Skip to main content

Advertisement

SpringerLink
Log in

Traditional Chinese medicine’s intervention in endothelial nitric oxide synthase activation and nitric oxide synthesis in cardiovascular system

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

Abstract

Cardiovascular disease (CVD) is one of the most dangerous diseases which has become a major cause of human death. Many researches evidenced that nitric oxide (NO)/endothelial nitric oxide synthase (eNOS) system plays a significant role in the occurrence and development of CVD. NO, an important signaling molecule, closely associated with the regulation of vasodilatation, blood rheology, blood clotting and other physiological and pathological processes. The synthesis of NO in the endothelial cells primarily depends on the eNOS activity, thus the exploration of the mechanisms and effects of the eNOS activation on NO production is of great significance. Recently, studies on the effects of traditional Chinese medicine (TCM) and its extracts on eNOS activation and NO synthesis have gradually attracted more and more attentions. In this paper, we reviewed the mechanisms of NO synthesis and eNOS activation in the vascular endothelial cells (VECs) and intervention of TCM, so as to provide reference and train of thought to the intensive study of NO/eNOS system and the research and development of new drug for the treatment of CVD.

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

Similar content being viewed by others

References

  1. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–376.

    Article  CAS  PubMed  Google Scholar 

  2. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327:524–526.

    Article  CAS  PubMed  Google Scholar 

  3. Lamas S, Michel T. Molecular biological features of nitric oxide synthase isoforms. In: Zapol WM, Bloch KD, eds. Nitric oxide and the lung. New York: Marcel Dekker; 1997:59–73.

    Google Scholar 

  4. Förstermann U, Schmidt HH, Pollock JS, Sheng H, Mitchell JA, Warner TD, et al. Isoforms of nitric oxide synthase: characterization and purification from different cell types. Biochem Pharmacol 1991;42:1849–1857.

    Article  PubMed  Google Scholar 

  5. Morris SM, Billiar TR. New insights into the regulation of inducible nitric oxide synthesis. Am J Physiol 1994;266:829–839.

    Google Scholar 

  6. Ricciardolo FL. Multiple roles of nitric oxide in the airways. Thorax 2003;58:175–182.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002–2012.

    Article  CAS  PubMed  Google Scholar 

  8. Balligand JL, Feron O, Dessy C. eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues. Physiol Rev 2009;89:481–534.

    Article  CAS  PubMed  Google Scholar 

  9. Forstermann U, Boissel JP, Kleinert J. Expressional control of the constitutive isoforms of nitric oxide synthase. FASEB J 1998;12:773–790.

    CAS  PubMed  Google Scholar 

  10. Feron O, Balligand JL. Caveolins and the regulation of endothelial nitric oxide synthase in the heart. Cardiovasc Res 2006;69:788–797.

    Article  CAS  PubMed  Google Scholar 

  11. Feron O, Belhassen L, Kobzik L, Smith TW, Kelly RA, Michel T. Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem 1996;271:22810–22814.

    Article  CAS  PubMed  Google Scholar 

  12. Li S, Couet J, Lisanti MP. Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. J Biol Chem 1996;271:29182–29190.

    Article  CAS  PubMed  Google Scholar 

  13. García-Cardena G, Martasek P, Masters BS, Skidd PM, Couet J, Li S, et al. Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the NOS caveolin binding domain in vivo. J Biol Chem 1997;272:25437–25440.

    Article  PubMed  Google Scholar 

  14. Bucci M, Gratton JP, Rudic RD, Acevedo L, Roviezzo F, Cirino G, et al. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat Med 2000;6:1362–1367.

    Article  CAS  PubMed  Google Scholar 

  15. Ghosh S, Gachhui R, Crooks C, Wu CQ, Lisanti MP, Stuehr DJ. Interaction between caveolin-1 and the reductase domain of endothelial nitric-oxide synthase-consequences for catalysis. J Biol Chem 1998;273:22267–22271.

    Article  CAS  PubMed  Google Scholar 

  16. Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, et al. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 2001;293:2449–2452.

    Article  CAS  PubMed  Google Scholar 

  17. Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, et al. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 2001;276:38121–38138.

