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Diuretic effects on cardiac hypertrophy in the stroke prone spontaneously hypertensive rat.

Contard F, Glukhova M, Marotte F, Narcisse G, Schatz C, Swynghedauw B, Guez D, Samuel JL, Rappaport L.

U127 INSERM, Hopital Lariboisiere, Paris, France.

OBJECTIVE: The aim was to compare the effects of two diuretics, indapamide and hydrochlorothiazide, on cardiac hypertrophy in stroke prone spontaneously hypertensive rats (SHR-SP). METHODS: Six week old SHR-SP, on a 1% sodium chloride water intake, were treated with oral indapamide (3 mg.kg-1 x d-1) or hydrochlorothiazide (20 mg.kg-1 x d-1) over a 44 d period. The hypertrophic process was evaluated by classical indices and by the morphological analysis of myocyte cross sectional area, coronary artery thickness, and immunohistochemical analysis of interstitial fibrosis. RESULTS: In the untreated SHR-SP on 1% sodium chloride, all animals developed severe hypertension and cardiac hypertrophy when compared to normotensive salt loaded WKY by 13 weeks of age. In salt loaded SHR-SP treated with indapamide or hydrochlorothiazide, systolic blood pressure was moderately decreased by the end of the treatment when compared with untreated SHR-SP, at 259(7) and 245(7) mm Hg respectively, v 300(11) mm Hg, p < or = 0.05. Myocyte enlargement appears to be the main feature involved in the development of cardiac hypertrophy in the SHR-SP. By the end of treatment both indapamide and hydrochlorothiazide prevented the development of cardiac hypertrophy evaluated by heart weight to body weight ratio [4.69(0.07) and 4.61(0.08) respectively, v 5.39(0.13), p < or = 0.001] and myocyte hypertrophy (-33% and -21% of the SHR-SP values, p < or = 0.001). Myocardial interstitial fibrosis and perivascular fibrosis were practically absent in the two treated groups. CONCLUSIONS: Our results allow the characterisation of SHR-SP cardiac hypertrophy and indicate that the two types of chronic diuretic treatment prevent SHR-SP cardiac hypertrophy with a drug specific efficiency.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8490943&dopt=Abstract hydrochlorothiazide Microzide



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[Effect of hydrochlorothiazide on calcium metabolism in postoperative hypoparathyroidism]

[Article in Polish]

Sawicki A.

Kliniki Endokrynologii CMKP w Warszawie.

Vitamin D3 administered to patients with postoperative hypoparathyroidism increases calcium absorption from the gut and calcium blood levels but leads to hypercalciuria and may produce renal lithiasis. Thiazides decrease calcium excretion with the urine. Therefore, an effect of combined therapy with hydrochlorothiazide, vitamin D3 and calcium on hypoparathyroidism was investigated. Twenty one women were selected out of 135 patients with postoperative hypoparathyroidism. These women were constantly given vitamin D3 (30,000-225,000 IU daily) and calcium. Normocalcemia, hyperphosphatemia and hypercalciuria were noted before the treatment with hydrochlorothiazide. Therapy normalized hypercalciuria but did not change mean differences in calcemia, phosphatemia, magnesemia, blood alkaline phosphatase and phosphates and magnesium clearance factors. Hypercalcemia and necessity to withdraw hydrochlorothiazide together with change of either doses or preparation of vitamin D3 were noted in three patients, including one patient in whom both hypercalcemia and hypercalciuria with the symptoms of vitamin D3 poisoning were observed. The author suggests that combined therapy with hydrochlorothiazide, vitamin D3 and calcium prevents hypercalciuria but may require changes in vitamin D3 dosage and withdrawal of hydrochlorothiazide in some patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1962853&dopt=Abstract hydrochlorothiazide Microzide



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Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma by liquid chromatography.

Erk N.

