHE3 and NHE2. Biochim Biophys Acta. 2004; 1664:38–44.
Article
37. Marsigliante S, Muscella A, Elia MG, Greco S, Storelli C. Angiotensin II AT1 receptor stimulates Na+ -K+ATPase activity through a pathway involving PKC-ζ in rat thyroid cells. J Physiol. 2003; 546:461–470.
Article
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