    Article  CAS  PubMed  Google Scholar 

  18. Dedio J, Konig P, Wohlfart P, Schroeder C, Kummer W, Muller-Esterl W. NOSIP, a novel modulator of endothelial nitric oxide synthase activity. FASEB J 2001;15:79–89.

    Article  CAS  PubMed  Google Scholar 

  19. Zimmermann K, Opitz N, Dedio J, Renne C, Muller-Esterl W, Oess S. NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 2002;99:17167–17172.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Schilling K, Opitz N, Wiesenthal A, Oess S, Tikkanen R, Müller-Esterl W, et al. Translocation of endothelial nitricoxide synthase involves a ternary complex with Caveolin-1 and NOSTRIN. Mol Cell Biol 2006;17:3870–3880.

    Article  CAS  Google Scholar 

  21. Hong Wang, Aileen X. Wang, Zhenqi Liu, Weidong Chai, Eugene J. Barrett. The trafficking/interaction of eNOS and Caveolin-1 induced by insulin modulates endothelial nitri oxide production. Mol Endocrinol 2009;23:1613–1623.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Chen DB, Jia S, King AG, Barker A, Li SM, Mata-Greenwood E, et al. Globalprotein expression profiling underlines reciprocal regulation of caveolin-1 and endothelial nitric oxide synthase expression in ovariectomized sheep uterine artery by estrogen/progesterone replacement therapy. Biol Reprod 2006;74:832–838.

    Article  CAS  PubMed  Google Scholar 

  23. Sud N, Wiseman DA, Black SM. Caveolin 1 is required for the activation of endothelial nitric oxide synthase in response to 17β-estradiol. Mol Endocrinol 2010;24:1637–1649.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Zhou XP, He PN. Endothelial [Ca2+]i and caveolin-1 antagonistically regulate eNOS activity and microvessel permeability in rat venules. Cardiovasc Res 2010;87:340–347.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Maniatis NA, Brovkovych V, Allen SE, John TA, Shajahan AN, Tiruppathi C, et al. Novel mechanism of endothelial nitric oxide synthase activation mediated by caveolae internalization in endothelial cells. Circ Res 2006;99:870–877.

    Article  CAS  PubMed  Google Scholar 

  26. Chen Z, Bakhshi FR, Shajahan AN, Sharma T, Mao M, Trane A, et al. Nitric oxide-dependent Src activation and resultant caveolin-1 phosphorylation promote eNOS/caveolin-1 binding and eNOS inhibition. Mol Biol Cell 2012;23:1388–1398.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Gratton JP, Fontana J, O’Connor DS, Garcia-Cardena G, McCabe TJ, Sessa WC. Reconstitution of an endothelial nitric-oxide synthase (eNOS), Hsp90, and Caveolin-1 complex in vitro. J Biol Chem 2000;275:22268–22272.

    Article  CAS  PubMed  Google Scholar 

  28. García-Cardeña G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A, et al. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 1998;392:821–824.

    Article  PubMed  Google Scholar 

  29. Averna M, Stifanese R, De Tullio R, Salamino F, Pontremoli S, Melloni E. In vivo degradation of nitric oxide synthase (NOS) and heat shock protein 90 (HSP90) by calpain is modulated by the formation of a NOS-HSP90 heterocomplex. FEBS J 2008;275:2501–2511.

    Article  CAS  PubMed  Google Scholar 

  30. Averna M, Stifanese R, De Tullio R, Salamino F, Bertuccio M, Pontremoli S, et al. Proteolytic degradation of nitric oxide synthase isoforms by calpain is modulated by the expression levels of HSP90. FEBS J 2007;274:6116–6127.

    Article  CAS  PubMed  Google Scholar 

  31. Aschner JL, Foster SL, Kaplowitz M, Zhang Y, Zeng H, Fike CD. Heat shock protein 90 modulates endothelial nitric oxide synthase activity and vascular reactivity in the newborn piglet pulmonary circulation. Am J Physiol Lung Cell Mol Physiol 2007;292:L1515–L1525.

