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Published in: Heart and Vessels 12/2020

01-12-2020 | Neurotomy | Original Article

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

Authors: Yu Wang, Ling Liu, Hongmei Tao, Li Wen, Shu Qin

Published in: Heart and Vessels | Issue 12/2020

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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.
Literature
1.
go back to reference 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):e034355CrossRefPubMedPubMedCentral 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):e034355CrossRefPubMedPubMedCentral
2.
go back to reference 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:i4098CrossRefPubMedPubMedCentral 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:i4098CrossRefPubMedPubMedCentral
3.
go back to reference 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):163CrossRef 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):163CrossRef
4.
go back to reference 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):1125–1135CrossRefPubMed 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):1125–1135CrossRefPubMed
5.
go back to reference Parati G, Ochoa JE, Lombardi C, Bilo G (2013) Assessment and management of blood-pressure variability. Nat Rev Cardiol 10(3):143–155CrossRefPubMed Parati G, Ochoa JE, Lombardi C, Bilo G (2013) Assessment and management of blood-pressure variability. Nat Rev Cardiol 10(3):143–155CrossRefPubMed
6.
go back to reference 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):382–389CrossRefPubMedPubMedCentral 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):382–389CrossRefPubMedPubMedCentral
7.
go back to reference 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):895–905CrossRef 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):895–905CrossRef
8.
go back to reference 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):489–497CrossRefPubMed 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):489–497CrossRefPubMed
9.
go back to reference 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):1653–1661CrossRefPubMed 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):1653–1661CrossRefPubMed
10.
go back to reference 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):e0202317CrossRefPubMedPubMedCentral 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):e0202317CrossRefPubMedPubMedCentral
11.
go back to reference 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):221–224CrossRefPubMed 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):221–224CrossRefPubMed
12.
go back to reference 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):314–321CrossRefPubMed 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):314–321CrossRefPubMed
13.
go back to reference 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):163–169CrossRefPubMed 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):163–169CrossRefPubMed
14.
go back to reference 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):885–892CrossRefPubMed 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):885–892CrossRefPubMed
15.
go back to reference 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):194–200CrossRefPubMedPubMedCentral 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):194–200CrossRefPubMedPubMedCentral
16.
go back to reference 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 209:107497CrossRefPubMedPubMedCentral 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 209:107497CrossRefPubMedPubMedCentral
17.
go back to reference 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 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
18.
go back to reference Dietrich A, Gudermann T (2014) TRPC6: physiological function and pathophysiological relevance. Handb Exp Pharmacol 222:157–188CrossRefPubMed Dietrich A, Gudermann T (2014) TRPC6: physiological function and pathophysiological relevance. Handb Exp Pharmacol 222:157–188CrossRefPubMed
19.
go back to reference 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):10156–10161CrossRefPubMedPubMedCentral 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):10156–10161CrossRefPubMedPubMedCentral
20.
go back to reference 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):39–48CrossRefPubMed 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):39–48CrossRefPubMed
22.
go back to reference 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):1497–1513CrossRefPubMed 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):1497–1513CrossRefPubMed
23.
go back to reference 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):163–173CrossRefPubMedPubMedCentral 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):163–173CrossRefPubMedPubMedCentral
24.
go back to reference 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):3650–3660CrossRefPubMedPubMedCentral 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):3650–3660CrossRefPubMedPubMedCentral
25.
go back to reference 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):1232CrossRefPubMedPubMedCentral 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):1232CrossRefPubMedPubMedCentral
26.
go back to reference 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):7461–7466CrossRefPubMedPubMedCentral 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):7461–7466CrossRefPubMedPubMedCentral
27.
go back to reference 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):2051–2064CrossRefPubMedPubMedCentral 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):2051–2064CrossRefPubMedPubMedCentral
28.
go back to reference 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):1029–1036CrossRef 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):1029–1036CrossRef
29.
go back to reference 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):125–133CrossRefPubMed 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):125–133CrossRefPubMed
30.
go back to reference 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 8:10970CrossRefPubMedPubMedCentral 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 8:10970CrossRefPubMedPubMedCentral
31.
go back to reference 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):823–832CrossRefPubMedPubMedCentral 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):823–832CrossRefPubMedPubMedCentral
32.
go back to reference 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):7000–7005CrossRefPubMedPubMedCentral 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):7000–7005CrossRefPubMedPubMedCentral
33.
go back to reference 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):1345–1350CrossRef 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):1345–1350CrossRef
34.
go back to reference 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 7:11947CrossRefPubMedPubMedCentral 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 7:11947CrossRefPubMedPubMedCentral
Metadata
Title
TRPC6 participates in the development of blood pressure variability increase in sino-aortic denervated rats
Authors
Yu Wang
Ling Liu
Hongmei Tao
Li Wen
Shu Qin
Publication date
01-12-2020
Publisher
Springer Japan
Keyword
Neurotomy
Published in
Heart and Vessels / Issue 12/2020
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-020-01682-1

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