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Am J Physiol Regul Integr Comp Physiol 284: R354-R362, 2003. First published October 10, 2002; doi:10.1152/ajpregu.00065.2002
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Vol. 284, Issue 2, R354-R362, February 2003

Synergistic effects of nitric oxide and prostaglandins on renal escape from vasopressin-induced antidiuresis

Takashi Murase1, Ying Tian1, Xiao Ying Fang2, and Joseph G. Verbalis1

1 Department of Medicine, Division of Endocrinology and Metabolism, and 2 Department of Medicine, Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007

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.

aquaporin-2


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