    Article  CAS  PubMed  Google Scholar 

  32. Segnitz B, Gehring U. The function of steroid hormone receptors is inhibited by the hsp90-specific compound geldanamycin. J Biol Chem 1997;272:18694–18701.

    Article  CAS  PubMed  Google Scholar 

  33. Fontana J, Fulton D, Chen Y, Fairchild TA, McCabe TJ, Fujita N, et al. Domain mapping studies reveal that the M domain of hsp90 serves as a molecular scaffold to regulate Akt-dependent phosphorylation of endothelial nitric oxide synthase and NO release. Circ Res 2002;90:866–873.

    Article  CAS  PubMed  Google Scholar 

  34. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999;399:601–605.

    Article  CAS  PubMed  Google Scholar 

  35. Fulton D, Gratton JP, Mccabe TJ, Fontana J, Fujio Y, Walsh K, et al. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 1999;399:597–601.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Fleming I, Fisslthaler B, Dimmeler S, Kemp BE, Busse R. Phosphorylation of Thr(495) regulates Ca(2+)/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res 2001;88:E68–75.

    Article  CAS  PubMed  Google Scholar 

  37. Michell BJ, Chen Zp, Tiganis T, Stapleton D, Katsis F, Power DA, et al. Coordinated control of endothelial nitricoxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 2001;276:17625–17628.

    Article  CAS  PubMed  Google Scholar 

  38. Butt E, Bernhardt M, Smolenski A, Kotsonis P, Fröhlich LG, Sickmann A, et al. Endothelial nitric-oxide synthase (type III) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases. J Biol Chem 2000;275:5179–5187.

    Article  CAS  PubMed  Google Scholar 

  39. Davda RK, Chandler LJ, Guzman NJ. Protein kinase C modulates receptor-independent activation of endothelial nitric oxide synthase. Eur J Pharmacol 1994;266:237–244.

    Article  CAS  PubMed  Google Scholar 

  40. Lin MI, Fulton D, Babbitt R, Fleming I, Busse R, Pritchard KA Jr, et al. Phosphorylation of threonine 497 in endothelial nitric-oxide synthase coordinates the coupling of L-arginine metabolism to efficient nitric oxide production. J Biol Chem 2003;278:44719–44726.

    Article  CAS  PubMed  Google Scholar 

  41. Fisslthaler B, Fleming I. Activation and signaling by the AMP-activated protein kinase in endothelial cells. Circ Res 2009;105:114–127.

    Article  CAS  PubMed  Google Scholar 

  42. Chen Z, Peng IC, Sun W, Su MI, Hsu PH, Fu Y, et al. AMP-activated protein kinase functionally phosphorylates endothelial nitric oxide synthase Ser633. Circ Res 2009;104:496–505.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Aoyagi M, Arvai AS, Tainer JA, Getzoff ED. Structural basis for endothelial nitric oxide synthase binding to calmodulin. EMBO J 2003;22:766–775.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Corson MA, James NL, Latta SE, Nerem RM, Berk BC, Harrison DG. Phosphorylation of endothelial nitric oxide synthase in response to fluid shear stress. Circ Res 1996;79:984–991.

    Article  CAS  PubMed  Google Scholar 

  45. Fleming I, Bauersachs J, Fisslthaler B, Busse R. Ca2+-independent activation of the endothelial nitric oxide synthase inresponse to tyrosine phosphatase inhibitors and fluid shear stress. Circ Res 1998;82:686–695.

    Article  CAS  PubMed  Google Scholar 

  46. Busse R, Mülsch A. Calcium-dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin. FEBS Lett 1990;265:133–136.

    Article  CAS  PubMed  Google Scholar 

  47. Gratton JP, Fontana J, O’Connor DS, García-Cardena G, Mccabe TJ, Sessa WC. Reconstitution of an endothelial nitric oxide synthase, hsp90 and caveolin-1 complex in vitro: evidence that hsp90 facilitates calmodulin stimulated displace-ment of eNOS from caveolin-1. J Biol Chem 2000;275:22268–22272.

    Article  CAS  PubMed  Google Scholar 

  48. Channon K. Tetrahydrobiopterin: regulator of endothelial nitric oxide synthase in vascular disease. Trends Cardiovasc Med 2004;14:323–327.

