Skip to main content

Advertisement

SpringerLink
Log in

TRPC6 participates in the development of blood pressure variability increase in sino-aortic denervated rats

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Increased blood pressure variability (BPV) has been proved to be associated with cardiovascular morbidity and mortality. It is of great significance to elucidate the mechanism of BPV increase. The cation channel transient receptor potential canonical 6 (TRPC6) is involved in a series of cardiovascular disease. Our experiment aimed to explore the role of TRPC6 in the development of BPV increase. Sino-aortic denervation (SAD) operation was applied to establish the model of BPV increase in rats. The BPV was presented as the standard deviation to the mean of systolic or diastolic blood pressure every 1 h during 12 h of the light period. SAD was performed in male Sprague Dawley (SD) rats at the age of 10 weeks. At 8 weeks after SAD operation, the hemodynamic parameters were determined non-invasively via a Rodent Blood Pressure Analysis System. The TRPC6 expressions in myocardial and thoracic aortic tissue was determined utilizing Western Blot, immunofluorescence and quantitative RT-PCR. The expression of TRPC3 was detected as well. To investigate whether TRPC6 was a causative factor of BPV increase in SAD rats, TRPC6 activator and inhibitor with three progressively increasing doses were intraperitoneally injected to the SAD rats. We found that SAD rats presented significant augmentation of systolic and diastolic BPV with no change of BP level and heart rate. The mRNA and protein expression levels of TRPC6 in myocardial and thoracic aortic tissue in SAD rats were substantially increased, but there was no obvious change in TRPC3 expression. The systolic and diastolic BPV increase were dose-dependently exacerbated after TRPC6 activation with GSK1702934A but were dose-dependently attenuated after TRPC6 inhibition with SAR7334. In Conclusion, the TRPC6 (but not TRPC3) expressions in myocardial and thoracic aortic tissue were substantially increased in SAD rats, and TRPC6 probably played an important role in the development of BPV elevation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Goldman MD, Min S, Lobo JM, Sohn MW (2020) Retrospective cohort study of the relationship between systolic blood pressure variability and multiple sclerosis disability. BMJ Open 10(2):e034355

    Article  PubMed  PubMed Central  Google Scholar 

  2. Stevens SL, Wood S, Koshiaris C, Law K, Glasziou P, Stevens RJ, McManus RJ (2016) Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. BMJ 354:i4098

    Article  PubMed  PubMed Central  Google Scholar 

  3. VARIABLE BRAIN consortium (2018) The association between blood pressure variability (BPV) with dementia and cognitive function: a systematic review and meta-analysis protocol. Syst Rev 7(1):163

    Article  Google Scholar 

  4. Miao CY, Xie HH, Zhan LS, Su DF (2006) Blood pressure variability is more important than blood pressure level in determination of end-organ damage in rats. J Hypertens 24(6):1125–1135

    Article  CAS  PubMed  Google Scholar 

  5. Parati G, Ochoa JE, Lombardi C, Bilo G (2013) Assessment and management of blood-pressure variability. Nat Rev Cardiol 10(3):143–155

    Article  PubMed  Google Scholar 

  6. Yano Y, Reis JP, Lewis CE, Sidney S, Pletcher MJ, Bibbins-Domingo K, Navar AM, Peterson ED, Bancks MP, Kanegae H, Gidding SS, Muntner P, Lloyd-Jones DM (2020) Association of blood pressure patterns in young adulthood with cardiovascular disease and mortality in middle age. JAMA Cardiol 5(4):382–389

    Article  PubMed  PubMed Central  Google Scholar 

  7. Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlöf B, Sever PS, Poulter NR (2010) Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. The Lancet 375(9718):895–905

    Article  Google Scholar 

  8. Seo SM, Chung WB, Choi IJ, Koh YS, Ihm SH, Kim PJ, Chung WS, Seung KB (2018) Visit-to-visit variability of systolic blood pressure predicts all-cause mortality in patients received percutaneous coronary intervention with drug-eluting stents. Heart Vessels 33(5):489–497

    Article  PubMed  Google Scholar 

  9. Tatasciore A, Zimarino M, Tommasi R, Renda G, Schillaci G, Parati G, De Caterina R (2013) Increased short-term blood pressure variability is associated with early left ventricular systolic dysfunction in newly diagnosed untreated hypertensive patients. J Hypertens 31(8):1653–1661

