噻嗪类药物对肾间质钙的作用。
Action of thiazide on renal interstitial calcium.
作者信息
Eley Shaleka L, Allen Crystal M, Williams Cicely L, Bukoski Richard D, Pointer Mildred A
机构信息
JLC-Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, North Carolina, USA.
出版信息
Am J Hypertens. 2008 Jul;21(7):814-9. doi: 10.1038/ajh.2008.158. Epub 2008 May 1.
BACKGROUND
Although thiazides increase urinary sodium excretion, they also decrease urinary calcium excretion. Recent studies in our laboratory have shown that increased dietary salt significantly reduces interstitial fluid calcium in Dahl salt-sensitive (DS) rats, and this was associated with a rise in blood pressure and increased urinary calcium excretion. Owing to the vasorelaxant actions of increased extracellular fluid calcium, we reasoned that the antihypertensive action of hydrochlorothiazide (HCTZ), a commonly used thiazide, may be the result of increased interstitial fluid calcium as a consequence of decreased urinary calcium excretion.
METHODS
To test this hypothesis, DS and Dahl salt-resistant (DR) rats were given high salt alone or in combination with HCTZ for 1 week. Renal cortical interstitial fluid calcium was determined by the zero net flux method.
RESULTS
High salt decreased cortical interstitial fluid calcium (1.69 +/- 0.25 vs. 1.13 +/- 0.05 mmol/l; P < 0.05) in DS rats as previously reported; thiazide treatment had no effect on the high salt interstitial fluid calcium response in salt-sensitive animals. However, thiazide decreased interstitial fluid calcium in DS on a normal salt diet. Cortical interstitial fluid calcium was unchanged by dietary salt in DR rats, and thiazide did not alter this interstitial fluid calcium response.
CONCLUSION
We interpret these data to mean that (i) short-term thiazide treatment does not reduce blood pressure by restoring renal cortical interstitial fluid calcium concentration and (ii) a decrease in renal cortical interstitial fluid calcium may not contribute to the increased renal vasoconstriction seen in salt-sensitivity.
背景
尽管噻嗪类药物可增加尿钠排泄，但它们也会减少尿钙排泄。我们实验室最近的研究表明，增加饮食中的盐摄入量会显著降低Dahl盐敏感（DS）大鼠的间质液钙含量，这与血压升高和尿钙排泄增加有关。由于细胞外液钙增加具有血管舒张作用，我们推测常用噻嗪类药物氢氯噻嗪（HCTZ）的降压作用可能是尿钙排泄减少导致间质液钙增加的结果。
方法
为了验证这一假设，给DS大鼠和Dahl盐抵抗（DR）大鼠单独给予高盐或联合HCTZ处理1周。采用零净通量法测定肾皮质间质液钙含量。
结果
如先前报道，高盐降低了DS大鼠的皮质间质液钙含量（1.69±0.25 vs. 1.13±0.05 mmol/l；P<0.05）；噻嗪类药物治疗对盐敏感动物的高盐间质液钙反应没有影响。然而，在正常盐饮食的DS大鼠中，噻嗪类药物降低了间质液钙含量。在DR大鼠中，饮食中的盐对皮质间质液钙含量没有影响，噻嗪类药物也没有改变这种间质液钙反应。
结论
我们对这些数据的解释是：（i）短期噻嗪类药物治疗不会通过恢复肾皮质间质液钙浓度来降低血压；（ii）肾皮质间质液钙减少可能与盐敏感性肾血管收缩增加无关。
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