Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension
Dachun Yang, Zhidan Luo, Shuangtao Ma, Wing Tak Wong, Liqun Ma, Jian Zhong, Hongbo He, Zhigang Zhao, Tingbing Cao, Zhencheng Yan, Daoyan Liu, William J Arendshorst, Yu Huang, Martin Tepel, Zhiming Zhu, Dachun Yang, Zhidan Luo, Shuangtao Ma, Wing Tak Wong, Liqun Ma, Jian Zhong, Hongbo He, Zhigang Zhao, Tingbing Cao, Zhencheng Yan, Daoyan Liu, William J Arendshorst, Yu Huang, Martin Tepel, Zhiming Zhu
Abstract
Some plant-based diets lower the cardiometabolic risks and prevalence of hypertension. New evidence implies a role for the transient receptor potential vanilloid 1 (TRPV1) cation channel in the pathogenesis of cardiometabolic diseases. Little is known about impact of chronic TRPV1 activation on the regulation of vascular function and blood pressure. Here we report that chronic TRPV1 activation by dietary capsaicin increases the phosphorylation of protein kinase A (PKA) and eNOS and thus production of nitric oxide (NO) in endothelial cells, which is calcium dependent. TRPV1 activation by capsaicin enhances endothelium-dependent relaxation in wild-type mice, an effect absent in TRPV1-deficient mice. Long-term stimulation of TRPV1 can activate PKA, which contributes to increased eNOS phosphorylation, improves vasorelaxation, and lowers blood pressure in genetically hypertensive rats. We conclude that TRPV1 activation by dietary capsaicin improves endothelial function. TRPV1-mediated increase in NO production may represent a promising target for therapeutic intervention of hypertension.
Copyright 2010 Elsevier Inc. All rights reserved.
Figures
![Figure 1. Location and Functional Characterization of…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3906919/bin/nihms546710f1.jpg)
Figure 2. Activation of TRPV1 Increases Intracellular…
Figure 2. Activation of TRPV1 Increases Intracellular Calcium and Enhances eNOS Activity in the Vasculature
Figure 3. TRPV1-Mediated NO Production Is Associated…
Figure 3. TRPV1-Mediated NO Production Is Associated with Calcium Influx
(A and B) Representative pictures…
Figure 4. Effects of TRPV1 Activation on…
Figure 4. Effects of TRPV1 Activation on PKA Phosphorylation and Activity
(A) The effect of…
Figure 5. Chronic Activation of TRPV1 Enhances…
Figure 5. Chronic Activation of TRPV1 Enhances Endothelium-Dependent Relaxation
(A) Effect of endothelium denudation on…
Figure 6. Role of Perivascular Sensory Nerves…
Figure 6. Role of Perivascular Sensory Nerves in TRPV1-Mediated Relaxation
(A) Representative tracings showing inhibitory…
Figure 7. Effects of TRPV1 Activation on…
Figure 7. Effects of TRPV1 Activation on Blood Pressure and Vascular Relaxation in Spontaneous Hypertensive…
- TRPV1, hypertension, and cardiovascular regulation.Andresen MC, Peters JH. Andresen MC, et al. Cell Metab. 2010 Nov 3;12(5):421; author reply 422. doi: 10.1016/j.cmet.2010.10.004. Cell Metab. 2010. PMID: 21035749 No abstract available.
- TRPV1-mediated UCP2 upregulation ameliorates hyperglycemia-induced endothelial dysfunction.Sun J, Pu Y, Wang P, Chen S, Zhao Y, Liu C, Shang Q, Zhu Z, Liu D. Sun J, et al. Cardiovasc Diabetol. 2013 Apr 22;12:69. doi: 10.1186/1475-2840-12-69. Cardiovasc Diabetol. 2013. PMID: 23607427 Free PMC article.
- Molecular mechanisms of activation of endothelial nitric oxide synthase mediated by transient receptor potential vanilloid type 1.Ching LC, Kou YR, Shyue SK, Su KH, Wei J, Cheng LC, Yu YB, Pan CC, Lee TS. Ching LC, et al. Cardiovasc Res. 2011 Aug 1;91(3):492-501. doi: 10.1093/cvr/cvr104. Epub 2011 Apr 14. Cardiovasc Res. 2011. PMID: 21493704
- TRPV1, hypertension, and cardiovascular regulation.Andresen MC, Peters JH. Andresen MC, et al. Cell Metab. 2010 Nov 3;12(5):421; author reply 422. doi: 10.1016/j.cmet.2010.10.004. Cell Metab. 2010. PMID: 21035749 No abstract available.
- Activation of transient receptor potential vanilloid 1 by dietary capsaicin delays the onset of stroke in stroke-prone spontaneously hypertensive rats.Xu X, Wang P, Zhao Z, Cao T, He H, Luo Z, Zhong J, Gao F, Zhu Z, Li L, Yan Z, Chen J, Ni Y, Liu D, Zhu Z. Xu X, et al. Stroke. 2011 Nov;42(11):3245-51. doi: 10.1161/STROKEAHA.111.618306. Epub 2011 Aug 18. Stroke. 2011. PMID: 21852608
- Structure and function of TRPV1.Tominaga M, Tominaga T. Tominaga M, et al. Pflugers Arch. 2005 Oct;451(1):143-50. doi: 10.1007/s00424-005-1457-8. Epub 2005 Jun 22. Pflugers Arch. 2005. PMID: 15971082 Review.
