Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Central systolic blood pressure relates inversely to nitric oxide synthesis in young black adults: the African-PREDICT study



Lower nitric oxide (NO) bioavailabilty associates with hypertension in patients and elderly populations. With hypertension known to develop earlier in black populations, we compared both plasma and urinary NO-related markers and their associations with central systolic blood pressure (cSBP) and arterial stiffness in healthy young black and white adults. We included healthy black and white men and women (n = 1110; 20–30 years) and measured cSBP and pulse wave velocity (PWV), along with both plasma and urinary arginine, homoarginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), as well as urinary ornithine/citrulline, nitrite and nitrate. In addition, the urinary nitrate-to-nitrite ratio (UNOxR) was calculated. The black men and women had higher cSBP and higher plasma arginine and ADMA, but lower urinary nitrate and UNOxR (all p ≤ 0.003) than their white counterparts. In single and forward stepwise multiple regression analyses, we found an inverse association of cSBP (adj. R2 = 0.124; β = –0.134; p = 0.006) and plasma homoarginine in black men. Central SBP associated inversely with UNOxR in black women only (adj. R2 = 0.171; β = –0.130; p = 0.029). In the white women, cSBP associated positively with urinary ADMA (adj. R2 = 0.372; β = 0.162; p = 0.015). PWV associated inversely with plasma ADMA (adj. R2 = 0.253; β = –0.163; p = 0.024) in the white women only. The lower NO synthesis and the higher cSBP in our black cohort support the notion of a potential increased risk for future large artery stiffness and hypertension development in later life.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Fig. 1: A comparison of NO related biomarkes stratefied by sex and ethnicity.


  1. Opie LH. Heart disease in Africa. Lancet. 2006;368:449–50.

    Article  Google Scholar 

  2. Zhou D, Xi B, Zhao M, Wang L, Veeranki SP. Uncontrolled hypertension increases risk of all-cause and cardiovascular disease mortality in US adults: the NHANES III Linked Mortality Study. Sci Rep. 2018;8:9418.

    Article  Google Scholar 

  3. Li Q, Yon JY, Cai H. Mechanisms and Consequences of eNOS Dysfunction in Hypertension. J Hypertension. 2016;33:1128–36.

    Article  Google Scholar 

  4. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharm Rev. 1991;43:109–42.

    CAS  PubMed  Google Scholar 

  5. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7:156–67.

    Article  CAS  Google Scholar 

  6. Naseem KM. The role of nitric oxide in cardiovascular diseases. Mol Asp Med. 2005;26:33–65.

    Article  CAS  Google Scholar 

  7. Reckelhoff JF, Kellum JA, Blanchard EJ, Bacon EE, Wesley AJ, Kruckeberg WC. Changes in nitric oxide precursor, L-arginine, and metabolites, nitrate and nitrite, with aging. Life Sci. 1994;55:1895–902.

    Article  CAS  Google Scholar 

  8. Takase H, Sugiyama M, Nakazawa A, Sato K, Ueda R, Dohi Y. Long-term effect of antihypertensive therapy with calcium antagonist or angiotensin converting enzyme inhibitor on serum nitrite/nitrate levels in human essential hypertension. Arzneimittelforschung. 2000;50:530–4.

    CAS  PubMed  Google Scholar 

  9. Wang H, Liu J. Plasma asymmetric dimethylarginine and L-arginine levels in Chinese patients with essential hypertension without coronary artery disease. J Cardiovasc Dis Res. 2011;2:177–80.

    Article  CAS  Google Scholar 

  10. Glyn MC, Anderssohn M, Lüneberg N, Van Rooyen JM, Schutte R, Huisman HW, et al. Ethnic-specific differences in L-arginine status in South African men. J Hum Hypertens. 2012;26:737–43.

    Article  CAS  Google Scholar 

  11. Mels CM, Huisman HW, Smith W, Schutte R, Schwedhelm E, Atzler D, et al. The relationship of nitric oxide synthesis capacity, oxidative stress, and albumin-to-creatinine ratio in black and white men: the SABPA study. Age. 2016;38:9.