    Article  CAS  PubMed  Google Scholar 

  10. Tan Z, Meng H, Dong D, Zhao Y, Xu A (2018) Blood pressure variability estimated by ARV is a predictor of poor short-term outcomes in a prospective cohort of minor ischemic stroke. PLoS ONE 13(8):e0202317

    Article  PubMed  PubMed Central  Google Scholar 

  11. Farrag HMA, Amin AS, Abdel-Rheim AR (2019) Relation of short-term blood pressure variability to early renal effects in hypertensive patients with controlled blood pressure. Blood Press Monit 24(5):221–224

    Article  PubMed  Google Scholar 

  12. Jiang D, Kawagoe Y, Asada Y, Kitamura K, Kato J (2020) Augmented blood pressure variability following continuous infusion of noradrenaline in rats. J Hypertens 38(2):314–321

    Article  CAS  PubMed  Google Scholar 

  13. Jiang D, Tokashiki M, Hayashi H, Kawagoe Y, Kuwasako K, Kitamura K, Kato J (2016) Augmented blood pressure variability in hypertension induced by angiotensin II in rats. Am J Hypertens 29(2):163–169

    Article  CAS  PubMed  Google Scholar 

  14. Tohyama T, Hosokawa K, Saku K, Oga Y, Tsutsui H, Sunagawa K (2020) Smart baroreceptor activation therapy strikingly attenuates blood pressure variability in hypertensive rats with impaired baroreceptor. Hypertension 75(3):885–892

    Article  CAS  PubMed  Google Scholar 

  15. Yang ZW, Li DJ, Liu C, Han P, Yang YL, Su DF, Shen FM (2011) Role of vascular KATP channels in blood pressure variability after sinoaortic denervation in rats. Acta Pharmacol Sin 32(2):194–200

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang H, Cheng X, Tian J, Xiao Y, Tian T, Xu F, Hong X, Zhu MX (2020) TRPC channels: structure, function, regulation and recent advances in small molecular probes. Pharmacol Ther 209:107497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Freichel M, Berlin M, Schürger A, Mathar I, Bacmeister L, Medert R, Frede W, Marx A, Segin S, Londoño JEC (2017) Chapter 9, TRP channels in the heart. In: Emir TLR (ed) Neurobiology of TRP Channels, 2nd edn. CRC Press/Taylor & Francis, Boca Raton

    Google Scholar 

  18. Dietrich A, Gudermann T (2014) TRPC6: physiological function and pathophysiological relevance. Handb Exp Pharmacol 222:157–188

    Article  CAS  PubMed  Google Scholar 

  19. Lin BL, Matera D, Doerner JF, Zheng N, Del Camino D, Mishra S, Bian H, Zeveleva S, Zhen X, Blair NT, Chong JA, Hessler DP, Bedja D, Zhu G, Muller GK, Ranek MJ, Pantages L, McFarland M, Netherton MR, Berry A, Wong D, Rast G, Qian HS, Weldon SM, Kuo JJ, Sauer A, Sarko C, Moran MM, Kass DA, Pullen SS (2019) In vivo selective inhibition of TRPC6 by antagonist BI 749327 ameliorates fibrosis and dysfunction in cardiac and renal disease. Proc Natl Acad Sci USA 116(20):10156–10161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liang M, Zhong W, Miao F, Wu H, Liu Y (2018) Effects of losartan on vasomotor function and canonical transient receptor potential channels in the aortas of sinoaortic denervation rats. Clin Exp Hypertens 40(1):39–48

    Article  CAS  PubMed  Google Scholar 

  21. Krieger EM (1964) Neurogenic Hypertension in the Rat. Circ Res 15(6):511–521

    Article  CAS  PubMed  Google Scholar 

  22. Álvarez-Miguel I, Cidad P, Pérez-García MT, López-López JR (2017) Differences in TRPC3 and TRPC6 channels assembly in mesenteric vascular smooth muscle cells in essential hypertension. J Physiol 595(5):1497–1513

