Increased uridine adenosine tetraphosphate concentrations in plasma of juvenile hypertensives.
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.


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.


CONCLUSIONS
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.
Jankowski
Vera
V
Medizinische Klinik IV, Charité-University of Berlin, Germany.
Meyer
Andreas-Alexander
AA
Schlattmann
Peter
P
Gui
Yu
Y
Zheng
Xi-long
XL
Stamcou
Irini
I
Radtke
Kristina
K
Tran
Thi Nguyet Anh
TN
van der Giet
Markus
M
Tölle
Markus
M
Zidek
Walter
W
Jankowski
Joachim
J
D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001795:Blood Pressure Determination; D002318:Cardiovascular Diseases / Q000517:prevention & control; D016022:Case-Control Studies; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D018450:Disease Progression; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000175:diagnosis* / Q000201:enzymology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012737:Sex Factors; D014529:Uridine / Q000097:blood* / Q000378:metabolism
D015415:Biomarkers; D014529:Uridine