    Article  Google Scholar 

  12. Schutte AE, Schutte R, Huisman HW, Van Rooyen JM, Fourie CM, Malan L, et al. Dimethylarginines: their vascular and metabolic roles in African and Caucasians. Eur J Endocrinol. 2010;162:525–33.

    Article  CAS  Google Scholar 

  13. Schutte AE, Gona PN, Delles C, Uys AS, Burger A, Mels CMC, et al. The African Prospective study on the early detection and identification of cardiovascular disease and hypertension (African-PREDICT): design, recruitment and initial examination. Eur. J Prev Cardiol. 2019;26:458–70.

    Article  Google Scholar 

  14. Carlson RV, Boyd KM, Webb DJ. The revision of the Declaration of Helsinki: past, present and future. Br J Clin Pharm. 2004;57:659–713.

    Article  Google Scholar 

  15. Kiers HD, Hofstra JM, Wetzels JFM. Oscillometric blood pressure measurements: differences between measured and calculated mean arterial pressure. J Med. 2008;66:474–9.

    CAS  Google Scholar 

  16. Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, et al. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012;30:445–8.

    Article  Google Scholar 

  17. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Eng J Med. 2012;367:20–29.

    Article  CAS  Google Scholar 

  18. Schwedhelm E, Tan-Andresen J, Maas R, Riederer U, Schulze F, Böger RH. Liquid chromatography-tandem mass spectrometry method for the analysis of asymmetric dimethylarginine in human plasma. Clin Chem. 2005;51:1268–71.

    Article  CAS  Google Scholar 

  19. Atzler D, Mieth M, Maas R, Böger RH, Schwedhelm E. Stable isotope dilution assay for liquid chromatography-tandem mass spectrometric determination of L-homoarginine in human plasma. J Chromatogr B Anal Technnol Biomed Life Sci. 2011;879:2294–8.

    Article  CAS  Google Scholar 

  20. Hanff E, Lützow M, Kayacelebi AA, Finkel A, Maassen M, Yanchev GR, et al. Simultaneous GC-ECNICI-MS measurement of nitrite, nitrate and creatinine in human urine and plasma in clinical settings. J Chromatogr B Anal Technol Biomed Life Sci. 2017a;2017:207–14.

    Article  Google Scholar 

  21. Tsikas D, Hanff E, Bollenbach A, Kruger R, Pham VV, Chobanyan-Jürgens K, et al. Results, meta-analysis and a first evaluation of UNOxR, the urinary nitrate-to-nitrite molar ratio, as a measure of nitrite reabsorption in experimental and clinical settings. Amino Acids. 2018;50:799–821.

    Article  CAS  Google Scholar 

  22. Melikian N, Wheatcroft SB, Ogah OS, Murphy C, Chowienczyk PJ, Wierzbicki AS, et al. Asymmetric dimethylarginine and reduced nitric oxide bioavailability in young Black African men. Hypertension. 2007;49:873–7.

    Article  CAS  Google Scholar 

  23. Moss MB, Brunini TM, Soares De Moura R, Novaes Malagris LE, Roberts NB, Ellory JC, et al. Diminished L-arginine bioavailability in hypertension. Clin Sci. 2004;107:391–7.

    Article  CAS  Google Scholar 

  24. Perticone F, Sciacqua A, Maio R, Perticone M, Maas R, Böger RH, et al. Asymmetric dimethylarginine, L-arginine and endothelial dysfunction in essential hypertension. J Am Coll Cardiol. 2005;46:518–23.

    Article  CAS  Google Scholar 

  25. Van der Zwan LP, Davids M, Scheffer PG, Dekker JM, Stehouwer CD. Teerlink T. L-Homoarginine and L-arginine are antagonistically related to blood pressure in elderly population: the Hoorn Study. J Hypertens. 2013;31:1114–23.

    Article  Google Scholar 

  26. Litwin M, Obrycki L, Niemirska A, Sarnecki J, Kulaga Z. Central systolic blood pressure and central pulse pressure predict left ventricular hypertrophy in hypertensive children. Pediatr Nephrol. 2019;34:703–12.