    Article  CAS  PubMed  Google Scholar 

  49. Widder JD, Chen W, Li L, Dikalov S, Thöny B, Hatakeyama K, et al. Regulation of tetrahydrobiopterin biosynthesis by shear stress. Circ Res 2007;101:830–838.

    Article  CAS  PubMed  Google Scholar 

  50. Newman PJ. Switched at birth: a new family for PECAM-1. J Clin Invest 1999;103:5–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Chiu YJ, Kusano K, Thomas TN, Fujiwara K. Endothelial cell-cell adhesion and mechano-signal transduction. Endothelium 2004;11:59–73.

    Article  CAS  PubMed  Google Scholar 

  52. Fleming I, Fisslthaler B, Dixit M, Busse R. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells. J Cell Sci 2005;118:4103–4111.

    Article  CAS  PubMed  Google Scholar 

  53. Fleming I. Molecular mechanisms underlying the activation of eNOS. Pflugers Arch 2010;459:793–806.

    Article  CAS  PubMed  Google Scholar 

  54. Chalupsky K, Cai H. Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 2005;102:9056–9061.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Leung KW, Cheng YK, Mak NK, Chan KK, Fan TP, Wong RN. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Lett 2006;580:3211–3216.

    Article  CAS  PubMed  Google Scholar 

  56. Yu J, Eto M, Akishita M, Kaneko A, Ouchi Y, Okabe T. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor. Biochem Biophys Res Commun 2007;353:764–769.

    Article  CAS  PubMed  Google Scholar 

  57. Leung KW, Leung FP, Mak NK, Tombran-Tink J, Huang Y, Wong RN. Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells. Br J Pharmacol 2009;156:626–637.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Ahn HY, Hong SY, Kim JY, Kwon O. Panax ginseng extract rich in ginsenoside protopanaxatriol offers combinatorial effects in nitric oxide production via multiple signaling pathways. Springerplus 2013;2:96.

    Article  PubMed Central  PubMed  Google Scholar 

  59. Hien TT, Kim ND, Pokharel YR, Oh SJ, Lee MY, Kang KW. Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: Essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase. Toxicol Appl Pharmacol 2010;246:171–183.

    Article  CAS  PubMed  Google Scholar 

  60. Hwang YP, Kim HG, Hien TT, Jeong MH, Jeong TC, Jeong HG. Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase. Toxicol Appl Pharmacol 2011;257:48–58.

    Article  CAS  PubMed  Google Scholar 

  61. Kim HG, Hien TT, Han EH, Chung YC, Jeong HG. Molecular mechanism of endothelial nitric-oxide synthase activation by Platycodon grandiflorum root-derived saponins. Toxicol Lett 2010;195:106–113.

    Article  CAS  PubMed  Google Scholar 

  62. Chung BH, Kim S, Kim JD, Lee JJ, Baek YY, Jeoung D, et al. Syringaresinol causes vasorelaxation by elevating nitric oxide production through the phosphorylation and dimerization of endothelial nitric oxide synthase. Exp Mol Med 2012;44:191–201.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Koltermann A, Hartkorn A, Koch E, Fürst R, Vollmar AM, Zahler S. Ginkgo biloba extract EGb761 increases endothelial nitric oxide production in vitro and in vivo. Cell Mol Life Sci 2007;64:1715–1722.

    Article  CAS  PubMed  Google Scholar 

  64. Kang Y, Hu M, Zhu Y, Gao X, Wang MW. Antioxidative effect of the herbal remedy Qin Huo Yi Hao and its active component tetramethylpyrazine on high glucose-treated endothelial cells. Life Sci 2009;84:428–436.

    Article  CAS  PubMed  Google Scholar 

  65. Wang Y, Huang Y, Lam KS, Li Y, Wong WT, Ye H, et al. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res 2009;82:484–492.

    Article  CAS  PubMed  Google Scholar 

  66. Xu Q, Hao X, Yang Q, Si L. Resveratrol prevents hyperglycemia-induced endothelial dysfunction via activation of adenosine monophosphate-activated protein kinase. Biochem Biophys Res Commun 2009;388:389–394.

