Action of thiazide on renal interstitial calcium.
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.


CONCLUSIONS
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.
Eley
Shaleka L
SL
JLC-Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, North Carolina, USA.
Allen
Crystal M
CM
Williams
Cicely L
CL
Bukoski
Richard D
RD
Pointer
Mildred A
MA
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000652:urine; D004232:Diuretics / Q000494:pharmacology*; D045604:Extracellular Fluid / Q000378:metabolism*; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary; D013997:Time Factors
D000959:Antihypertensive Agents; D004232:Diuretics; D017673:Sodium Chloride, Dietary; D006852:Hydrochlorothiazide; D002118:Calcium