- Capsaicin: A Potential Treatment to Improve Cerebrovascular Function and Cognition in Obesity and Ageing.Thornton T, Mills D, Bliss E. Thornton T, et al. Nutrients. 2023 Mar 22;15(6):1537. doi: 10.3390/nu15061537. Nutrients. 2023. PMID: 36986266 Free PMC article. Review.
- Expression of cannabinoid (CB1 and CB2) and cannabinoid-related receptors (TRPV1, GPR55, and PPARα) in the synovial membrane of the horse metacarpophalangeal joint.Zamith Cunha R, Zannoni A, Salamanca G, De Silva M, Rinnovati R, Gramenzi A, Forni M, Chiocchetti R. Zamith Cunha R, et al. Front Vet Sci. 2023 Mar 3;10:1045030. doi: 10.3389/fvets.2023.1045030. eCollection 2023. Front Vet Sci. 2023. PMID: 36937015 Free PMC article.
- Research trends in transient receptor potential vanilloid in cardiovascular disease: Bibliometric analysis and visualization.Zhang L, Xu Y, Ma Y, Xie T, Liu C, Liu Q. Zhang L, et al. Front Cardiovasc Med. 2023 Feb 22;10:1071198. doi: 10.3389/fcvm.2023.1071198. eCollection 2023. Front Cardiovasc Med. 2023. PMID: 36910533 Free PMC article.
- Expression of Trpa1 and Trpv1 Genes in the Hypothalamus and Blood Pressure in Normotensive and Hypertensive Rats. Effect of Losartan and Captopril.Kozyreva TV, Voronova IP. Kozyreva TV, et al. Bull Exp Biol Med. 2023 Feb;174(4):426-430. doi: 10.1007/s10517-023-05722-4. Epub 2023 Mar 7. Bull Exp Biol Med. 2023. PMID: 36881283
- Cultured rat aortic vascular smooth muscle cells do not express a functional TRPV1.Blažević T, Ciotu CI, Gold-Binder M, Heiss EH, Fischer MJM, Dirsch VM. Blažević T, et al. PLoS One. 2023 Feb 14;18(2):e0281191. doi: 10.1371/journal.pone.0281191. eCollection 2023. PLoS One. 2023. PMID: 36787302 Free PMC article.
- Research Support, Non-U.S. Gov't
- Animals
- Calcium / metabolism
- Capsaicin / pharmacology*
- Cyclic AMP-Dependent Protein Kinases / metabolism
- Endothelial Cells / enzymology
- Endothelial Cells / metabolism
- Endothelium, Vascular / cytology
- Endothelium, Vascular / physiology*
- Hypertension / prevention & control*
- Mice
- Mice, Inbred C57BL
- Nitric Oxide / metabolism
- Nitric Oxide Synthase Type III / metabolism
- Phosphorylation
- TRPV Cation Channels / deficiency
- TRPV Cation Channels / genetics
- TRPV Cation Channels / metabolism*
- Vasodilation*
- TRPV Cation Channels
- TRPV1 protein, mouse
- Nitric Oxide
- Nitric Oxide Synthase Type III
- Cyclic AMP-Dependent Protein Kinases
- Capsaicin
- Calcium
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
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![Figure 2. Activation of TRPV1 Increases Intracellular…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3906919/bin/nihms546710f2.jpg)
![Figure 3. TRPV1-Mediated NO Production Is Associated…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3906919/bin/nihms546710f3.jpg)
![Figure 4. Effects of TRPV1 Activation on…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3906919/bin/nihms546710f4.jpg)
![Figure 5. Chronic Activation of TRPV1 Enhances…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3906919/bin/nihms546710f5.jpg)
![Figure 6. Role of Perivascular Sensory Nerves…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3906919/bin/nihms546710f6.jpg)
Figure 7. Effects of TRPV1 Activation on…
Figure 7. Effects of TRPV1 Activation on Blood Pressure and Vascular Relaxation in Spontaneous Hypertensive…
- TRPV1, hypertension, and cardiovascular regulation.Andresen MC, Peters JH. Andresen MC, et al. Cell Metab. 2010 Nov 3;12(5):421; author reply 422. doi: 10.1016/j.cmet.2010.10.004. Cell Metab. 2010. PMID: 21035749 No abstract available.
- TRPV1-mediated UCP2 upregulation ameliorates hyperglycemia-induced endothelial dysfunction.Sun J, Pu Y, Wang P, Chen S, Zhao Y, Liu C, Shang Q, Zhu Z, Liu D. Sun J, et al. Cardiovasc Diabetol. 2013 Apr 22;12:69. doi: 10.1186/1475-2840-12-69. Cardiovasc Diabetol. 2013. PMID: 23607427 Free PMC article.
