Evaluation of Serum Urocortin 2 Levels in Patients with Hypertension

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Urocortin 2 (UCN2), is an endogenous stress-related peptide belonging to the corticotropin-releasing factor (CRF) family, has a major role in the pathogenesis of congestive heart failure, ischemic heart disease, and hypertension.


To investigate the role of UCN2 levels in patients with hypertension (HTN).


Serum UCN2 levels measured by ELISA were compared between patients with HTN (n = 86) and nonHTN (n = 53).


Eighty-six patients with HTN [median age 66 (45–76); 38 men] and 53 patients with non-HTN [median age 62 (40–80); 39 men] were included into this study. Serum UCN2 (5.17 ng/ml; IQR, 1.26–11.68 ng/ml vs 0.79 ng/ml; IQR, 0.07–4.10 ng/ml, p < 0.0005) levels were found significantly elevated in patients with HTN compared to nonHTN control group. Concentrations of serum UCN2 were positively correlated with left ventricle mass index to body surface area (LV mass index to BSA, r = 0.20, p = 0.03), LV mass index to height2.7 (r = 0.28, p = 0.002) and body mass index (r = 0.24, p = 0.008). Additionally, logistic regression analysis was performed to UCN2, uric acid, creatinine, glomerular filtration rate, age, body mass index, coronary artery disease and diabetes mellitus which are the potential confounders of hypertension. According to logistic regression analysis serum UCN2 values were found out as an independent predictor of HTN.


UCN2 levels, correlated with LV mass index were increased in HTN patients compared to nonHTN patients. These data provide evidence that there could be a relationship between high concentrations of UCN2 and HTN. UCN2 may appear as a promising choice of HTN treatment in the future.

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  1. 1.

    Hao Z, Huang Y, Cleman J, Jovin IS, Vale WW, Bale TL, et al. Urocortin2 inhibits tumor growth via effects on vascularization and cell proliferation. Proc Natl Acad Sci USA. 2008;105(10):3939–44.

  2. 2.

    Dermitzaki E, Tsatsanis C, Minas V, Chatzaki E, Charalampopoulos I, Venihaki M, et al. Corticotropin-releasing factor (CRF) and the urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type-specific manner. Endocrinology. 2007;148(4):1524–38.

  3. 3.

    Rossant CJ, Pinnock RD, Hughes J, Hall MD, McNulty S. Corticotropin-releasing factor type 1 and type 2alpha receptors regulate phosphorylation of calcium/cyclic adenosine 3′,5′-monophosphate response element-binding protein and activation of p42/p44 mitogen-activated protein kinase. Endocrinology. 1999;140(4):1525–36.

  4. 4.

    Van Kolen K, Dautzenberg FM, Verstraeten K, Royaux I, De Hoogt R, Gutknecht E, et al. Corticotropin releasing factor-induced ERK phosphorylation in AtT20 cells occurs via a cAMP-dependent mechanism requiring EPAC2. Neuropharmacology. 2010;58(1):135–44.

  5. 5.

    Yang LZ, Kockskamper J, Khan S, Suarez J, Walther S, Doleschal B, et al. cAMP- and Ca(2)(+)/calmodulin-dependent protein kinases mediate inotropic, lusitropic and arrhythmogenic effects of urocortin 2 in mouse ventricular myocytes. Br J Pharmacol. 2011;162(2):544–56.

  6. 6.

    Grossini E, Molinari C, Mary DA, Uberti F, Ribichini F, Caimmi PP, et al. Urocortin II induces nitric oxide production through cAMP and Ca2+ related pathways in endothelial cells. Cell Physiol Biochem. 2009;23(1–3):87–96.

  7. 7.

    Ikeda K, Tojo K, Otsubo C, Udagawa T, Hosoya T, Tajima N, et al. Effects of urocortin II on neonatal rat cardiac myocytes and non-myocytes. Peptides. 2005;26(12):2473–81.

  8. 8.

    Grossini E, Molinari C, Mary DA, Marino P, Vacca G. The effect of urocortin II administration on the coronary circulation and cardiac function in the anaesthetized pig is nitric-oxide-dependent. Eur J Pharmacol. 2008;578(2–3):242–8.

  9. 9.

    Dieterle T, Meili-Butz S, Buhler K, Morandi C, John D, Buser PT, et al. Immediate and sustained blood pressure lowering by urocortin 2: a novel approach to antihypertensive therapy? Hypertension. 2009;53(4):739–44.

  10. 10.

