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Article: Action of thiazide on renal interstitial calcium.

Eley, Shaleka L / Allen, Crystal M / Williams, Cicely L / Bukoski, Richard D / Pointer, Mildred A

American journal of hypertension

2008  Volume 21, Issue 7, Page(s) 814–819

Abstract: ... used thiazide, may be the result of increased interstitial fluid calcium as a consequence of decreased ... 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 ...

Abstract 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.
MeSH term(s) Animals ; Antihypertensive Agents/pharmacology ; Blood Pressure/drug effects ; Calcium/metabolism ; Calcium/urine ; Diuretics/pharmacology ; Extracellular Fluid/metabolism ; Hydrochlorothiazide/pharmacology ; Hypertension/drug therapy ; Hypertension/etiology ; Hypertension/metabolism ; Hypertension/physiopathology ; Kidney Cortex/drug effects ; Kidney Cortex/metabolism ; Kidney Cortex/physiopathology ; Male ; Rats ; Rats, Inbred Dahl ; Sodium Chloride, Dietary ; Time Factors
Chemical Substances Antihypertensive Agents ; Diuretics ; Sodium Chloride, Dietary ; Hydrochlorothiazide (0J48LPH2TH) ; Calcium (SY7Q814VUP)
Language English
Publishing date 2008-05-01
Publishing country United States
Document type Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID 639383-4
ISSN 1879-1905 ; 0895-7061
ISSN (online) 1879-1905
ISSN 0895-7061
DOI 10.1038/ajh.2008.158
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