Abstract
Purpose
Vinegar has been reported to lower blood pressure, but its mechanism is unclear. This study explored whether vinegar plays antihypertensive effect by activating AMP-activated protein kinase (AMPK) pathway.
Methods
Male spontaneously hypertensive rats (SHRs) were assigned to vinegar, acetic acid, nifedipine, nifedipine + vinegar, or distilled water by oral gavage for 8 weeks. Blood and aortas were analyzed for biochemical indices and protein expression levels. Sv40-transformed aortic rat endothelia cell line (SVAREC) cells were treated with acetate at different doses for 24 h; protein expression levels were assessed.
Results
Vinegar and acetic acid decreased blood pressure in SHRs on weeks 6 and 8, and nifedipine + vinegar had a better effect on blood pressure control than vinegar or nifedipine alone. Vinegar and acetic acid could decrease serum renin and angiotensin-converting enzyme (ACE) activities, angiotensin II and aldosterone concentrations in SHRs. Vinegar and acetic acid also increased AMP/ATP ratios and expression levels of pAMPK, PPARγ coactivator-1α (PGC-1α), and PPARγ while inhibited angiotensin II type 1 receptor (AT1R) expression in SHRs. The changes in these protein expressions were also found in SVAREC cells treated with 200 or 400 μmol/L acetate. In the presence of AMPK inhibitor or PGC-1α small interfering RNA, the effects of acetate on their downstream protein expression in SVAREC cells were abolished, respectively.
Conclusion
Vinegar activates AMPK by increasing AMP/ATP ratios, thereby increases PGC-1α and PPARγ expressions, and inhibits AT1R expression in SHRs. Acetic acid is responsible for the antihypertensive effects of vinegar. There is a joint effect between vinegar and nifedipine in blood pressure control.
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References
Kearney PM, Whelton M, Reynolds K et al (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365:217–223
Krzesinski JM, Saint-Remy A (2012) Essential hypertension, a complex trait. Rev Med Liege 67:279–285
Leibowitz A, Faltin Z, Perl A et al (2014) Red grape berry-cultured cells reduce blood pressure in rats with metabolic-like syndrome. Eur J Nutr 53:973–980
Girgih AT, Alashi A, He R et al (2014) Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats. Eur J Nutr 53:1237–1246
Kondo S, Tayama K, Tsukamoto Y et al (2001) Antihypertensive effects of acetic acid and vinegar on spontaneously hypertensive rats. Biosci Biotechnol Biochem 65:2690–2694
Sakakibara S, Murakami R, Takahashi M et al (2010) Vinegar intake enhances flow-mediated vasodilatation via upregulation of endothelial nitric oxide synthase activity. Biosci Biotechnol Biochem 74:1055–1061
Honsho S, Sugiyama A, Takahara A et al (2005) A red wine vinegar beverage can inhibit the renin-angiotensin system: experimental evidence in vivo. Biol Pharm Bull 28:1208–1210
Takahara A, Sugiyama A, Honsho S et al (2005) The endothelium-dependent vasodilator action of a new beverage made of red wine vinegar and grape juice. Biol Pharm Bull 28:754–756
John M (2007) ACEIs, ARBs, or DRI for adults with hypertension. Comparative effectiveness review summary guides for clinicians [Internet]. Rockville (MD) (2011): Agency for healthcare research and quality (US); 2007-.AHRQ comparative effectiveness reviews
Herichova I, Szantoova K (2013) Renin-angiotensin system: upgrade of recent knowledge and perspectives. Endocr Regul 47:39–52
Bokarev IN, Matvienko EV (2013) Modern approaches to the treatment of primary arterial hypertension. Klin Med (Mosk) 91:4–8
Ketsawatsomkron P, Pelham CJ, Groh S et al (2010) Does peroxisome proliferator-activated receptor-gamma (PPAR gamma) protect from hypertension directly through effects in the vasculature? J Biol Chem 285:9311–9316
Diep QN, El Mabrouk M, Cohn JS et al (2002) Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferator-activated receptor-gamma. Circulation 105:2296–2302
