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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1776.)
© 2007 American Heart Association, Inc.

Vascular Biology

Increased Uridine Adenosine Tetraphosphate Concentrations in Plasma of Juvenile Hypertensives

Vera Jankowski; Andreas-Alexander Meyer; Peter Schlattmann; Yu Gui; Xi-long Zheng; Irini Stamcou; Kristina Radtke; Thi Nguyet Anh Tran; Markus van der Giet; Markus Tölle; Walter Zidek; Joachim Jankowski

From the Medizinische Klinik Iv (CBF) (V.J., X.Z., I.S., T.N.A.T., M.v.d.G., M.T., W.Z., J.J.), Charité-University Of Berlin, Germany; the Division Of Paediatric Cardiology And Intensive Care (A.A.M., K.R.), Child Hospital, University Of Rostock, Germany; the Institute For Biometry (Ccm) (P.S.), Charité-University Of Berlin, Germany; and the Department of Biochemistry And Molecular Biology (Y.G.), University Of Calgary, Calgary, Canada.

Correspondence to Pd Dr J. Jankowski, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik IV, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail Joachim.Jankowski{at}charite.de

Background— Uridine adenosine tetraphosphate (Up₄A) was been recently characterized as a potent vasoconstrictor. Up₄A occurs in plasma from healthy subjects at concentrations sufficient to cause strong vasoconstrictive effects. In this study, Up₄A concentrations in plasma from juvenile hypertensives and normotensives were determined.

Methods and Results— Up₄A was purified to homogeneity by preparative reverse phase high performance liquid-chromatography (HPLC), affinity chromatography HPLC, and analytic reverse phase HPLC from deproteinized plasma of juvenile hypertensives and normotensives. Mean total plasma Up₄A concentration was significantly increased in juvenile hypertensives compared with juvenile normotensives (33.0±25.4 versus 3.7±0.9 nmol/L; mean±SEM, n=40 and 38, respectively; P<0.005). Accordingly, Up₄A showed a significant association with juvenile hypertension (OR for ln(Up₄A): 1.82; 95% CI 1.12, 2.95). Plasma Up₄A concentrations correlated with left ventricular mass (Kendall- correlation coefficient 0.220, n=40; P<0.05) and intima media wall thickness (Kendall- correlation coefficient 0.296, n=40; P<0.05) in the hypertensives. Because the increased intima media thickness may be related to proliferative effects of Up₄A, we studied the effects of Up₄A on human vascular smooth muscle cell proliferation. The maximum proliferative effect of Up₄A was 80.0±24.0% % above control (P<0.01). The proliferative effect of Up₄A on smooth muscle cells is cell cycle–dependent, involving stimulation of S phase entry.

Conclusion— Circulating levels of Up₄A are strongly associated with juvenile hypertension. The endothelium-derived vasoconstrictor Up₄A may contribute to the early development of primary hypertension and is moreover an important risk factor of juvenile hypertension.

This study describes the association of circulating levels of Up₄A with juvenile hypertension. Up₄A concentration correlated with blood pressure, intima media wall thickness, and left ventricular mass.

Key Words: uridine adenosine tetraphosphate • hypertension • plasma concentration • proliferation

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