Increased uridine adenosine tetraphosphate concentrations in plasma of juvenile hypertensives.

Abstract

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-tau correlation coefficient 0.220, n=40; P<0.05) and intima media wall thickness (Kendall-tau 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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 27 Issue 8 Pg. 1776-81 (Aug 2007) ISSN: 1524-4636 [Electronic] United States
• PMID: 17569882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Uridine

Topics

• Adolescent
• Age Factors
• Biomarkers (blood)
• Blood Pressure Determination
• Cardiovascular Diseases (prevention & control)
• Case-Control Studies
• Cell Proliferation
• Chromatography, High Pressure Liquid
• Cohort Studies
• Disease Progression
• Echocardiography, Doppler
• Female
• Humans
• Hypertension (blood, diagnosis, enzymology)
• Male
• Muscle, Smooth, Vascular (pathology, physiology)
• Probability
• Reference Values
• Risk Assessment
• Sensitivity and Specificity
• Severity of Illness Index
• Sex Factors
• Uridine (blood, metabolism)