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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
DIFFERENTIAL ACTION OF AMILORIDE IN HUMAN EX VIVO ENDOTHELIUM
Abstract number: O62
Drüppel
1
*V.
, Lenders
2
M., Schmitz B., Oberleithner
1
H., Brand
2
E., Kasprzak
4
B., Brand
3
S.-M., Kusche-Vihrog
1
K.
1
University of Münster, Institute of Physiology II, Münster, Germany
2
University Hospital Münster, Internal Medicine D, Münster, Germany
3
University Hospital Münster, Institute of Sports Medicine, Münster, Germany
4
University Hospital Münster, Vascular and Endovascular Surgery, Münster, Germany
The diuretic amiloride blocks the epithelial sodium channel (ENaC) in kidney epithelia, but also in vascular endothelium, where it leads to a decrease in cortical cell stiffness and an increase of the vasodilator nitric oxide. In the current clinical setting, we study a possible correlation of endothelial function, arterial stiffness and genetic predisposition.
Human side branches (A. femoralis) were prepared and cultured (1nM aldosterone) for ex vivo endothelial cell stiffness measurements using atomic force microscopy. Amiloride (5µM) was acutely administered for 30 minutes. Pulse wave velocity (PWV) was used as clinical indicator for the degree of overall arterial stiffness. DNA for genotyping was extracted from EDTA blood samples.
Confirming cell culture studies, 55% of the samples responded with a softening of the endothelial cell cortex after amiloride treatment. Most interestingly, we also detected paradox effects, as 17% of the patients ex vivo endothelium stiffened after in vitro drug administration or did not respond to amiloride (28%). These paradox amiloride effects were observed more often in older patients (p=0.046) and correlated with high PWV-values (p=0.0126). A single nucleotide polymorphism within the mineralocorticoid receptor (NR3C2) was also associated with increased PWV (p=0.0072) in that the minor allele increased PWV by 2.4 m/s.
The observed differential action of amiloride is in line with clinical observations that patients differentially respond to antihypertensive treatment, which might also be explained by hitherto unknown genetic factors. Identification of these predisposing factors may help understanding interindividually different evolution of vascular disease and developing more individually tailored treatment strategies.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :O62