    Article  Google Scholar 

  27. Schneider JY, Rothmann S, Schröder F, Langen J, Lücke T, Mariotti F, et al. Effects of chronic oral L-arginine administration on the L-arginine/NO pathway in patients with peripheral arterial occlusive disease or coronary artery disease: L-Arginine prevents renal loss of nitrite, the major NO reservoir. Amino Acids. 2005;47:1961–74.

    Article  Google Scholar 

  28. Said MY, Bollenbach A, Minović I, Van Londen M, Frenay AR, de Borst MH, et al. Plasma ADMA, Urinary ADMA excretion, and late mortality in renal transplant recipients. Amino Acids. 2019;51:913–27.

    Article  CAS  Google Scholar 

  29. Bode-Böger SM, Scalera F, Kielstein JT, Martens-Lobenhoffer J, Breithardt G, Fobker M, et al. Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease. J Am Soc Nephrol. 2006;17:1128–34.

    Article  Google Scholar 

  30. Matsuoka H, Itoh S, Kimoto M, Kohno K, Tamai O, Wada Y, et al. Asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental. Hypertension Hypertension. 1997;29:242–7.

    Article  CAS  Google Scholar 

  31. Wolf C, Lorenzen JM, Stein S, Tsikas D, Störk S, Weidemann F, et al. Urinary asymmetric dimethylarginine (ADMA) is a predictor of mortality risk in patients with coronary artery disease. Int J Cardiol. 2012;156:289–94.

    Article  Google Scholar 

  32. Gkaliagkousi E, Gavriilaki E, Triantafyllou A, Nikolaidou B, Anyfanti P, Koletsos N, et al. Asymmetric dimethylarginine levels associated with augmentation index across naïve untreated patients with different hypertension phenotypes. J Clin Hypertens. 2018;20:680–5.

    Article  CAS  Google Scholar 

  33. Serg M, Kampus P, Kals J, Zagura M, Muda P, Tuomainen TP, et al. Association between asymmetric dimethylarginine and indices of vascular function in patients with essential hypertension. Blood Press. 2011;20:111–6.

    Article  CAS  Google Scholar 

  34. Päivä H, Kähönen M, Lehtimäki T, Raitakari OT, Jula A, Viikari J, et al. Asymmetric Dimethylarginine (ADMA) has a role in regulating systemic vascular tone in young healthy subjects: the cardiovascular risk in Young Finn Study. Am J Hypertens. 2008;21:873–8.

    Article  Google Scholar 

  35. Kielstein JT, Impraim B, Simmel S, Bode-Böger SM, Tsikas D, Frölich JC, et al. Cardiovascular effects of systemic nitric oxide synthase inhibition with asymmetric dimethylarginine in humans. Circulation. 2004;109:172–7.

    Article  CAS  Google Scholar 

Download references


The authors are grateful towards all individuals participating voluntarily in the African-PREDICT study. The dedication of the support and research staff as well as students at the Hypertension Research and Training Clinic at the North-West University (Potchefstroom campus) are also duly acknowledged.


Funding The African-PREDICT study: The research funded in this manuscript is part of an ongoing research project financially supported by the South African Medical Research Council (SAMRC) with funds from National Treasury under its Economic Competitiveness and Support Package; the South African Research Chairs Initiative (SARChI) of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (GUN 86895); SAMRC with funds received from the South African National Department of Health, GlaxoSmithKline R&D (Africa Non-Communicable Disease Open Lab grant), the UK Medical Research Council and with funds from the UK Government’s Newton Fund; as well as corporate social investment grants from Pfizer (South Africa), Boehringer-Ingelheim (South Africa), Novartis (South Africa), the Medi Clinic Hospital Group (South Africa) and in kind contributions of Roche Diagnostics (South Africa). Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors, and therefore, the NRF does not accept any liability in this regard.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Ruan Kruger.

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.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Craig, A., M. C. Mels, C., Tsikas, D. et al. Central systolic blood pressure relates inversely to nitric oxide synthesis in young black adults: the African-PREDICT study. J Hum Hypertens 35, 985–993 (2021).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links