Skip to main content

Advertisement

Log in

Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats.

Methods

Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting.

Results

Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05).

Conclusion

KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Matthews KA, Crawford SL, Chae CU, Everson-Rose SA, Sowers MF, Sternfeld B, et al. Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition? J Am Coll Cardiol 2009;54:2366–2373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kannel WB. Metabolic risk factors for coronary heart disease in women: perspective from the Framingham Study. Am Heart J 1987;114:413–419.

    Article  CAS  PubMed  Google Scholar 

  3. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365:217–223.

    Article  PubMed  Google Scholar 

  4. Ramezani Tehrani F, Bahri M, Gholami R, Hashemi S, Nakhoda K, Azizi F. Secular trend of menopausal age and related factors among Tehrani women born from 1930 to 1960: Tehran Lipid and Glucose Study. Arch Iran Med 2014;17:406–410.

    PubMed  Google Scholar 

  5. Lim HS, Kim TH, Lee HH, Park YH, Kim JM, Lee BR. Hypertension and age at onset of natural menopause in Korean postmenopausal women: results from the Korea National Health and Nutrition Examination Survey (2008–2013). Maturitas 2016;90:17–23.

    Article  PubMed  Google Scholar 

  6. Yanes LL, Romero DG, Iliescu R, Zhang H, Davis D, Reckelhoff JF. Postmenopausal hypertension: role of the renin-angiotensin system. Hypertension 2010;56:359–363.

    Article  CAS  PubMed  Google Scholar 

  7. Dobarro D, Gómez-Rubín MC, Sanchez-Recalde A, Moreno R, Galeote G, Jimenez-Valero S, et al. Current pharmacological approach to restore endothelial dysfunction. Cardiovasc Hematol Agents Med Chem 2009;7:212–222.

    Article  CAS  PubMed  Google Scholar 

  8. Langrish JP, Mills NL, Bath LE, Warner P, Webb DJ, Kelnar CJ, et al. Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure. Hypertension 2009;53:805–811.

    Article  CAS  PubMed  Google Scholar 

  9. Mercuro G, Zoncu S, Saiu F, Mascia M, Melis GB, Rosano GM. Menopause induced by oophorectomy reveals a role of ovarian estrogen on the maintenance of pressure homeostasis. Maturitas 2004;47:131–138.

    Article  CAS  PubMed  Google Scholar 

  10. Pu D, Tan R, Yu Q, Wu J. Metabolic syndrome in menopause and associated factors: a meta-analysis. Climacteric 2017;20:583–591.

    Article  CAS  PubMed  Google Scholar 

  11. Fung MM, Poddar S, Bettencourt R, Jassal SK, Barrett-Connor E. A cross-sectional and 10-year prospective study of postmenopausal estrogen therapy and blood pressure, renal function, and albuminuria: the Rancho Bernardo Study. Menopause 2011;18:629–637.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sun AJ, Wang YP, Gu B, Zheng TP, Lin SQ, Bai WP, et al. A multi-center, randomized, controlled and open clinical trial of Heyan Kuntai Capsule and hormone therapy in perimenopausal women. Chin J Integr Med (Chin) 2018;24:487–493.

    Article  Google Scholar 

  13. Zhang JJ, Fang L, Shi LY, Lai ZW, Lu ZY, Xiong JQ, et al. Protective effects and mechanisms investigation of Kuntai Capsule on the ovarian function of a novel model with accelerated aging ovaries. J Ethnopharmacol 2017;195:173–181.

    Article  PubMed  Google Scholar 

  14. Pollow DP, Romero-Aleshire MJ, Sanchez JN, Konhilas JP, Brooks HL. Ang II-induced hypertension in the VCD mouse model of menopause is prevented by estrogen replacement during perimenopause. Am J Physiol Regulat Integr Comparat Physiol 2015;309:R1546–R1552.

    Article  CAS  Google Scholar 

  15. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart disease and stroke statistics—2018 update: a report from the American Heart Association. Circulation 2018;137:e467–e492.

    Article  Google Scholar 

  16. Coylewright M, Reckelhoff JF, Ouyang P. Menopause and hypertension: an age-old debate. Hypertension 2008;51:952–959.

    Article  CAS  PubMed  Google Scholar 

  17. Matrai M, Hetthéssy JR, Nadasy GL, Szekacs B, Mericli M, Acs N, et al. Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension. Menopause 2016;23:778–783.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Huang Z, Han Z, Ye B, Dai Z, Shan P, Lu Z, et al. Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes. Eur J Pharmacol 2015;762:1–10.

    Article  CAS  PubMed  Google Scholar 

  19. Yu L, Li Q, Yu B, Yang Y, Jin Z, Duan W, et al. Berberine attenuates myocardial ischemia/reperfusion injury by reducing oxidative stress and inflammation response: role of silent information regulator 1. Oxid Med Cell Longev 2016;2016:1689602.

    Article  PubMed  Google Scholar 

  20. Gasiorowski K, Lamer-Zarawska E, Leszek J, Parvathaneni K, Yendluri BB, Blach-Olszewska Z, et al. Flavones from root of Scutellaria baicalensis Georgi: drugs of the future in neurodegeneration? CNS Neurol Disord Drug Targets 2011;10:184–191.

    Article  CAS  PubMed  Google Scholar 

  21. Guzik TJ, Touyz RM. Oxidative stress, inflammation, and vascular aging in hypertension. Hypertension 2017;70:660–667.

    Article  CAS  PubMed  Google Scholar 

  22. Dinh QN, Drummond GR, Sobey CG, Chrissobolis S. Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. Biomed Res Int 2014;2014:406960.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Egler RA, Fernandes E, Rothermund K, Sereika S, de Souza-Pinto N, Jaruga P, et al. Regulation of reactive oxygen species, DNA damage, and c-Myc function by peroxiredoxin 1. Oncogene 2005;24:8038–8050.

    Article  CAS  PubMed  Google Scholar 

  24. Wei X, Zhu X, Hu N, Zhang X, Sun T, Xu J, et al. Baicalin attenuates angiotensin II-induced endothelial dysfunction. Biochem Biophys Res Commun 2015;465:101–107.

    Article  CAS  PubMed  Google Scholar 

  25. Androulakis ES, Tousoulis D, Papageorgiou N, Tsioufis C, Kallikazaros I, Stefanadis C. Essential hypertension: is there a role for inflammatory mechanisms? Cardiol Rev 2009;17:216–221.

    Article  PubMed  Google Scholar 

  26. Ren J, Taegtmeyer H. Too much or not enough of a good thing—the Janus faces of autophagy in cardiac fuel and protein homeostasis. J Mol Cell Cardiol 2015;84:223–226.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Ge XF contributed to study design, experimental research and manuscript draft. Li SS and Yang X contributed to study design and data analysis. Liu YH and Lu MQ contributed to animal experiments. Su HN contributed to molecular experiments. Sun XW contributed to manuscript draft. All authors read and approved the final version.

Corresponding author

Correspondence to Xin Yang.

Additional information

Conflicts of Interest

The authors declare that they have no conflict of interest.

Supported by 2020 Bethune Excellent Talent Training Program for Young and Middle-Aged Doctors

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ge, Xf., Li, Ss., Liu, Yh. et al. Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats. Chin. J. Integr. Med. 29, 526–533 (2023). https://doi.org/10.1007/s11655-022-3514-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-022-3514-3

Keywords

Navigation