University of Ankara, Faculty of Pharmacy, Department of Analytical Chemistry, 06100 Tandogan, Ankara, Turkey. erk pharmacy.ankara.edu.tr

A simple, selective, sensitive and precise high-performance liquid chromatographic plasma assay for the antihypertensive drugs, irbesartan and hydrochlorothiazide is described. Good chromatographic separation was achieved using a Supelcocil C(18) (5 micrometer 15 cmx4.6 mm) column and a mobile phase consisting of 10 mM potassium dihydrogen phosphate:methanol:acetonitrile (5:80:15 v/v/v) (pH:2.5) while at a flow-rate of 1.0 ml min(-1). Irbesartan and hydrochlorothiazide were detected at 275 nm and were eluted 5.8 and 7.8 min, respectively, after injection. No endogenous substances were found to interfere. The method utilizes protein precipitation with acetonitrile as the only sample preparation involved prior to reversed-phase high-performance liquid chromatography. No internal standard was required. Linearity range for irbesartan and hydrochlorothiazide was 10.0-60.0 microgram ml(-1) and 4.0-20.0 microgram ml(-1), respectively. The determination of intra- and inter-day precision (RSD) was less than 2.5 and 3.5%, at all concentration levels, while the inter- and intra-day accuracy (% difference) was less than 4.9-6.2%. This method is being used in a therapeutic drug monitoring service to quantitate these therapeutic agents in patients for pharmacokinetic studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12504198&dopt=Abstract hydrochlorothiazide Microzide



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Is hydrochlorothiazide-induced hypocalciuria due to inhibition of prostaglandin E2 synthesis?

Calo L, Cantaro S, Marchini F, Giannini S, Castrignano R, Gambaro G, Antonello A, Baggio B, D'Angelo A, Williams H, et al.

Institute of Internal Medicine, University of Padova, Italy.

1. Since prostaglandin E2 could play a role in idiopathic hypercalciuria, and considering the well-established hypocalciuric action of hydrochlorothiazide, we have evaluated the effect of 15 days' treatment with hydrochlorothiazide in 10 hypercalciuric male stoneformers on urinary Ca2+ and prostaglandin E2, as well as on plasma bicyclo-prostaglandin E2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone. 2. In addition to lowering urinary Ca2+ (P less than 0.001), hydrochlorothiazide also promoted a significant fall in urinary prostaglandin E2 (P less than 0.001), plasma bicyclo-prostaglandin E2 (P less than 0.001) and 1,25-dihydroxyvitamin D (P less than 0.01), and an increase in plasma parathyroid hormone (P less than 0.025), whereas plasma 25-hydroxyvitamin D was unchanged. 3. A positive correlation between urinary Ca2+ and prostaglandin E2 was present before (P less than 0.00005), but not after, hydrochlorothiazide. Plasma bicyclo-prostaglandin E2 and plasma 1,25-dihydroxyvitamin D were positively correlated both before (P less than 0.005) and after (P less than 0.005) hydrochlorothiazide, as was also the percentage change in each induced by the drug (P less than 0.05). Furthermore, the changes in plasma 25-hydroxyvitamin D and plasma 1,25-dihydroxyvitamin D after hydrochlorothiazide were negatively correlated (P less than 0.05). 4. It is suggested that a block of prostaglandin E2 synthesis plays a role in the effect of hydrochlorothiazide on Ca2+ metabolism, most probably through an inhibition of 1 alpha-hydroxylase activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2156653&dopt=Abstract hydrochlorothiazide Microzide



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Effect of diuretics on cell potassium transport: an electron microprobe study.

Beck FX, Dorge A, Giebisch G, Thurau K.

Department of Physiology, University of Munich, Federal Republic of Germany.

To study the short-term uptake of potassium across the basolateral membrane into individual tubule cells, rubidium was used and measured by electron microprobe analysis. Changes of rubidium uptake were interpreted to reflect altered sodium entry and basolateral Na-K-ATPase activity. The effects of hydrochlorothiazide, amiloride and furosemide were determined in saline-loaded animals. Hydrochlorothiazide inhibited rubidium uptake in proximal convoluted and distal convoluted tubule cells. The effect was largest in distal convoluted tubule cells. Amiloride reduced rubidium uptake in principal cells as well as in proximal convoluted, distal convoluted and connecting tubule cells. Furosemide depressed rubidium uptake in distal convoluted tubule cells, but increased uptake in principal cells. Rubidium uptake into intercalated cells was not affected by any of the diuretics used. Hydrochlorothiazide and amiloride altered rubidium uptake also in cells not associated with the main diuretic action. These effects of hydrochlorothiazide and amiloride may be due to interference with cell transport mechanisms of Na-H and anion exchange.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2163464&dopt=Abstract hydrochlorothiazide Microzide