Imayama I, Ichiki T, Inanaga K et al (2006) Telmisartan downregulates angiotensin II type 1 receptor through activation of peroxisome proliferator-activated receptor gamma. Cardiovasc Res 72:184–190
Burns KA, Vanden Heuvel JP (2007) Modulation of PPAR activity via phosphorylation. Biochim Biophys Acta 1771:952–960
Yamashita H, Maruta H, Jozuka M et al (2009) Effects of acetate on lipid metabolism in muscles and adipose tissues of type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biosci Biotechnol Biochem 73:570–576
Cao LQ, Chen XL, Wang Q et al (2007) Upregulation of PTEN involved in rosiglitazone-induced apoptosis in human hepatocellular carcinoma cells. Acta Pharmacol Sin 28:879–887
Entani E, Asai M, Tsujihata S et al (1998) Antibacterial action of vinegar against food-borne pathogenic bacteria including Escherichia coli O157:H7. J Food Prot 61:953–959
Fushimi T, Suruga K, Oshima Y et al (2006) Dietary acetic acid reduces serum cholesterol and triacylglycerols in rats fed a cholesterol-rich diet. Br J Nutr 95:916–924
Shishehbor F, Mansoori A, Sarkaki AR et al (2008) Apple cider vinegar attenuates lipid profile in normal and diabetic rats. Pak J Biol Sci 11:2634–2638
Johnston CS, Kim CM, Buller AJ (2004) Vinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with insulin resistance or type 2 diabetes. Diabetes Care 27:281–282
Ostman E, Granfeldt Y, Persson L et al (2005) Vinegar supplementation lowers glucose and insulin responses and increases satiety after a bread meal in healthy subjects. Eur J Clin Nutr 59:983–988
Johnston CS, White AM, Kent SM (2009) Preliminary evidence that regular vinegar ingestion favorably influences hemoglobin A1c values in individuals with type 2 diabetes mellitus. Diabetes Res Clin Pract 84:e15–e17
Kishi M, Fukaya M, Tsukamoto Y et al (1999) Enhancing effect of dietary vinegar on the intestinal absorption of calcium in ovariectomized rats. Biosci Biotechnol Biochem 63:905–910
Fushimi T, Tayama K, Fukaya M et al (2001) Acetic acid feeding enhances glycogen repletion in liver and skeletal muscle of rats. J Nutr 131:1973–1977
Zhao XL, Chen J, Cui YL et al (2006) Current status of primary hypertension in China: an epidemiological study of 12 provinces, 1 autonomous regions, and 1 municipality. Zhonghua Yi Xue Za Zhi 86:1148–1152
Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24:78–90
Puigserver P, Wu Z, Park CW et al (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839
Yamashita H, Kaneyuki T, Tagawa K (2001) Production of acetate in the liver and its utilization in peripheral tissues. Biochim Biophys Acta 1532:79–87
Mallat SG, Itani HS, Tanios BY (2013) Current perspectives on combination therapy in the management of hypertension. Integr Blood Press Control 6:69–78
Taira N (2006) Nifedipine: a novel vasodilator. Drugs 66:1–3
Acknowledgments
This study was supported by the National Natural Science Foundation of China (No. 81202188, 81202191), 12th China Five-Year Scientific and Technical Plan (No. 2012BAI02B00), Postdoctoral Science Foundation (No. 2013T60393), Wu Liande foundation of Harbin Medical University (WLD-QN1406), and the Key Lab Found from the Department of Education of Heilongjiang Province (YYKFKT1210).
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The authors declare that they have no conflict of interest.
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Lixin Na and Xia Chu contributed equally to this work.
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Na, L., Chu, X., Jiang, S. et al. Vinegar decreases blood pressure by down-regulating AT1R expression via the AMPK/PGC-1α/PPARγ pathway in spontaneously hypertensive rats. Eur J Nutr 55, 1245–1253 (2016). https://doi.org/10.1007/s00394-015-0937-7
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DOI: https://doi.org/10.1007/s00394-015-0937-7