    Article  PubMed  Google Scholar 

  23. Doleschal B, Primessnig U, Wölkart G, Wolf S, Schernthaner M, Lichtenegger M, Glasnov TN, Kappe CO, Mayer B, Antoons G, Heinzel F, Poteser M, Groschner K (2015) TRPC3 contributes to regulation of cardiac contractility and arrhythmogenesis by dynamic interaction with NCX1. Cardiovasc Res 106(1):163–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Maier T, Follmann M, Hessler G, Kleemann HW, Hachtel S, Fuchs B, Weissmann N, Linz W, Schmidt T, Löhn M, Schroeter K, Wang L, Rütten H, Strübing C (2015) Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels. Br J Pharmacol 172(14):3650–3660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Radaelli A, Mancia G, De Carlini C, Soriano F, Castiglioni P (2019) patterns of cardiovascular variability after long-term sino-aortic denervation in unanesthetized adult rats. Sci Rep 9(1):1232

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hofmann T, Schaefer M, Schultz G, Gudermann T (2002) Subunit composition of mammalian transient receptor potential channels in living cells. Proc Natl Acad Sci U S A 99(11):7461–7466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Harada M, Luo X, Qi XY, Tadevosyan A, Maguy A, Ordog B, Ledoux J, Kato T, Naud P, Voigt N, Shi Y, Kamiya K, Murohara T, Kodama I, Tardif JC, Schotten U, Van Wagoner DR, Dobrev D, Nattel S (2012) Transient receptor potential canonical-3 channel-dependent fibroblast regulation in atrial fibrillation. Circulation 126(17):2051–2064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang H, Ding J, Fan Q, Liu S (2009) TRPC6 up-regulation in Ang II-induced podocyte apoptosis might result from ERK activation and NF-kappaB Translocation. Exp Biol Med (Maywood) 234(9):1029–1036

    Article  CAS  Google Scholar 

  29. Kai H, Kudo H, Takayama N, Yasuoka S, Aoki Y, Imaizumi T (2014) Molecular mechanism of aggravation of hypertensive organ damages by short-term blood pressure variability. Curr Hypertens Rev 10(3):125–133

    Article  CAS  PubMed  Google Scholar 

  30. dos Santos F, Moraes-Silva IC, Moreira ED, Irigoyen M-C (2018) The role of the baroreflex and parasympathetic nervous system in fructose-induced cardiac and metabolic alterations. Sci Rep 8:10970

    Article  PubMed  PubMed Central  Google Scholar 

  31. Seo K, Rainer PP, Lee DI, Hao S, Bedja D, Birnbaumer L, Cingolani OH, Kass DA (2014) Hyperactive adverse mechanical stress responses in dystrophic heart are coupled to transient receptor potential canonical 6 and blocked by cGMP-protein kinase G modulation. Circ Res 114(5):823–832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wu X, Eder P, Chang B, Molkentin JD (2010) TRPC channels are necessary mediators of pathologic cardiac hypertrophy[J]. Proc Natl Acad Sci U S A 107(15):7000–7005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Piratello AC, Moraes-Silva I, Paulini J, Souza PR, Sirvente PR, Salemi V, Flues K, Moreira ED, Mostarda C, Cunha T, Casarini DE, Irigoyen MC (2010) Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats. Clinics (Sao Paulo) 65(12):1345–1350

    Article  Google Scholar 

  34. Lau O-C, Shen B, Wong C-O, Tjong Y-W, Lo C-Y, Hui-Chuan Wang Yu, Huang W-H, Chen Y-C, Fung M-L, Rudd JA, Yao X (2016) TRPC5 Channels Participate in Pressure-Sensing in Aortic Baroreceptors. Nat Commun 7:11947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Cultivating Fund Project of the First Affiliated Hospital of Chongqing Medical University (PYJJ2018-19). The study was designed by Yu Wang and Shu Qin. The experiments were done by Ling Liu, Yu Wang, Hongmei Tao, and Li Wen. The analysis of the data was done by Ling Liu and Yu Wang. The manuscript was accomplished by Yu Wang and checked by every author. The authors especially thanked Seon Hutson (a doctor from Guyana, an English native speaker) for checking our manuscript.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Yu Wang, Hongmei Tao, Li Wen & Shu Qin

  2. Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Ling Liu

Authors
  1. Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ling Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hongmei Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shu Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shu Qin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Liu, L., Tao, H. et al. TRPC6 participates in the development of blood pressure variability increase in sino-aortic denervated rats. Heart Vessels 35, 1755–1765 (2020). https://doi.org/10.1007/s00380-020-01682-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-020-01682-1

Keywords

Search

Navigation