title: Cooperative mechanisms involved in chronic antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus.
abstract: Previous studies of central diabetes insipidus suggested that thiazides acutely exerted a paradoxical antidiuresis by either indirectly activating volume-homeostatic reflexes to decrease distal fluid-delivery, or directly stimulating distal water-reabsorption. This study investigated whether the direct and indirect actions of bendroflumethiazide (BFTZ) simultaneously cooperated and also whether the renal nerves were involved in inducing long-term antidiuresis in nephrogenic diabetes insipidus (NDI). BFTZ or vehicle was gavaged into bilateral renal denervated and innervated rats with lithium-induced NDI for 10 days, constituting four groups. At one day before (D0) and one, five and ten days after starting administration of BFTZ or vehicle, rats were placed in metabolic cages to collect urine for 6 hours. BFTZ-treatment in both renal innervated and denervated rats caused equivalent reductions in urine-flow, creatinine clearance, lithium clearance and free-water clearance, but rises in urine-osmolality, fractional proximal reabsorption and fractional distal reabsorption at all days compared to D0, as well as to those of their relevant vehicle-received group. Therefore, the chronic antidiuretic response to BFTZ in conscious NDI rats was exerted through a concomitant cooperation of its direct distal effect of stimulating water-reabsorption and its indirect effect of reducing distal fluid-delivery by activating volume-homeostatic mechanisms, which appeared independent of the renal nerves.
authors.affiliation: Shiraz University of Medical Sciences Department of Physiology, School of Medicine Shiraz 71365-1689 Iran.
authors.forename: S M S
authors.initials: SM
authors.lastname: Moosavi
authors.affiliation: Shiraz University of Medical Sciences Department of Physiology, School of Medicine Shiraz 71365-1689 Iran.
authors.forename: Z
authors.initials: Z
authors.lastname: Karimi
mesh_terms: D000818:Animals; D050034:Antidiuretic Agents / Q000494:pharmacology*; D017763:Autonomic Denervation; D001539:Bendroflumethiazide / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D018500:Diabetes Insipidus, Nephrogenic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects*; D004326:Drinking / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D018021:Lithium Chloride; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014563:Urodynamics / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D050034:Antidiuretic Agents; D015415:Biomarkers; D001539:Bendroflumethiazide; D003404:Creatinine; D018021:Lithium Chloride
keywords: antidiuresis; bendroflumethiazide; diabetes insipidus; lithium; lithium clearance; nephrogenic diabetes insipidus; thiazide diuretics