Tohoku J. Exp. Med., 2002, 197 (4)

Chronic Hyperosmolality Enhances ANP-Dependent cGMP Production via Stimulation
of Transcription and Protein Synthesis in Cultured Rat IMCD Cells

EIJI KUSANO, OSAMU IIMURA, FUJIMARO ISHIDA, TETSU AKIMOTO, MORIMASA AMEMIYA,
YASUHIRO ANDO and YASUSHI ASANO

Department of Nephrology, Jichi Medical School, Tochigi 329-0498

Recently, we found that hyperosmolality acutely inhibited atrial natriuretic peptide (ANP) dependent cGMP production by reducing ANP binding sites in cultured rat inner medullary collecting duct (IMCD) cells. Therefore, the present study was undertaken to evaluate the chronic effect of hyperosmolality on ANP dependent cGMP production in IMCD cells. Cell culture was carried out either in an iso-osmotic or hyperosmotic solution consisting of equi-isomolar NaCl and/or urea. Incubations with ANP and/or other agents were performed under the same osmotic conditions. ANP or SNP stimulated cGMP production was enhanced in a chronically hyperosmotic medium. These changes occurred in an osmolality-dependent manner. Hyperosmolality with sodium alone or with sodium and urea, but not with urea alone, was effective for the enhancement of ANP action. There was no significant difference between ¹²⁵I-ANP specific bindings under iso-osmotic and hyperosmotic conditions. Incubation with cytoskeleton modulators did not affect ANP-dependent cGMP production stimulated by hyperosmolality. On the other hand, both actinomycin D, an inhibitor of transcription, and cycloheximide, an inhibitor of protein synthesis, prevented the stimulatory effects of hyperosmolality. The results suggest that chronic hyperosmolality enhances ANP-dependent cGMP production via stimulation of transcription and protein synthesis in cultured rat IMCD cells.

Keywords —— hyperosmolality; ANP; cGMP; inner medullary collecting duct cells; protein synthesis

© 2002 Tohoku University School of Medicine

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Tohoku J. Exp. Med., 2002, 197, 209-220

Address for reprints: Eiji Kusano, M.D., Department of Nephrology, Jichi Medical School, Yakushiji 3311-1, Minamikawachi, Tochigi 329-0498, Japan.

e-mai: eishun@jichi.ac.jp