EFFECTS OF DIURETICS ON RENAL KALLIKREIN GENE EXPRESSION IN RATS

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Abstract

SUMMARY

1. To determine the effects of diuresis and changes in electrolyte balance on kallikrein gene expression, renal kallikrein mRNA levels were correlated with urine volumes, urinary electrolyte levels, haematocrit and plasma electrolyte levels in rats treated with substances with a range of diuretic activities.

2. Furosemide and related compounds, benzyl furosemide and isofurosemide, as well as amiloride hydrochloride, chlorothiazide or the vehicle (saline) were administered twice daily for 24 or 72 h to rats housed in metabolic cages.

3. Diuresis occurred after each treatment with furosemide, after the initial treatment with benzyl furosemide and did not occur after isofurosemide, amiloride hydrochloride or chlorothiazide.

4. Kallikrein gene expression in kidney was increased after 72 h treatment with furosemide, after 24 or 72 h treatment with benzyl furosemide or amiloride hydrochloride and was unchanged after 24 or 72 h treatment with isofurosemide or chlorothiazide, compared with vehicle-treated controls.

5. Plasma urea levels were elevated after 72 h treatment with furosemide, benzyl furosemide and chlorothiazide and plasma chloride was decreased after 24 and 72 h benzyl furosemide. Haematocrits were unchanged. There were no changes in urinary electrolyte levels 72 h after treatment with any of the diuretics.

6. Neither diuresis nor measurable changes in plasma or urinary electrolytes correlate with changes in renal kallikrein gene expression after diuretic treatment of rats.

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