- Molecular mechanisms of activation of endothelial nitric oxide synthase mediated by transient receptor potential vanilloid type 1.Ching LC, Kou YR, Shyue SK, Su KH, Wei J, Cheng LC, Yu YB, Pan CC, Lee TS. Ching LC, et al. Cardiovasc Res. 2011 Aug 1;91(3):492-501. doi: 10.1093/cvr/cvr104. Epub 2011 Apr 14. Cardiovasc Res. 2011. PMID: 21493704
- TRPV1, hypertension, and cardiovascular regulation.Andresen MC, Peters JH. Andresen MC, et al. Cell Metab. 2010 Nov 3;12(5):421; author reply 422. doi: 10.1016/j.cmet.2010.10.004. Cell Metab. 2010. PMID: 21035749 No abstract available.
- Activation of transient receptor potential vanilloid 1 by dietary capsaicin delays the onset of stroke in stroke-prone spontaneously hypertensive rats.Xu X, Wang P, Zhao Z, Cao T, He H, Luo Z, Zhong J, Gao F, Zhu Z, Li L, Yan Z, Chen J, Ni Y, Liu D, Zhu Z. Xu X, et al. Stroke. 2011 Nov;42(11):3245-51. doi: 10.1161/STROKEAHA.111.618306. Epub 2011 Aug 18. Stroke. 2011. PMID: 21852608
- Structure and function of TRPV1.Tominaga M, Tominaga T. Tominaga M, et al. Pflugers Arch. 2005 Oct;451(1):143-50. doi: 10.1007/s00424-005-1457-8. Epub 2005 Jun 22. Pflugers Arch. 2005. PMID: 15971082 Review.
- Capsaicin: A Potential Treatment to Improve Cerebrovascular Function and Cognition in Obesity and Ageing.Thornton T, Mills D, Bliss E. Thornton T, et al. Nutrients. 2023 Mar 22;15(6):1537. doi: 10.3390/nu15061537. Nutrients. 2023. PMID: 36986266 Free PMC article. Review.
- Expression of cannabinoid (CB1 and CB2) and cannabinoid-related receptors (TRPV1, GPR55, and PPARα) in the synovial membrane of the horse metacarpophalangeal joint.Zamith Cunha R, Zannoni A, Salamanca G, De Silva M, Rinnovati R, Gramenzi A, Forni M, Chiocchetti R. Zamith Cunha R, et al. Front Vet Sci. 2023 Mar 3;10:1045030. doi: 10.3389/fvets.2023.1045030. eCollection 2023. Front Vet Sci. 2023. PMID: 36937015 Free PMC article.
- Research trends in transient receptor potential vanilloid in cardiovascular disease: Bibliometric analysis and visualization.Zhang L, Xu Y, Ma Y, Xie T, Liu C, Liu Q. Zhang L, et al. Front Cardiovasc Med. 2023 Feb 22;10:1071198. doi: 10.3389/fcvm.2023.1071198. eCollection 2023. Front Cardiovasc Med. 2023. PMID: 36910533 Free PMC article.
- Expression of Trpa1 and Trpv1 Genes in the Hypothalamus and Blood Pressure in Normotensive and Hypertensive Rats. Effect of Losartan and Captopril.Kozyreva TV, Voronova IP. Kozyreva TV, et al. Bull Exp Biol Med. 2023 Feb;174(4):426-430. doi: 10.1007/s10517-023-05722-4. Epub 2023 Mar 7. Bull Exp Biol Med. 2023. PMID: 36881283
- Cultured rat aortic vascular smooth muscle cells do not express a functional TRPV1.Blažević T, Ciotu CI, Gold-Binder M, Heiss EH, Fischer MJM, Dirsch VM. Blažević T, et al. PLoS One. 2023 Feb 14;18(2):e0281191. doi: 10.1371/journal.pone.0281191. eCollection 2023. PLoS One. 2023. PMID: 36787302 Free PMC article.
- Research Support, Non-U.S. Gov't
- Animals
- Calcium / metabolism
- Capsaicin / pharmacology*
- Cyclic AMP-Dependent Protein Kinases / metabolism
- Endothelial Cells / enzymology
- Endothelial Cells / metabolism
- Endothelium, Vascular / cytology
- Endothelium, Vascular / physiology*
- Hypertension / prevention & control*
- Mice
- Mice, Inbred C57BL
- Nitric Oxide / metabolism
- Nitric Oxide Synthase Type III / metabolism
- Phosphorylation
- TRPV Cation Channels / deficiency
- TRPV Cation Channels / genetics
- TRPV Cation Channels / metabolism*
- Vasodilation*
- TRPV Cation Channels
- TRPV1 protein, mouse
- Nitric Oxide
- Nitric Oxide Synthase Type III
- Cyclic AMP-Dependent Protein Kinases
- Capsaicin
- Calcium
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
![Figure 7. Effects of TRPV1 Activation on…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3906919/bin/nihms546710f7.jpg)
Source: PubMed