title: Synergistic effects of nitric oxide and prostaglandins on renal escape from vasopressin-induced antidiuresis.
abstract: Recent results from our laboratories indicate that renal escape from AVP-induced antidiuresis is accompanied by marked downregulation of kidney aquaporin-2 (AQP2) and AVP V2 receptors. The present studies evaluated the effect of nitric oxide (NO) and PG synthesis blockade on escape from antidiuresis. dDAVP-infused rats were water loaded (WL) for 5 days. l-NAME, an NO synthesis inhibitor, or diclofenac, a cyclooxygenase inhibitor, was infused subcutaneously beginning 1 day before WL. As early as 2 days after WL, urine volume increased and urine osmolality decreased, indicating the onset of escape. Endogenous NO synthesis, measured as urinary NO2 + NO3 excretion, was significantly increased in the WL group compared with the non-WL controls during all 5 days of WL. l-NAME (20 mg. kg(-1). day(-1)) markedly decreased urine volume on days 4 and 5 of WL, indicating inhibition of the escape phenomenon. Kidney AQP2 protein was significantly increased by this dose of l-NAME as well. A lower dose of l-NAME (10 mg. kg(-1). day(-1)) or diclofenac (2.5 mg. kg(-1). day(-1)) did not significantly affect the escape phenomenon by itself, but the combination of l-NAME and diclofenac showed a marked inhibitory effect on the escape phenomenon, which was also accompanied by a significant increase in kidney AQP2 expression. These results therefore suggest that renal NO and PG both play important roles in escape from AVP-induced antidiuresis by acting synergistically to downregulate kidney AQP2 expression.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University, Washington, DC 20007, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murase
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.forename: Xiao Ying
authors.initials: XY
authors.lastname: Fang
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Verbalis
mesh_terms: D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000096:biosynthesis; D004008:Diclofenac / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects*; D004326:Drinking; D004357:Drug Synergism; D004435:Eating; D005786:Gene Expression Regulation; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood; D013997:Time Factors; D014554:Urination / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D011453:Prostaglandins; D014667:Vasopressins; D004008:Diclofenac; D009569:Nitric Oxide; D012964:Sodium; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester