Paper Information

Title: 

MECHANISM OF CHRONIC ANTI-DIURETIC EFFECT OF BENDROFLUMETHIAZIDE IN RATS WITH LITHIUM INDUCED NEPHROGENIC DIABETES INSIPIDUS

Type: POSTER
Author(s): KARIMI ZEYNAB*,SHID MOUSAVI SEYED MOSTAFA,DEHGHANI GH.A.
 
 *DEPARTMENT OF PHYSIOLOGY, SCHOOL OF MEDICINE, SHIRAZ UNIVERSITY OF MEDICAL SCIENCES, SHIRAZ, IRAN
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2009Volume 19
 
 
Abstract: 

The present study has aimed to determine the mechanism of paradoxical antidiuretic effect of thiazides at long-term in rats with nephrogenic diabetes insipidus (NDI). Initially, bilateral renal denervation (DNX) was done in half of the rats. To induce NDI, all rats were given food containing LiCL (40-60mmol/kg) for about one mouth. After induction of NDI, bendroflumethiazide (BFTZ) at 9 mg/day or distilled water as its vehicle were given through triple gavages in a day to rats with DNX (NDI/DNX+BFTZ or NDI/DNX+V groups) and without DNX (NDI+BFTZ or NDI+V groups) for 10 days. In all animals, urine was collected in metabolism cage for six hours and then an arterial blood sample was taken and systolic blood pressure was measured from tail at one day before (D0), and days of one (D1), five (D5) and ten (D10) after starting administration of BFTZ or its vehicle. Approximately equally in NDI+BFTZ and NDI/DNX+BFTZ groups, the amounts of creatinine, lithium, osmolar and free-water clearances were decreased (all P<0.01), but the levels of urine osmolality, fractional proximal water reabsorption, and fractional distal water reabsorption were increased (all P<0.001) at D1 with respect to D0, and all of them remained at about the same levels of D1 in D5 and D10. Chronic antiduiretic effect of BFTZ was exerted through both its direct ADH-like action at distal parts of nephron to increase free-water reabsorption, and its indirect effect of reducing extracellular volume, which led to decrease in glomerular filtrationand increase of proximal tubular reabsorption, without the need to renal sympathetic nerves.

 
Keyword(s): BENDROFLUMETHIAZIDE, ANTI-DIURETIC EFFECT, NDI
 
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