    Article  CAS  PubMed  Google Scholar 

  67. Hien TT, Oh WK, Quyen BT, Dao TT, Yoon JH, Yun SY, et al. Potent vasodilation effect of amurensin G is mediated through the phosphorylation of endothelial nitric oxide synthase. Biochem Pharmacol 2012;84:1437–50.

    Article  CAS  PubMed  Google Scholar 

  68. Hien TT, Oh WK, Nguyen PH, Oh SJ, Lee MY, Kang KW. Nectandrin B activates endothelial nitric-oxide synthase phosphorylation in endothelial cells: Role of the AMP-activated protein kinase/estrogen receptor α/phosphatidylinositol 3-kinase/Akt pathway. Mol Pharmacol 2011;80:1166–1178.

    Article  CAS  PubMed  Google Scholar 

  69. Guo Y, Zhu B Y, Yan FX, Liao DF. Protective action and of onychin against growth inhibition of endothelial cell injured by oxidation and its mechanism. Chin Pharmacol Bull (Chin) 2003;19:401–403.

    CAS  Google Scholar 

  70. Wang W, Xu B. Effects of depside salt from Salvia Miltiorrhiza on latelet endothelial nitric oxide synthase activity. Chin J Hypertension (Chin) 2007;15:554–556.

    CAS  Google Scholar 

  71. Fu JJ, Wang XL, Lv H, Liu R, Yin XY, Zheng YB, et al. Antihypertensive effects of extracts from leaves of Apocynum venetum through activating PI3K /Akt pathway on human endothelial cells. Chin J Exp Tradit Med Formulae (Chin) 2013;19:159–164.

    Google Scholar 

  72. Yao L, Lu P, Li Y, Yang L, Feng H, Huang Y, et al. Osthole relaxes pulmonary arteries through endothelial phosphatidylinositol 3-kinase/Akt-eNOS-NO signaling pathway in rats. Eur J Pharmacol 2013;699:23–32.

    Article  CAS  PubMed  Google Scholar 

  73. Boo YC, Sorescu GP, Bauer PM, Fulton D, Kemp BE, Harrison DG, et al. Endothelial NO synthase phosphorylated at SER635 produees NO without requiring intracellular calcium increase. Free Radic Biol Med 2003;35:729–741.

    Article  CAS  PubMed  Google Scholar 

  74. McCabe TJ, Fulton D, Roman LJ, Sessa WC. Enhanced electron flux and reduced calmodulin dissociation may explain “calcium-independent” eNOS activation by phosphorylation. J Biol Chem 2000;275:6123–6128.

    Article  CAS  PubMed  Google Scholar 

  75. Du GH, Wang YH, Zhang R, Tan CB, He XL, Hu JJ, et al. Multi-component and multi-target is a surface understanding of the mechanism of traditional Chinese medicine. World Sci Technol (Chin) 2009;11:480–484.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Traditional Chinese Medicine, Tianjin Key Laboratory of Chinese Medical Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Jin-qiang Zhu  (朱金墙), Zhen Hu  (胡 珍), Qiao-feng Ye  (叶乔峰), Yu-bin Liang  (梁钰彬) & Li-yuan Kang  (康立源)

  2. Encephalopathy Department, the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300150, China

    Wan-shan Song  (宋宛珊)

Authors
  1. Jin-qiang Zhu  (朱金墙)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wan-shan Song  (宋宛珊)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhen Hu  (胡 珍)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qiao-feng Ye  (叶乔峰)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yu-bin Liang  (梁钰彬)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Li-yuan Kang  (康立源)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Li-yuan Kang  (康立源).

Additional information

Supported by the National Key Basic Research and Development Program of China (No. 2012CB518404)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhu, Jq., Song, Ws., Hu, Z. et al. Traditional Chinese medicine’s intervention in endothelial nitric oxide synthase activation and nitric oxide synthesis in cardiovascular system. Chin. J. Integr. Med. (2015). https://doi.org/10.1007/s11655-015-1964-1

Download citation

  • Received:

  • Published:

  • DOI: https://doi.org/10.1007/s11655-015-1964-1

Keywords

Search

Navigation