    Chen CY, Doong ML, Rivier JE, Tache Y. Intravenous urocortin II decreases blood pressure through CRF(2) receptor in rats. Regul Pept. 2003;113(1–3):125–30.

  11. 11.

    Bale TL, Hoshijima M, Gu Y, Dalton N, Anderson KR, Lee KF, et al. The cardiovascular physiologic actions of urocortin II: acute effects in murine heart failure. Proc Natl Acad Sci USA. 2004;101(10):3697–702.

  12. 12.

    Brar BK, Jonassen AK, Egorina EM, Chen A, Negro A, Perrin MH, et al. Urocortin-II and urocortin-III are cardioprotective against ischemia reperfusion injury: an essential endogenous cardioprotective role for corticotropin releasing factor receptor type 2 in the murine heart. Endocrinology. 2004;145(1):24–35. 21–23).

  13. 13.

    Huang Y, Chan FL, Lau CW, Tsang SY, He GW, Chen ZY, et al. Urocortin-induced endothelium-dependent relaxation of rat coronary artery: role of nitric oxide and K + channels. Br J Pharmacol. 2002;135(6):1467–76.

  14. 14.

    Chen ZW, Huang Y, Yang Q, Li X, Wei W, He GW. Urocortin-induced relaxation in the human internal mammary artery. Cardiovasc Res. 2005;65(4):913–20.

  15. 15.

    Rademaker MT, Cameron VA, Charles CJ, Richards AM. Integrated hemodynamic, hormonal, and renal actions of urocortin 2 in normal and paced sheep: beneficial effects in heart failure. Circulation. 2005;112(23):3624–32.

  16. 16.

    Phrommintikul A, Sivasinprasasn S, Lailerd N, Chattipakorn S, Kuanprasert S, Chattipakorn N. Plasma urocortin in acute myocardial infarction patients. Eur J Clin Invest. 2010;40(10):874–82.

  17. 17.

    Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57(6):450–8.

  18. 18.

    Yang C, Xu Y, Li S. Urocortin: a beneficial or detrimental agent to endothelium? Biochem Biophys Res Commun. 2008;371(3):345–9.

  19. 19.

    Tsuda T, Takefuji M, Wettschureck N, Kotani K, Morimoto R, Okumura T, et al. Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction. J Exp Med. 2017;214(7):1877–88.

  20. 20.

    Liew OW, Yandle TG, Chong JP, Ng YX, Frampton CM, Ng TP, et al. High-sensitivity sandwich ELISA for plasma NT-proUcn2: plasma concentrations and relationship to mortality in heart failure. Clin Chem. 2016;62(6):856–65.

  21. 21.

    Cipriano C, Gosse P, Bemurat L, Mas D, Lemetayer P, N’Tela G, et al. Prognostic value of left ventricular mass and its evolution during treatment in the Bordeaux cohort of hypertensive patients. Am J Hypertens. 2001;14(6 Pt 1):524–9.

  22. 22.

    Rademaker MT, Charles CJ, Nicholls MG, Richards AM. Interactions of enhanced urocortin 2 and mineralocorticoid receptor antagonism in experimental heart failure. Circ Heart Fail. 2013;6(4):825–32.

  23. 23.

    Rademaker MT, Charles CJ, Nicholls G, Richards M. Urocortin 2 sustains haemodynamic and renal function during introduction of beta-blockade in experimental heart failure. J Hypertens. 2011;29(9):1787–95.

  24. 24.

    Rademaker MT, Charles CJ, Nicholls MG, Richards AM. Urocortin 2 combined with angiotensin-converting enzyme inhibition in experimental heart failure. Clin Sci (Lond). 2008;114(10):635–42.

  25. 25.

    Davis ME, Pemberton CJ, Yandle TG, Fisher SF, Lainchbury JG, Frampton CM, et al. Urocortin 2 infusion in healthy humans: hemodynamic, neurohormonal, and renal responses. J Am Coll Cardiol. 2007;49(4):461–71.

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Author information

Concept: GA; supervision: SA; materials: GA; data: GA; analysis: GA; writing: GA; critical revision: SA

Correspondence to Gamze Aslan.

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This study was none funded.

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The authors declare that they have no conflict of interest.

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Aslan, G., Aytekin, S. Evaluation of Serum Urocortin 2 Levels in Patients with Hypertension. High Blood Press Cardiovasc Prev (2020) doi:10.1007/s40292-019-00357-x

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  • Urocortin 2
  • Hypertension
  • Stress