标题：
The role of platelet in the development of salt-sensitive hypertension via high-salt induced inflammation.
讲者：
毛红亚
单位：
中国医学科学院医学实验动物研究所
播放：
2050
论文摘要：
ABSTRACT
PURPOSE: High salt intake has been known to cause hypertension
and end-organ damages. In recent years, increasing clinical and experimental
studies indicate that inflammation acts as a key factor in the progress of
salt-sensitive hypertension. It was found that the high-salt diet increased
blood pressure and markedly increased the amount of Ca2+ in
platelet, and the abnormal platelet function in Dahl salt-hypertensive rats.
The expression of P-selectin, a marker for platelet activation, is higher in
salt-sensitive hypertensives than salt-resistant patients. We hypothesize that high
salt intake increases Ca2+ concentration in platelet via sodium-hydrogen
exchanger isoform-1 (NHE-1) on the membrane of platelet, to activate platelets.
The activated platelets trigger variety of inflammatory reactions contributing
to the progress of slat-sensitive hypertension.
Methods:
After blood pressure was stabilized for one week, male
Dahl salt-sensitive (Dahl/SS) rats and salt-resistant control
(SS-13BN) rats were fed with low-salt (0.12%NaCl) and high-salt
(8%NaCl) diet respectively for four weeks. Systolic and diastolic blood
pressures were measured by tail-cuff method once a week. Animals were sacrificed
and peripheral blood was isolated via abdominal aorta for detection of platelet
p-selectin, NHE-1 and [Ca2+]i by flow cytometry. The inflammation
factors expression in kidney was checked by immunohistochemistry and western
blotting. To test the role of NHE-1 in the activation of platelet by high salt
stimulation, the P-selectin expression and Ca2+ concentration were
measured in isolated platelets from male Sprague Dawley rats treated with
sodium and NHE-1 inhibitor HOE642.
Results: High salt diet increased systolic, diastolic and mean blood pressures in
Dahl/SS rats with increased the expression of P-selectin and NHE1 expression in
the membrane and Ca2+ concentration in cytosol of platelet, but not
in SS-13BN rats. The increased expression of P-selectin and NCX
(sodium-calcium exchanger) in the membrane and Ca2+ concentration in
cytosol in isolated platelet stimulated by high salt were prevented by NHE-1
inhibitor HOE642. High salt diet results in signi?cant in?ltration of CD45+
leukocytes, and increased expression of IL-6, IL-1, NF-κB in the kidney that is
accompanied by the development of hypertension in Dahl/SS rats, but not in
SS-13BN rats.
Conclusion: These findings
suggest that platelet activation via NHE-1 is involved in the development of
salt-sensitive hypertension by inducing inflammation response, which may help
to elucidate a new mechanism, and provide an important reference for treatment
and prevention of salt-sensitive hypertension.
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